Systemic lupus erythematosus in a multiethnic US cohort LUMINA (XLI): factors predictive of self‐reported work disability

PubMed Central

Bertoli, A M; Fernández, M; Alarcón, G S; Vilá, L M; Reveille, J D

2007-01-01

Objective To examine the risk factors for self‐reported work disability in patients from the LUpus in MInorities: NAture vs. Nurture cohort with systemic lupus erythematosus (SLE). Methods Patients with SLE of Hispanic (Texas and Puerto Rico), African American and Caucasian ethnicity were studied. Work disability was defined by patients' self‐report. Only patients known to be employed at the baseline visit were included. The probabilities of self‐reporting work disability over time were examined by the Kaplan–Meier method; differences between ethnic groups were examined by the log‐rank test. The relationship of baseline socioeconomic–demographic, clinical, behavioural and psychological features with work disability was examined by standard statistical tests. Variables with p⩽0.10 in these analyses were examined by logistic regression. Results The rate of self‐reported work disability among the 273 patients studied was 19% at 5 years; it was numerically higher for the African Americans (25%) than for the Hispanics from Texas (19%) and the Caucasians (18%). The rate for the Hispanics from Puerto Rico was 7% at 2 years; 5‐year rates could not be estimated for this ethnic subgroup (shorter follow‐up in the cohort). In the regression analysis, age, male sex, poverty, total disease duration, disease activity and damage accrual were predictors of work disability. Conclusions The rate of work disability was 19% at 5 years. Patients with SLE with more severe disease and with lower socioeconomic status are at high risk of becoming disabled. The toll SLE imposes could possibly be reduced in patients at risk if, in addition to medical treatment, services needed to overcome their disadvantageous socioeconomic status are provided. PMID:16815862

Predictive factors of flares in systemic lupus erythematosus patients: data from a multiethnic Latin American cohort.

PubMed

Ugarte-Gil, M F; Wojdyla, D; Pastor-Asurza, C A; Gamboa-Cárdenas, R V; Acevedo-Vásquez, E M; Catoggio, L J; García, M A; Bonfá, E; Sato, E I; Massardo, L; Pascual-Ramos, V; Barile, L A; Reyes-Llerena, G; Iglesias-Gamarra, A; Molina-Restrepo, J F; Chacón-Díaz, R; Alarcón, G S; Pons-Estel, B A

2018-04-01

Purpose The purpose of this paper is to determine the factors predictive of flares in systemic lupus erythematosus (SLE) patients. Methods A case-control study nested within the Grupo Latino Americano De Estudio de Lupus (GLADEL) cohort was conducted. Flare was defined as an increase ≥4 points in the SLEDAI. Cases were defined as patients with at least one flare. Controls were selected by matching cases by length of follow-up. Demographic and clinical manifestations were systematically recorded by a common protocol. Glucocorticoid use was recorded as average daily dose of prednisone and antimalarial use as percentage of time on antimalarial and categorized as never (0%), rarely (>0-25%), occasionally (>25%-50%), commonly (˃50%-75%) and frequently (˃75%). Immunosuppressive drugs were recorded as used or not used. The association between demographic, clinical manifestations, therapy and flares was examined using univariable and multivariable conditional logistic regression models. Results A total of 465 cases and controls were included. Mean age at diagnosis among cases and controls was 27.5 vs 29.9 years, p = 0.003; gender and ethnic distributions were comparable among both groups and so was the baseline SLEDAI. Independent factors protective of flares identified by multivariable analysis were older age at diagnosis (OR = 0.929 per every five years, 95% CI 0.869-0.975; p = 0.004) and antimalarial use (frequently vs never, OR = 0.722, 95% CI 0.522-0.998; p = 0.049) whereas azathioprine use (OR = 1.820, 95% CI 1.309-2.531; p < 0.001) and SLEDAI post-baseline were predictive of them (OR = 1.034, 95% CI 1.005-1.064; p = 0.022). Conclusions In this large, longitudinal Latin American cohort, older age at diagnosis and more frequent antimalarial use were protective whereas azathioprine use and higher disease activity were predictive of flares.

What have we learned from a 10-year experience with the LUMINA (Lupus in Minorities; Nature vs. nurture) cohort? Where are we heading?

PubMed

Uribe, América G; McGwin, Gerald; Reveille, John D; Alarcón, Graciela S

2004-06-01

Recently, there has been an awareness of the variable phenotypic expression of numerous disorders between individuals from different ethnicities, systemic lupus erythematosus (SLE) one of them. These disparities probably arise from the interaction between genetic and non-genetic (environmental, socioeconomic-demographic, cultural and behavioral) factors. To delineate the influence of these factors on SLE outcome, we established a multiethnic (Hispanic, African American and Caucasian) United States (US) early cohort (<5 years disease duration). Ten years later, interesting data have emerged from the LUMINA (Lupus in Minorities: Nature vs. nurture) cohort. For example, African Americans and Hispanics from Texas have a more severe disease than Caucasians and Hispanics from Puerto Rico. Lack of private insurance, acute SLE onset, expression of HLA-DRB1*01 (DR1) and C4A*3 alleles were associated with higher disease activity, whereas age, the number of American College of Rheumatology criteria met, disease activity, corticosteroid use and abnormal illness behaviors were consistent predictors of damage. In turn, damage and poverty were found to predict mortality. We now plan to apply new approaches (genetic admixture) to deconfound the complex interaction between genetic and non-genetic factors influencing SLE outcome. These data may have impact on the development of policies aimed at eliminating health disparities in the US.

The effect of race on incidence and clinical course in systemic lupus erythematosus: The Hopkins Lupus Cohort.

PubMed

Petri, M

1998-01-01

Systemic lupus erythematosus, a chronic autoimmune disease of young women, has a higher incidence and prevalence in African Americans. The Hopkins Lupus Cohort, a prospective longitudinal study of SLE outcomes, has shown that race is a major predictor of clinical manifestations, laboratory and serologic tests, and disease-related morbidity. The effect of race on musculoskeletal morbidity remains even after adjustment for education, insurance status, and smoking.

Comparison of ethnicity, gender, age of onset and outcome in South Africans with systemic lupus erythematosus.

PubMed

Budhoo, A; Mody, G M; Dubula, T; Patel, N; Mody, P G

2017-04-01

Ethnicity, gender and age of onset are reported to influence the expression and outcome of systemic lupus erythematosus. We studied a multi-ethnic cohort of 408 South Africans (91.2% females) comprising 237 (58.1%) Indians, 137 (33.6%) African Blacks, 17 (4.2%) Mixed ethnicity and 17 (4.2%) Whites. The most common manifestations were arthritis (80.6%), photosensitivity (67.2%), oral ulcers (50.0%), malar rash (49.0%) and renal (39.2%). The common laboratory findings were positive anti-nuclear factor (96.8%), haematological (74.8%) and anti-dsDNA antibodies (45.3%). Serositis ( p = 0.002), nephritis ( p = 0.039), leucopaenia ( p = 0.001), haemolytic anaemia ( p = 0.026), anti-dsDNA antibodies ( p = 0.028) and anti-Sm antibodies ( p = 0.050) were more common in African Blacks compared to Indians. Males had increased prevalence of discoid rash ( p = 0.006) and anti-Sm antibodies ( p = 0.016). Discoid rash ( p = 0.018), renal involvement ( p < 0.001), psychosis ( p = 0.028), seizures ( p = 0.020), anti-dsDNA antibodies ( p = 0.009), leucopaenia ( p = 0.006), haemolytic anaemia ( p = 0.017) and thrombocytopaenia ( p = 0.023) were more common with early-onset systemic lupus erythematosus. On multivariate analysis, the independent predictors of death were renal involvement, anti-dsDNA antibodies and seizures. There were 53 (13%) deaths and the five- and 10-year survival was 90.8% and 85.7% respectively, with no differences related to ethnicity or age of onset. In conclusion, we report on the spectrum and outcome of systemic lupus erythematosus in a large South African multi-ethnic cohort.

The Sarawak lupus cohort: clinical features and disease patterns of 633 SLE patients in a single tertiary centre from East Malaysia.

PubMed

Teh, C L; Ling, G R; Aishah, Wan Sharifah

2015-01-01

Systemic lupus erythematosus (SLE) has been well studied in West Malaysian populations but lacking in East Malaysian populations. The aim of this study was to examine the clinical features and disease patterns of patients with SLE in a multiethnic East Malaysian population in Sarawak. All SLE patients who were treated in Sarawak General Hospital were reviewed in a retrospective longitudinal study using a standard protocol from 1 January 2006 to 31 December 2013. There were a total of 633 patients in our study with the female to male ratio of 12:1. Our study patients were of multiethnic origins with predominant Chinese ethnic group. They had a mean age of 36.9 ± 13.2 years and a mean duration of illness of 7.2 ± 6.0 years. The main involvements were haematological (74.2 %), malar rash (64.0 %) and renal (58.6 %). Chinese patients were less likely to have discoid lupus, pleuritis and pericarditis, while Malay patients were more likely to have arthritis. Bidayuh patients were more likely to have oral ulcer. Secondary antiphospholipid syndrome was more common in Chinese. The majority of patients were in clinical remission with low SDI. There were 58 deaths (9.2 %) during 2006-2013 with the main causes of death being flare of disease and infection.

Systemic lupus erythematosus in the multiethnic Malaysian population: disease expression and ethnic differences revisited.

PubMed

Jasmin, R; Sockalingam, S; Cheah, T E; Goh, K J

2013-08-01

Ethnic differences in systemic lupus erythematosus (SLE) have been previously described in the multiethnic Malaysian population. However, there have since been many demographic and socioeconomic changes in the country. The aim of this study is to re-examine the clinical and immunological profiles of Malaysian SLE patients of different ethnic backgrounds. Consecutive follow-up patients at the University Malaya Medical Centre (UMMC) from July 2010 until March 2011 were included in the study. The most common clinical manifestations were malar rash (61.3%), arthritis (52.3%), haematological disease (51.6%), oral ulcers (51%) and renal disease (40.6%). Ethnic Indians had fewer malar and discoid rashes but were at higher risk of arthritis, serositis, renal and neuropsychiatric disease compared to Malays and Chinese Malaysians. Antiphospholipid syndrome (APS) was less common in Chinese. A longer duration of SLE correlated with a lower SLEDAI score. Overall, the spectrum disease expression was similar to the earlier Malaysian study but the frequency of the more severe disease manifestations, viz. renal, haematological, neuropsychiatric involvements and serositis, were lower. This study further emphasises differences primarily between ethnic Indians and the other races in Malaysia.

Associations of B cell-activating factor (BAFF) and anti-BAFF autoantibodies with disease activity in multi-ethnic Asian systemic lupus erythematosus patients in Singapore.

PubMed

Howe, H S; Thong, B Y H; Kong, K O; Chng, H H; Lian, T Y; Chia, F L; Tay, K S S; Lau, T C; Law, W G; Koh, E T; Leung, B P

2017-09-01

To measure the levels of B cell-activating factor (BAFF) and endogenous anti-BAFF autoantibodies in a cohort of multi-ethnic Asian systemic lupus erythematosus (SLE) patients in Singapore, to determine their correlation with disease activity. Serum samples from 121 SLE patients and 24 age- and sex-matched healthy controls were assayed for BAFF and anti-BAFF immunoglobulin (Ig)G antibody levels by enzyme-linked immunosorbent assay (ELISA). The lowest reliable detection limit for anti-BAFF-IgG antibody levels was defined as 2 standard deviations (s.d.) from blank. Correlation of serum BAFF and anti-BAFF IgG levels with disease activity [scored by SLE Activity Measure revised (SLAM-R)], and disease manifestations were determined in these 121 patients. SLE patients had elevated BAFF levels compared to controls; mean 820 ± 40 pg/ml and 152 pg ± 45/ml, respectively [mean ± standard error of the mean (s.e.m.), P < 0·01], which were correlated positively with anti-dsDNA antibody levels (r = 0·253, P < 0·03), and SLAM-R scores (r = 0·627, P < 0·01). In addition, SLE patients had significantly higher levels of anti-BAFF IgG, which were correlated negatively with disease activity (r = -0·436, P < 0·01), levels of anti-dsDNA antibody (r = -0·347, P < 0·02) and BAFF (r = -0·459, P < 0·01). The majority of patients in this multi-ethnic Asian SLE cohort had elevated levels of BAFF and anti-BAFF antibodies. Anti-BAFF autoantibody levels correlated negatively with clinical disease activity, anti-dsDNA and BAFF levels, suggesting that they may be disease-modifying. Our results provide further information about the complexity of BAFF pathophysiology in different SLE disease populations and phenotypes, and suggest that studies of the influence of anti-cytokine antibodies in different SLE populations will be required when selecting patients for trials using targeted anti-cytokine therapies. © 2017 British Society for

The frequency of and associations with hospitalization secondary to lupus flares from the 1000 Faces of Lupus Canadian cohort.

PubMed

Lee, J; Peschken, C A; Muangchan, C; Silverman, E; Pineau, C; Smith, C D; Arbillaga, H; Zummer, M; Clarke, A; Bernatsky, S; Hudson, M; Hitchon, C; Fortin, P R; Pope, J E

2013-11-01

Hospitalization is a major factor in health care costs and a surrogate for worse outcomes in chronic disease. The aim of this study was to determine the frequency of hospitalization secondary to lupus flare, the causes of hospitalization, and to determine risk factors for hospitalization in patients with systemic lupus erythematosus (SLE). Data were collected as part of the 1000 Canadian Faces of Lupus, a prospective cohort study, where annual major lupus flares including hospitalizations were recorded over a 3-year period. Of 665 patients with available hospitalization histories, 68 reported hospitalization related to a SLE flare over 3 years of follow-up. The average annual hospitalization rate was 7.6% (range 6.6-8.9%). The most common reasons for hospitalization were: hematologic (22.1%), serositis (20.6%), musculoskeletal (MSK) (16.2%), and renal (14.7%). Univariate risk factors for lupus hospitalization included (OR [95% CI]; p < 0.05): juvenile-onset lupus (2.2 [1.1-4.7]), number of ACR SLE criteria (1.4 [1.1-1.7], baseline body mass index (BMI) (1.1 [1.0-1.1]), psychosis (3.4 [1.2-9.9]), aboriginal race (3.2 [1.5-6.7]), anti-Smith (2.6 [1.2-5.4]), erythrocyte sedimentation rate >25 mm/hr (1.9 [1.1-3.4]), proteinuria >0.5 g/d (4.2 [1.9-9.3], and SLAM-2 score (1.1 [1.0-1.2]). After multivariate regression only BMI, number of ACR criteria, and psychosis were associated with hospitalization for lupus flare. The mean annual rate of hospitalization attributed to lupus was lower than expected. Hematologic, serositis, MSK and renal were the most common reasons. In a regression model elevated BMI, more ACR criteria and psychosis were associated with hospitalization.

Contributions of Familial Rheumatoid Arthritis or Lupus and Environmental Factors to Risk of Rheumatoid Arthritis in Women: a Prospective Cohort Study

PubMed Central

Sparks, Jeffrey A.; Chen, Chia-Yen; Hiraki, Linda T.; Malspeis, Susan; Costenbader, Karen H.; Karlson, Elizabeth W.

2014-01-01

Objective We assessed the contributions of familial rheumatoid arthritis (RA) or lupus and environmental factors to risk of RA. Methods Among 121,700 women in the Nurses’ Health Study, 65,457 provided data on familial RA/lupus. Among these, 493 RA cases (301 seropositive and 192 seronegative) were validated. We estimated hazard ratios (HR) for RA comparing those with and without familial RA/lupus, adjusting for environmental factors (smoking, alcohol, body mass index [BMI], parity, breastfeeding, menopause, hormone use, early menarche, and menstrual regularity) using Cox proportional hazards models. Population attributable risks (PAR) for RA within this cohort were calculated for familial RA/lupus, smoking, alcohol, BMI, parity, and breastfeeding. Results Familial RA/lupus was significantly associated with RA (HR 3.67), seropositive RA (HR 3.90) and seronegative RA (HR 3.95). After adjusting for environmental factors, familial RA/lupus was significantly associated with RA (HR 3.59, 95% confidence interval 2.94–4.37). Smoking >10 pack-years, alcohol intake 5–10 g/day, overweight, breastfeeding ≥12 months, and pre-menopausal status remained significantly associated with RA after adjusting for familial RA/lupus. For RA in this cohort, the PAR for smoking, BMI, alcohol, parity, or breastfeeding collectively was 41%; the PAR due to heredity from familial RA/lupus was 21%. Conclusion In this large, prospective cohort, women with familial RA/lupus had a four-fold increased risk for RA that remained significant after adjusting for environmental factors. A large proportion of RA risk was attributable to environmental factors even among those with familial RA/lupus. PMID:25103278

A Multiethnic Cohort in Hawaii and Los Angeles: Baseline Characteristics

PubMed Central

Kolonel, Laurence N.; Henderson, Brian E.; Hankin, Jean H.; Nomura, Abraham M.Y.; Wilkens, Lynne R.; Pike, Malcolm C.; Stram, Daniel O.; Monroe, Kristine R.; Earle, Maj E.; Nagamine, Faye S.

2015-01-01

The authors describe the design and implementation of a large multiethnic cohort established to study diet and cancer in the United States. They detail the source of the subjects, sample size, questionnaire development, pilot work, and approaches to future analyses. The cohort consists of 215,251 adult men and women (age 45–75 years at baseline) living in Hawaii and in California (primarily Los Angeles County) with the following ethnic distribution: African-American (16.3%), Latino (22.0%), Japanese-American (26.4%), Native Hawaiian (6.5%), White (22.9%), and other ancestry (5.8%). From 1993 to 1996, participants entered the cohort by completing a 26-page, self-administered mail questionnaire that elicited a quantitative food frequency history, along with demographic and other information. Response rates ranged from 20% in Latinos to 49% in Japanese-Americans. As expected, both within and among ethnic groups, the questionnaire data show substantial variations in dietary intakes (nutrients as well as foods) and in the distributions of non-dietary risk factors (including smoking, alcohol consumption, obesity, and physical activity). When compared with corresponding ethnic-specific cancer incidence rates, the findings provide tentative support for several current dietary hypotheses. As sufficient numbers of cancer cases are identified through surveillance of the cohort, dietary and other hypotheses will be tested in prospective analyses. PMID:10695593

Features associated with, and the impact of, hemolytic anemia in patients with systemic lupus erythematosus: LX, results from a multiethnic cohort.

PubMed

Durán, Sergio; Apte, Mandar; Alarcón, Graciela S; Marion, Miranda C; Edberg, Jeffrey C; Kimberly, Robert P; Zhang, Jie; Langefeld, Carl D; Vilá, Luis M; Reveille, John D

2008-09-15

To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality.

Features Associated With, and the Impact of, Hemolytic Anemia in Patients With Systemic Lupus Erythematosus: LX, Results From a Multiethnic Cohort

PubMed Central

DURÁN, SERGIO; APTE, MANDAR; ALARCÓN, GRACIELA S.; MARION, MIRANDA C.; EDBERG, JEFFREY C.; KIMBERLY, ROBERT P.; ZHANG, JIE; LANGEFELD, CARL D.; VILÁ, LUIS M.; REVEILLE, JOHN D.

2009-01-01

Objective To examine the clinical and genetic correlates of hemolytic anemia and its impact on damage accrual and mortality in systemic lupus erythematosus (SLE) patients. Methods SLE patients (American College of Rheumatology [ACR] criteria) of Hispanic (Texan or Puerto Rican), African American, and Caucasian ethnicity from the LUMINA (LUpus in MInorities, NAture versus nurture) cohort were studied. Hemolytic anemia was defined as anemia with reticulocytosis (ACR criterion). The association between degrees of hemolytic anemia and socioeconomic/demographic, clinical, pharmacologic, immunologic, psychological, and behavioral variables was examined by univariable and multivariable (proportional odds model) analyses. Genetic variables (FCGR and Fas/Fas ligand polymorphisms) were examined by 2 degrees of freedom test of association and Cochran-Armitage trend tests. The impact of hemolytic anemia on damage accrual and mortality was examined by multivariable linear and Cox regression analyses, respectively. Results Of 628 patients studied, 90% were women, 19% were Texan Hispanic, 16% were Puerto Rican Hispanic, 37% were African American, and 28% were Caucasian. Sixty-five (10%) patients developed hemolytic anemia at some time during the disease course, 83% at or before diagnosis. Variables independently associated with degrees of hemolytic anemia were African American ethnicity, thrombocytopenia, and the use of azathioprine. Hemolytic anemia was associated with damage accrual after adjusting for variables known to affect this outcome; however, hemolytic anemia was not associated with mortality. Conclusion The association of hemolytic anemia with thrombocytopenia suggests a common mechanism in their pathophysiology. Hemolytic anemia is an early disease manifestation and is associated with African American ethnicity and the use of azathioprine; it appears to exert an impact on damage but not on mortality. PMID:18759263

Evaluation of the TREX1 gene in a large multi-ancestral lupus cohort

PubMed Central

Namjou, Bahram; Kothari, Parul H.; Kelly, Jennifer A.; Glenn, Stuart B.; Ojwang, Joshua O.; Adler, Adam; Alarcón-Riquelme, Marta E.; Gallant, Caroline J.; Boackle, Susan A.; Criswell, Lindsey A.; Kimberly, Robert P.; Brown, Elizabeth; Edberg, Jeffrey; Stevens, Anne M.; Jacob, Chaim O.; Tsao, Betty P.; Gilkeson, Gary S.; Kamen, Diane L.; Merrill, Joan T.; Petri, Michelle; Goldman, Rosalind Ramsey; Vila, Luis M.; Anaya, Juan-Manuel; Niewold, Timothy B.; Martin, Javier; Pons-Estel, Bernardo A.; Sabio, Jose M.; Callejas, Jose L.; Vyse, Timothy J.; Bae, Sang-Cheol; Perrino, Fred W.; Freedman, Barry I.; Scofield, R. Hal; Moser, Kathy L.; Gaffney, Patrick M.; James, Judith A.; Langefeld, Carl D.; Kaufman, Kenneth M.; Harley, John B.; Atkinson, John P.

2011-01-01

Systemic Lupus Erythematosus (SLE) is a prototypic autoimmune disorder with a complex pathogenesis in which genetic, hormonal and environmental factors play a role. Rare mutations in the TREX1 gene, the major mammalian 3′-5′ exonuclease, have been reported in sporadic SLE cases. Some of these mutations have also been identified in a rare pediatric neurologic condition featuring an inflammatory encephalopathy known as Aicardi-Goutières syndrome (AGS). We sought to investigate the frequency of these mutations in a large multi-ancestral cohort of SLE cases and controls. Methods Forty single-nucleotide polymorphisms (SNPs), including both common and rare variants, across the TREX1 gene were evaluated in ∼8370 patients with SLE and ∼7490 control subjects. Stringent quality control procedures were applied and principal components and admixture proportions were calculated to identify outliers for removal from analysis. Population-based case-control association analyses were performed. P values, false discovery rate q values, and odds ratios with 95% confidence intervals were calculated. Results The estimated frequency of TREX1 mutations in our lupus cohort was 0.5%. Five heterozygous mutations were detected at the Y305C polymorphism in European lupus cases but none were observed in European controls. Five African cases incurred heterozygous mutations at the E266G polymorphism and, again, none were observed in the African controls. A rare homozygous R114H mutation was identified in one Asian SLE patient whereas all genotypes at this mutation in previous reports for SLE were heterozygous. Analysis of common TREX1 SNPs (MAF >10%) revealed a relatively common risk haplotype in European SLE patients with neurologic manifestations, especially seizures, with a frequency of 58% in lupus cases compared to 45% in normal controls (p=0.0008, OR=1.73, 95% CI=1.25-2.39). Finally, the presence or absence of specific autoantibodies in certain populations produced significant

Long-term survival of kidney grafts in lupus nephritis: a Mexican cohort.

PubMed

Ramirez-Sandoval, J C; Chavez-Chavez, H; Wagner, M; Vega-Vega, O; Morales-Buenrostro, L E; Correa-Rotter, R

2018-07-01

Kidney transplant for patients with lupus nephritis (LN) has satisfactory outcomes in studies with short-term or mid-term follow up. Nevertheless, information about long-term outcomes is scarce. We performed a retrospective matched-pair cohort study in 74 LN recipients compared with 148 non-LN controls matched by age, sex, immunosuppressive treatment, human leukocyte antigen (HLA) matches, and transplant period in order to evaluate long-term outcomes of kidney transplant in LN recipients. Matched pairs were predominantly females (83%), median age at transplant surgery of 32 years (interquartile range 23-38 years), and 66% received a graft from a living related donor. Among LN recipients, 5-, 10-, 15-, and 20-year graft survival was 81%, 79%, 57% and 51%, respectively, and it was similar to that observed in controls (89%, 78%, 64%, and 56%, respectively). Graft loss (27% vs. 21%, p = 0.24) and overall survival ( p = 0.15) were not different between LN recipients and controls. Also, there was no difference in episodes of immunological rejection, thrombosis, or infection. Only six LN recipients had biopsy-proven lupus recurrence and three of them had graft loss. In a cohort with a long follow up of kidney transplant recipients, LN recipients had similar long-term graft survival and overall outcomes compared with non-lupus recipients when predictors are matched between groups.

Coffee Intake and Risk of Type 2 Diabetes: The Multiethnic Cohort

PubMed Central

Doo, Taisha; Morimoto, Yukiko; Steinbrecher, Astrid; Kolonel, Laurence N.; Maskarinec, Gertraud

2014-01-01

Objective We evaluated the influence of coffee consumption on diabetes incidence among the Hawaii component of the Multiethnic Cohort (MEC). Design Prospective cohort. Setting Population-based sample residing in Hawaii. Subjects After exclusions, 75,140 men and women of Caucasian, Japanese American, and Native Hawaiian ancestry aged 45–75 were part of this analysis. All participants provided information on diet and lifestyle through a food frequency questionnaire. After 14 years of follow-up 8,582 incident diabetes cases were identified using self-reports, medication questionnaires, and health plan linkages. Hazard ratios (HR) and 95% confidence intervals (95%CI) were calculated using Cox regression while adjusting for known covariates. Results The risk for diabetes associated with total coffee consumption differed by sex (Pinteraction<0.0001). Women consuming ≥3 cups/day of any type of coffee had a significantly lower risk (HR: 0.66; 95%CI: 0.58, 0.77; Ptrend<0.0001) than those reporting <1 cup, whereas the relation in men was borderline (HR: 0.89; 95%CI: 0.80, 0.99; Ptrend=0.09). The same difference by sex was seen for regular coffee with HRs of 0.65 (95%CI: 0.54, 0.78; Ptrend<0.0001) and 0.86 (95%CI: 0.75, 0.98; Ptrend=0.09) in men and women, respectively. No significant association with diabetes was apparent for decaffeinated coffee in women (HR: 0.85; 95%CI: 0.72, 1.01; Ptrend=0.73) or men (HR: 1.07; 95%CI: 0.93, 1.23; Ptrend=0.71). Despite small differences by ethnicity, the interaction terms between coffee intake and ethnicity were not significant. Conclusions In this multiethnic population, regular, but not decaffeinated, coffee intake was much more protective against diabetes in women of all ethnic groups than in men. PMID:23442347

Plasma carotenoids, retinol, and tocopherols and postmenopausal breast cancer risk in the Multiethnic Cohort Study: a nested case-control study

PubMed Central

Epplein, Meira; Shvetsov, Yurii B; Wilkens, Lynne R; Franke, Adrian A; Cooney, Robert V; Le Marchand, Loïc; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2009-01-01

Introduction Assessments by the handful of prospective studies of the association of serum antioxidants and breast cancer risk have yielded inconsistent results. This multiethnic nested case-control study sought to examine the association of plasma carotenoids, retinol, and tocopherols with postmenopausal breast cancer risk. Methods From the biospecimen subcohort of the Multiethnic Cohort Study, 286 incident postmenopausal breast cancer cases were matched to 535 controls on age, sex, ethnicity, study location (Hawaii or California), smoking status, date/time of collection and hours of fasting. We measured prediagnostic circulating levels of individual carotenoids, retinol, and tocopherols. Conditional logistic regression was used to compute odds ratios and 95% confidence intervals. Results Women with breast cancer tended to have lower levels of plasma carotenoids and tocopherols than matched controls, but the differences were not large or statistically significant and the trends were not monotonic. No association was seen with retinol. A sensitivity analysis excluding cases diagnosed within 1 year after blood draw did not alter the findings. Conclusions The lack of significant associations in this multiethnic population is consistent with previously observed results from less racially-diverse cohorts and serves as further evidence against a causal link between plasma micronutrient concentrations and postmenopausal breast cancer risk. PMID:19619335

Angiotensin-converting enzyme inhibitors delay the occurrence of renal involvement and are associated with a decreased risk of disease activity in patients with systemic lupus erythematosus--results from LUMINA (LIX): a multiethnic US cohort.

PubMed

Durán-Barragán, S; McGwin, G; Vilá, L M; Reveille, J D; Alarcón, G S

2008-07-01

To examine if angiotensin-converting enzyme (ACE) inhibitor use delays the occurrence of renal involvement and decreases the risk of disease activity in SLE patients. SLE patients (Hispanics, African Americans and Caucasians) from the lupus in minorities: nature vs nurture (LUMINA) cohort were studied. Renal involvement was defined as ACR criterion and/or biopsy-proven lupus nephritis. Time-to-renal involvement was examined by univariable and multivariable Cox proportional hazards regression analyses. Disease activity was examined with a case-crossover design and a conditional logistic regression model; in the case intervals, a decrease in the SLAM-R score >or=4 points occurred but not in the control intervals. Eighty of 378 patients (21%) were ACE inhibitor users; 298 (79%) were not. The probability of renal involvement free-survival at 10 yrs was 88.1% for users and 75.4% for non-users (P = 0.0099, log rank test). Users developed persistent proteinuria and/or biopsy-proven lupus nephritis (7.1%) less frequently than non-users (22.9%), P = 0.016. By multivariable Cox proportional hazards regression analyses, ACE inhibitors use [hazard ratio (HR) 0.27; 95% CI 0.09, 0.78] was associated with a longer time-to-renal involvement occurrence whereas African American ethnicity (HR 3.31; 95% CI 1.44, 7.61) was with a shorter time. ACE inhibitor use (54/288 case and 254/1148 control intervals) was also associated with a decreased risk of disease activity (HR 0.56; 95% CI 0.34, 0.94). ACE inhibitor use delays the development of renal involvement and associates with a decreased risk of disease activity in SLE; corroboration of these findings in other lupus cohorts is desirable before practice recommendations are formulated.

Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort.

PubMed

Setiawan, Veronica Wendy; Pandol, Stephen J; Porcel, Jacqueline; Wei, Pengxiao C; Wilkens, Lynne R; Le Marchand, Loïc; Pike, Malcolm C; Monroe, Kristine R

2017-02-01

Pancreatitis is a source of substantial morbidity and health cost in the United States. Little is known about how diet might contribute to its pathogenesis. To characterize dietary factors that are associated with risk of pancreatitis by disease subtype, we conducted a prospective analysis of 145,886 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. In the Multiethnic Cohort (age at baseline, 45-75 y), we identified cases of pancreatitis using hospitalization claim files from 1993 through 2012. Patients were categorized as having gallstone-related acute pancreatitis (AP) (n = 1210), AP not related to gallstones (n = 1222), or recurrent AP or suspected chronic pancreatitis (n = 378). Diet information was obtained from a questionnaire administered when the study began. Associations were estimated by hazard ratios and 95% confidence intervals using Cox proportional hazard models adjusted for confounders. Dietary intakes of saturated fat (P trend = .0011) and cholesterol (P trend = .0008) and their food sources, including red meat (P trend < .0001) and eggs (P trend = .0052), were associated positively with gallstone-related AP. Fiber intake, however, was associated inversely with gallstone-related AP (P trend = .0005) and AP not related to gallstones (P trend = .0035). Vitamin D, mainly from milk, was associated inversely with gallstone-related AP (P trend = .0015), whereas coffee consumption protected against AP not related to gallstones (P trend < .0001). With the exception of red meat, no other dietary factors were associated with recurrent acute or suspected chronic pancreatitis. Associations between dietary factors and pancreatitis were observed mainly for gallstone-related AP. Interestingly, dietary fiber protected against AP related and unrelated to gallstones. Coffee drinking protected against AP not associated with gallstones. Further studies are warranted to confirm our findings. Copyright �

Renal Interstitial Arteriosclerotic Lesions in Lupus Nephritis Patients: A Cohort Study from China

PubMed Central

Qin, Dan-dan; Wu, Li-hua; Song, Yan; Yu, Feng; Wang, Su-xia; Liu, Gang; Zhao, Ming-hui

2015-01-01

Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their associations with clinical and pathological characteristics, especially cardio-vascular features. Design A retrospective cohort study. Participants Seventy-nine patients with renal biopsy-proven lupus nephritis, diagnosed between January 2000 and June 2008 from Peking University First Hospital. Results In clinico-pathological data, patients with arteriosclerosis had higher ratio of hypertension and more severe renal injury indices compared with patients with no renal vascular lesions. More importantly, patients with renal arteriosclerosis had worse cardiac structure and function under transthoracic echocardiographic examination. Patients with renal arteriosclerosis tend to have higher ratios of combined endpoints compared with those of no renal vascular lesions, although the difference didn’t reach statistical meanings (P = 0.104). Conclusion Renal arteriosclerotic lesion was common and associated with vascular immune complex deposits in lupus nephritis. It might have a certain degree of association with poor outcomes and cardiovascular events, which needs further explorations. PMID:26544865

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA L II): relationship between vascular events and the use of hormone replacement therapy in postmenopausal women.

PubMed

Fernández, Mónica; Calvo-Alén, Jaime; Bertoli, Ana M; Bastian, Holly M; Fessler, Barri J; McGwin, Gerald; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

2007-10-01

To examine the influence of hormone replacement therapy (HRT) in the occurrence of vascular arterial and venous thrombotic events in postmenopausal women with systemic lupus erythematosus (SLE). SLE women aged > or =16 years, disease duration < or =5 years from LUMINA, a multiethnic, longitudinal outcome study, were included. Menopause was defined at disease onset as the presence of amenorrhea >6 months and/or oophorectomy, and/or increased follicle stimulating hormone values, and/or HRT use regardless of the presence or absence of climacteric symptoms (hot flashes). Patients were divided into HRT ever users and nonusers. Patients with positive antiphospholipid antibodies (n = 9) or vascular arterial events (n = 1) occurring before HRT use were excluded. The occurrence of vascular arterial and venous thrombotic events was compared between HRT users and HRT nonusers and its role examined by logistic regression after adjusting for "confounding by indication" using propensity score or logistic regression analyses. Seventy-two postmenopausal women, 32 (44%) HRT users and 40 (56%) HRT nonusers, were studied. HRT use was associated with fewer vascular arterial but not venous thrombotic events (P = 0.021) in the univariable analyses. However, after adjusting for the propensity score, HRT use was no longer significant (P = 0.064). Comparable results were obtained by logistic regression. HRT use was not associated with the occurrence of vascular arterial events in the LUMINA patients. HRT use in women with SLE should be individualized, but our data suggest its use may be safe if antiphospholipid antibodies are not present or vascular arterial events have not previously occurred.

Chronic kidney disease, cardiovascular disease and mortality: A prospective cohort study in a multi-ethnic Asian population.

PubMed

Lim, Cynthia C; Teo, Boon Wee; Ong, Peng Guan; Cheung, Carol Y; Lim, Su Chi; Chow, Khuan Yew; Meng, Chan Choon; Lee, Jeannette; Tai, E Shyong; Wong, Tien Y; Sabanayagam, Charumathi

2015-08-01

Few studies have examined the impact of chronic kidney disease (CKD) on adverse cardiovascular outcomes and deaths in Asian populations. We evaluated the associations of CKD with cardiovascular disease (CVD) and all-cause mortality in a multi-ethnic Asian population. Prospective cohort study of 7098 individuals who participated in two independent population-based studies involving Malay adults (n = 3148) and a multi-ethnic cohort of Chinese, Malay and Indian adults (n = 3950). CKD was assessed from CKD-EPI estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR). Incident CVD (myocardial infarction, stroke and CVD mortality) and all-cause mortality were identified by linkage with national disease/death registries. Over a median follow-up of 4.3 years, 4.6% developed CVD and 6.1% died. Risks of both CVD and all-cause mortality increased with decreasing eGFR and increasing albuminuria (all p-trend <0.05). Adjusted hazard ratios (HR (95% confidence interval)) of CVD and all-cause mortality were: 1.54 (1.05-2.27) and 2.21 (1.67-2.92) comparing eGFR <45 vs ≥60; 2.81 (1.49-5.29) and 2.34 (1.28-4.28) comparing UACR ≥300 vs <30. The association between eGFR <60 and all-cause mortality was stronger among those with diabetes (p-interaction = 0.02). PAR of incident CVD was greater among those with UACR ≥300 (12.9%) and that of all-cause mortality greater among those with eGFR <45 (16.5%). In multi-ethnic Asian adults, lower eGFR and higher albuminuria were independently associated with incident CVD and all-cause mortality. These findings extend previously reported similar associations in Western populations to Asians and emphasize the need for early detection of CKD and intervention to prevent adverse outcomes. © The European Society of Cardiology 2014.

Factors associated with disease expression patterns in systemic lupus erythematosus patients: results from LUMINA (LXXVII), a multiethnic US cohort.

PubMed

Ugarte-Gil, M F; Pimentel-Quiroz, V R; Vilá, L M; Reveille, J D; McGwin, G; Alarcón, G S

2017-05-01

Objective The objective of this study was to determine the association of disease expression patterns with demographic and clinical characteristics in SLE. Methods Patients from a multi-ethnic SLE cohort were included. Disease expression patterns were defined as acute SLE and insidious SLE; this group was divided into those who accrued three ACR criteria and then accrued the fourth (insidious pattern A) and those who have one or two and then accrued four criteria (insidious pattern B). Disease activity was ascertained with the SLAM-R and disease damage with SLICC/ACR damage index. Variables were compared using analysis of variance for numeric variables and χ 2 for categorical variables. Multivariable analyses adjusting for possible confounders were performed. Results Six hundred and forty patients were included; the most frequent pattern was the insidious pattern B, with 415 (64.8%) patients, followed by the acute SLE group with 115 (18.0%) and the insidious pattern A with 110 (17.2%) patients. Patients from the insidious pattern A were older at diagnosis (pattern A: 39.8 vs pattern B: 36.7 vs acute: 32.4 years; p < 0.0001), more educated (13.6 vs 13.1 vs 12.1; p = 0.0008) and with a less active disease at baseline (8.8 vs 9.2 vs 10.7; p = 0.0227). Caucasian and Hispanic (Puerto Rico) ethnicities were overrepresented in this group (40.0% vs 27.7% vs 19.1% and 18.2% vs 17.1% vs 9.6%; p = 0.0003). Conclusions More insidious onset is associated with older age, Caucasian ethnicity, higher level of education, and lower disease activity than those with acute onset. However, after multivariable analyses, disease activity was not associated with any disease expression pattern.

Neuropsychiatric lupus: the prevalence and autoantibody associations depend on the definition: results from the 1000 faces of lupus cohort.

PubMed

Borowoy, Alan M; Pope, Janet E; Silverman, Earl; Fortin, Paul R; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Gladman, Dafna; Urowitz, Murray; Zummer, Michel; Hudson, Marie; Tucker, Lori; Peschken, Christine

2012-10-01

The (ever) prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) can vary widely depending on the definition used. We determined the prevalence of NPSLE in 1000 Faces of Lupus, a large multicenter Canadian cohort. Adults enrolled at 10 sites who satisfied the American College of Rheumatology (ACR) classification for systemic lupus erythematosus (SLE) were included. NPSLE was defined as (i) NPSLE by ACR classification criteria (seizures or psychosis), (ii) ACR, SLEDAI (seizure, psychosis, organic brain syndrome, cranial nerve disorder, headache, and cerebrovascular accident (CVA)), SLAM (CVA, seizure, cortical dysfunction, and headache), and SLICC (cognitive impairment, psychosis, seizures, CVA, cranial or peripheral neuropathy, and transverse myelitis) with and (iii) without minor nonspecific NPSLE manifestations (including mild depression, mild cognitive impairment, and electromyogram-negative neuropathies), and (iv) by ACR and SLEDAI neuropsychiatric (NP) indexes alone. Factors associated with NPSLE were explored using regression models. Cohort size was 1253, with mean disease 12 ± 10 years, mean age 41 ± 16 years, and 86% female. Subgroup size was dependent on the specific definition of NPSLE. Prevalence of NPSLE was 6.4% in group (i), n = 1253 (n = 80); 38.6% in group (ii), n = 681(n = 263); 28.7% in group (iii), n = 586 (n = 168); and 10.2% in group (iv), n = 1125 (n = 115). In univariate analysis, Aboriginals had a nearly 2-fold increase in frequency of NPSLE in all groups. Education level and income were not associated with NPSLE (P = 0.32 and 0.03, respectively). As well, number of ACR criteria, SLAM, age at diagnosis, disease duration, and gender were not associated with NPSLE. Anti-Ro was significantly associated in groups (i) and (iv) and antiphospholipid antibodies (aPL) were increased in groups (i), (ii), and (iii); however, this lost significance when thromboembolic events were excluded from SLICC, SLEDAI, and SLAM indexes. In group

Prevalence and associations of neuropathic pain in a cohort of multi-ethnic Asian low back pain patients.

PubMed

Kew, Yueting; Tan, Cheng-Yin; Ng, Chong-Jing; Thang, Sue-Sien; Tan, Leong-Hooi; Khoo, Yvonne Khaii; Lim, Jun-Ni; Ng, Jia-Hui; Chan, Chris Yin-Wei; Kwan, Mun-Keong; Goh, Khean-Jin

2017-04-01

The prevalence of neuropathic low back pain differs in different ethnic populations. The aims of the study are to determine its frequency and associations in a multi-ethnic cohort of Asian low back pain patients. This was a cross-sectional study of low back patients seen at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia. Neuropathic low back pain patients were identified using the painDETECT questionnaire and compared with non-neuropathic (unclear or nociceptive) low back pain patients, in terms of socio-demographic and clinical factors, pain severity (numerical pain rating scale, NPRS), disability (Roland Morris Disability Questionnaire, RMDQ), as well as anxiety and depression (Hospital Anxiety and Depression Scale, HADS). Of 210 patients, 26 (12.4%) have neuropathic low back pain. Neuropathic pain is associated with non-Chinese ethnicity, higher body mass index and pain radiation below the knee. Patients with neuropathic pain have significantly higher NPRS and RMDQ scores, and there are more subjects with anxiety on HADS. However, there are no differences between the groups in age, gender, pain duration or underlying diagnosis of low back pain. The prevalence of neuropathic low back pain in a multi-ethnic Malaysian cohort is lower than previously reported in other populations with possible differences between ethnic groups. It is associated with greater pain severity, disability and anxiety.

Steroid-induced diabetes mellitus in systemic lupus erythematosus patients: analysis from a Malaysian multi-ethnic lupus cohort.

PubMed

Shaharir, Syahrul Sazliyana; Gafor, Abdul Halim Abdul; Said, Mohd Shahrir Mohamed; Kong, Norella C T

2015-06-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease and glucocorticoid is the mainstay of treatment in SLE. The reported incidence of steroid-induced diabetes mellitus (SDM) ranged between 1-53%. We sought to investigate the prevalence and associated factors of SDM in patients with SLE. A total of 100 SLE patients attending the Nephrology/SLE and Rheumatology Clinic, Universiti Kebangsaan Malaysia Medical Centre (UKMMC) who received corticosteroid treatment were recruited. The diagnosis of diabetes mellitus was based on the 2010 American Diabetes Association's criteria. Prevalent cases of SDM were also included. Statistical analysis was performed to determine the factors associated with SDM. Thirteen of them (13%) developed SDM, with the median onset of diagnosis from commencement of glucocorticoid treatment being 8 years (range 0.5-21 years). Although only seven Indians were recruited into the study, three of them (42.9%) had SDM compared to Malays (9.3%) and Chinese (12.8%) (P ≤ 0.05). Univariate and multivariate analysis showed that higher numbers of system or organ involvement in SLE, abdominal obesity, hypertriglyceridemia and daily prednisolone of ≥ 1 mg/kg/day were the important associated factors of SDM (P ≤ 0.05). Meanwhile, hydroxychloroquine (HCQ) use was associated with reduced SDM prevalence (P < 0.05). The prevalence of SDM among SLE patients was 13% and Indians were more prone to develop SDM compared to other races. Higher numbers of system involvement, abdominal obesity, hypertriglyceridemia and the use of oral prednisolone of ≥ 1 mg/kg/day were associated with SDM, while HCQ use potentially protects against SDM. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Associated factors and impact of myocarditis in patients with SLE from LUMINA, a multiethnic US cohort (LV). [corrected].

PubMed

Apte, M; McGwin, G; Vilá, L M; Kaslow, R A; Alarcón, G S; Reveille, J D

2008-03-01

To examine the factors associated with myocarditis and its impact on disease outcomes in SLE patients. SLE patients aged > or = 16 yrs, disease duration < or = 5 yrs from LUMINA (LUpus in Minorities: NAture vs nurture), a multiethnic US cohort, were studied. Myocarditis was defined as per the category 3 of the pericarditis/myocarditis item of the SLAM-Revised (SLAM-R). Patients with concurrent pericardial involvement were excluded. Patients with myocarditis were compared with those without myocarditis or its sequelae in the preceding year. The association between myocarditis and baseline variables (T(0)) was first examined. The impact of myocarditis on disease activity over time (SLAM-R), damage accrual [SLICC Damage Index (SDI)] at last visit (T(L)) and mortality was evaluated. Fifty-three of the 496 patients studied had myocarditis. African American ethnicity [Odds ratio (OR) = 12.6; 95% CI 1.6, 97.8] and SLAM-R at diagnosis (OR = 1.1, 95% CI 1.0, 1.1) were significantly and independently associated with myocarditis. Myocarditis did not predict disease activity over time, but approached significance as a predictor of SDI at T(L) in multivariable analyses P = 0.051. Kaplan-Meier curves indicated that myocarditis was associated with shorter survival (log-rank = 4.87, P = 0.02), particularly in patients with > or = 5 yrs disease; however, myocarditis was not retained in the Cox proportional hazards regression model. Ethnicity and disease activity at diagnosis were associated with the occurrence of myocarditis in SLE. Myocarditis did not significantly impact on disease activity over time, but impacts some on damage accrual and survival, reflecting overall the more severe disease those patients experience.

Anti-pentraxin 3 auto-antibodies might be protective in lupus nephritis: a large cohort study.

PubMed

Yuan, Mo; Tan, Ying; Pang, Yun; Li, Yong-Zhe; Song, Yan; Yu, Feng; Zhao, Ming-Hui

2017-11-01

Anti-pentraxin 3 (PTX3) auto-antibodies were found to be associated with the absence of renal involvement in systemic lupus erythematosus (SLE). This study is to investigate the prevalence of anti-PTX3 auto-antibodies and their clinical significance based on a large Chinese lupus nephritis cohort. One hundred and ninety-six active lupus nephritis patients, 150 SLE patients without clinical renal involvement, and 100 healthy controls were enrolled. Serum anti-PTX3 auto-antibodies and PTX3 levels were screened by enzyme-linked immunosorbent assay (ELISA). The associations between anti-PTX3 auto-antibodies and clinicopathological parameters in lupus nephritis were further analyzed. Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement (19.4% (38/196) versus 40.7% (61/150), p < .001). The serum levels of anti-PTX3 auto-antibodies were negatively correlated with proteinuria in lupus nephritis (r = -.143, p = .047). The levels of proteinuria, serum creatinine, and the prevalence of thrombotic microangiopathy were significantly higher in patients with higher PTX3 levels (≥3.207 ng/ml) and without anti-PTX3 auto-antibodies compared with patients with lower PTX3 levels (<3.207 ng/ml) and with anti-PTX3 auto-antibodies (4.79 (3.39-8.28) versus 3.95 (1.78-7.0), p = .03; 168.84 ± 153.63 versus 101.44 ± 47.36, p = .01; 34.1% (14/41) versus 0% (0/9), p = .04; respectively). Anti-PTX3 auto-antibodies were less prevalent in active lupus nephritis patients compared with SLE without renal involvement and associated with less severe renal damage, especially with the combined evaluation of serum PTX3 levels.

Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort.

PubMed

Urowitz, M B; Gladman, D D; Ibañez, D; Fortin, P R; Bae, S C; Gordon, C; Clarke, A; Bernatsky, S; Hanly, J G; Isenberg, D; Rahman, A; Sanchez-Guerrero, J; Wallace, D J; Ginzler, E; Alarcón, G S; Merrill, J T; Bruce, I N; Sturfelt, G; Nived, O; Steinsson, K; Khamashta, M; Petri, M; Manzi, S; Ramsey-Goldman, R; Dooley, M A; van Vollenhoven, R F; Ramos, M; Stoll, T; Zoma, A; Kalunian, K; Aranow, C

2012-01-01

We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort. The Systemic Lupus International Collaborating Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI over time between whites and nonwhites. Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as "other." At enrollment, the mean age was 35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained low. SLEDAI-2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti-DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not. Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period. Copyright © 2012 by the American College of Rheumatology.

Adverse pregnancy outcomes in women with systemic lupus erythematosus from a multiethnic US cohort: LUMINA (LVI) [corrected].

PubMed

Andrade, R; Sanchez, M L; Alarcón, G S; Fessler, B J; Fernández, M; Bertoli, A M; Apte, M; Vilá, L M; Arango, A M; Reveille, J D

2008-01-01

To study the factors associated with an adverse pregnancy outcome in women with systemic lupus erythematosus (SLE). SLE women from LUMINA of Hispanic, African American and Caucasian ethnicity were studied. Adverse pregnancy outcome was a miscarriage or abortion (<20 weeks), a stillbirth (> or = 20) and/or a moderate to severe preterm-baby (<34 weeks); good outcome was either a mild preterm-baby (> or = 34 weeks) or a full-term baby [C-section or vaginal delivery (38-42 weeks)]. Pregnancies occurring after SLE diagnosis (TD) were included; pregnancy outcome was the unit of analyses. The relationship between selected variables and pregnancy outcomes was examined by univariable and multivariable analyses. Adverse outcomes occurred in 63.7% of 102 pregnancies. In the univariable analyses, Texan Hispanic and African American ethnicities, fewer years of education, higher number of ACR criteria, renal involvement, glucocorticoid exposure and the maximum dose of glucocorticoids used prior to the pregnancy outcome were associated with an adverse pregnancy outcome. Renal involvement was independently associated with an adverse pregnancy outcome [Odds ratio (OR)=5.219 (95% Confidence Interval (CI) 1.416-19.239, p=0.0131] as were the maximum dose of glucocorticoids used prior to the pregnancy outcome (OR=1.028; CI:1.002-1.054; p=0.0315) and fewer years of education (OR=1.204; CI:1.006-1.472; p=0.0437). Ethnicity was not retained in the multivariable model. Renal involvement, the maximum dose of glucocorticoids used prior to pregnancy and fewer years of education were associated with adverse pregnancy outcomes. These data have implications for the management of women with lupus planning to become pregnant.

Meat consumption and risk of type 2 diabetes: the Multiethnic Cohort.

PubMed

Steinbrecher, A; Erber, E; Grandinetti, A; Kolonel, L N; Maskarinec, G

2011-04-01

To examine the association of meat consumption with diabetes risk in the Hawaii component of the Multiethnic Cohort and to assess effect modification by ethnicity. A prospective cohort study. Baseline information on diet and lifestyle was assessed by questionnaire. The cohort was followed up for incident cases of diabetes, which were identified through self-reports, medication questionnaires, or health plan linkages. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for diabetes associated with quintile of meat consumption. Hawaii, USA. A total of 29,759 Caucasian, 35,244 Japanese-American and 10,509 Native Hawaiian men and women, aged 45-75 years at baseline. During a mean follow-up time of 14 years, 8587 incident diabetes cases were identified. Intake of red meat was positively associated with diabetes risk in men (fifth v. first quintile: HR=1.43; 95% CI 1.29, 1.59) and women (fifth v. first quintile: HR=1.30; 95% CI 1.17, 1.45) in adjusted models. The respective HR for processed red meat intake were 1.57 (95% CI 1.42, 1.75) and 1.45 (95% CI 1.30, 1.62). The association for processed poultry was weaker than for processed red meat, and fresh poultry intake was not associated with diabetes risk. For men only, we observed significant interactions of ethnicity with the red and processed red meat associations, with Caucasians experiencing slightly higher risks than Japanese-Americans. Our findings support the growing evidence that red and processed meat intake increase risk for diabetes irrespective of ethnicity and level of BMI.

Prognostic implications of active discoid lupus erythematosus and malar rash at the time of diagnosis of systemic lupus erythematosus: Results from a prospective cohort study.

PubMed

Drucker, A M; Su, J; Mussani, F; Siddha, S K; Gladman, D D; Urowitz, M B

2016-04-01

Cutaneous lupus erythematosus (CLE) may have prognostic implications for systemic lupus erythematosus (SLE). We aimed to determine the impact of discoid lupus erythematosus (DLE) and malar rash on SLE disease activity. Data were analyzed from the Toronto Lupus Clinic prospective cohort study. We compared SLE patients with active DLE or malar rash at SLE diagnosis to SLE patients who never developed CLE. Outcomes were assessed at one and five years, including Adjusted Mean Systemic Lupus Erythematosus Disease Activity Index 2000 (AMS). A total of 524 SLE patients (284 without CLE, 65 with DLE, and 175 with malar rash) were included. Mean AMS scores in patients without CLE at one and five years were 5.96 ± 5.06 and 4.00 ± 3.52, which did not differ significantly from scores at one (6.93 ± 5.31, p = 0.17) and five years (4.29 ± 2.62, p = 0.63) in the DLE group. In patients with malar rash, AMS scores at one (8.30 ± 6.80, p < 0.001) and five years (5.23 ± 3.06, p = 0.004) were higher than controls without CLE. Malar rash may be a marker of more severe systemic disease over time, while DLE has no significant impact on general SLE disease activity. © The Author(s) 2015.

Disease activity and transition outcomes in a childhood-onset systemic lupus erythematosus cohort.

PubMed

Son, M B; Sergeyenko, Y; Guan, H; Costenbader, K H

2016-11-01

Objective The chronicity and severity of childhood-onset systemic lupus erythematosus (cSLE) necessitate effective transition from pediatric to adult providers. We studied transition outcomes in a cSLE cohort. Methods We identified patients at an adult lupus clinic diagnosed with SLE ≤ 18 years who had been followed by a pediatric rheumatologist. Data extracted from the first three years in adult care ("post-transition period") included: sociodemographics, depression, anxiety, SLE manifestations, SLE Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/ACR Damage Index for SLE (SLICC) scores, non-adherence, and gaps in care (no appointments in the recommended time frame). Multivariable logistic regression analyses for predictors of: (1) time between pediatric and adult providers, (2) gaps in care, (3) unscheduled utilization (emergency department visits and admissions) (4) depression and/or anxiety were performed, as was a multivariable Poisson regression analysis for number of missed appointments. Results In 50 patients, SLEDAI scores were stable (mean 5.7 ± 5.0 at start vs. 4.7 ± 4.8 at year 3, p = 0.2), but SLICC scores increased (0.46 ± 0.84, vs. 0.78 ± 1.25, p = 0.01). Depression and anxiety increased significantly (10% vs. 26%, p = 0.02). Mean time from last pediatric to first adult provider visit was almost nine months (253 ± 392 days). Nearly 75% of patients had ≥ 1 gap in care. White race, low education level and non-adherence were significantly associated with missed appointments. Conclusion Despite moderate disease activity in this cSLE transition cohort, prolonged time between pediatric and adult providers and gaps in care in the post-transition period occurred. Anxiety and depression were frequently reported. Future work should identify methods to improve transition.

Energy Cost of Standing in a Multi-Ethnic Cohort: Are Energy-Savers a Minority or the Majority?

PubMed Central

Monnard, Cathríona R.

2017-01-01

Background The disease risks associated with sedentary behavior are now firmly established, and consequently there is much interest in methods of increasing low-intensity physical activity. In this context, it is a widely held belief that altering posture allocation can modify energy expenditure (EE) to impact upon body weight regulation and health. However, we recently showed the existence of two distinct phenotypes pertaining to the energy cost of standing–with the majority of a Caucasian cohort showing no sustained increase in EE during standing relative to sitting. Here we investigated whether this phenomenon is also observed across a multi-ethnic male cohort. Objective To determine the magnitude and time-course of changes in EE and respiratory quotient (RQ) during steady-state standing versus sitting, and to explore inter-individual variability in these responses across 4 ethnic groups (European, Indian, Chinese, African) Design Min-by-min monitoring using posture-adapted ventilated-hood indirect calorimetry was conducted in 35 healthy, men (20–43 years) during 10 min of steady-state standing versus sitting comfortably. Results 69% of subjects showed little or no increase (<5%) in EE during standing compared to sitting (energy savers). Furthermore, the proportion of energy savers did not significantly differ between ethnic groups, despite ethnic differences in anthropometry; with body weight as the primary predictor of the energy cost of standing maintenance (r2 = 0.30, p = 0.001). Conclusion Our results indicate that the majority of individuals in a multi-ethnic cohort display a postural energy-saver phenotype. The mechanisms by which the large majority of individuals appear to maintain sitting and standing postures at the same energetic cost remains to be elucidated but is of considerable importance to our understanding of the spontaneous physical activity compartment of EE and its potential as a target for weight regulation. PMID:28056094

X-linked Charcot-Marie-Tooth disease predominates in a cohort of multiethnic Malaysian patients.

PubMed

Shahrizaila, Nortina; Samulong, Sarimah; Tey, Shelisa; Suan, Liaw Chiew; Meng, Lao Kah; Goh, Khean Jin; Ahmad-Annuar, Azlina

2014-02-01

Data regarding Charcot-Marie-Tooth disease is lacking in Southeast Asian populations. We investigated the frequency of the common genetic mutations in a multiethnic Malaysian cohort. Patients with features of Charcot-Marie-Tooth disease or hereditary liability to pressure palsies were investigated for PMP22 duplication, deletion, and point mutations and GJB1, MPZ, and MFN2 point mutations. Over a period of 3 years, we identified 25 index patients. A genetic diagnosis was reached in 60%. The most common were point mutations in GJB1, accounting for X-linked Charcot-Marie-Tooth disease (24% of the total patient population), followed by PMP22 duplication causing Charcot-Marie-Tooth disease type 1A (20%). We also discovered 2 novel GJB1 mutations, c.521C>T (Proline174Leucine) and c.220G>A (Valine74Methionine). X-linked Charcot-Marie-Tooth disease was found to predominate in our patient cohort. We also found a better phenotype/genotype correlation when applying a more recently recommended genetic approach to Charcot-Marie-Tooth disease. Copyright © 2013 Wiley Periodicals, Inc.

Differences in musculoskeletal health due to gender in a rural multiethnic cohort: a Project FRONTIER study.

PubMed

Brismée, J M; Yang, S; Lambert, M E; Chyu, M C; Tsai, P; Zhang, Y; Han, J; Hudson, C; Chung, Eunhee; Shen, C L

2016-04-26

Very few studies have investigated differences in musculoskeletal health due to gender in a large rural population. The aim of this study is to investigate factors affecting musculoskeletal health in terms of hand grip strength, musculoskeletal discomfort, and gait disturbance in a rural-dwelling, multi-ethnic cohort. Data for 1117 participants (40 years and older, 70% female) of an ongoing rural healthcare study, Project FRONTIER, were analyzed. Subjects with a history of neurological disease, stroke and movement disorder were excluded. Dominant hand grip strength was assessed by dynamometry. Gait disturbance including stiff, spastic, narrow-based, wide-based, unstable or shuffling gait was rated. Musculoskeletal discomfort was assessed by self-reported survey. Data were analyzed by linear, logistic regression and negative binomial regressions as appropriate. Demographic and socioeconomic factors were adjusted in the multiple variable analyses. In both genders, advanced age was a risk factor for weaker hand grip strength; arthritis was positively associated with musculoskeletal discomfort, and fair or poor health was significantly associated with increased risk of gait disturbance. Greater waist circumference was associated with greater musculoskeletal discomfort in males only. In females, advanced age is the risk factor for musculoskeletal discomfort as well as gait disturbance. Females with fair or poor health had weaker hand grip strength. Higher C-reactive protein and HbA1c levels were also positively associated with gait disturbance in females, but not in males. This cross-sectional study demonstrates how gender affects hand grip strength, musculoskeletal discomfort, and gait in a rural-dwelling multi-ethnic cohort. Our results suggest that musculoskeletal health may need to be assessed differently between males and females.

Features associated with hematologic abnormalities and their impact in patients with systemic lupus erythematosus: Data from a multiethnic Latin American cohort.

PubMed

González-Naranjo, Luis A; Betancur, Octavio Martínez; Alarcón, Graciela S; Ugarte-Gil, Manuel F; Jaramillo-Arroyave, Daniel; Wojdyla, Daniel; Pons-Estel, Guillermo J; Rondón-Herrera, Federico; Vásquez-Duque, Gloria M; Quintana-López, Gerardo; Da Silva, Nilzio A; Tavares Brenol, João C; Reyes-Llerena, Gil; Pascual-Ramos, Virginia; Amigo, Mary C; Massardo, Loreto; Alfaro-Lozano, José; Segami, María I; Esteva-Spinetti, María H; Iglesias-Gamarra, Antonio; Pons-Estel, Bernardo A

2016-06-01

To examine hematological manifestations' correlates and their impact on damage accrual and mortality in SLE patients from the multiethnic, Latin American, GLADEL cohort. In patients with recent SLE diagnosis (≤2 years), the association between follow-up hematological manifestations (per ACR criteria) and socio-demographic and clinical variables was examined by univariable and multivariable logistic regressions; their impact on damage accrual and mortality was examined by Poisson and Cox proportional-hazards regression analyses, respectively. Of 1437 patients, 948 (66.0%) developed ≥1 hematological manifestation [5.5% hemolytic anemia (AHA), 16.3% thrombocytopenia, and 56.4% lymphopenia] over 4.3 (3.3) follow-up years. Younger age, Mestizo ethnicity, hematologic disorder (at/or before SLE diagnosis), and first damage recorded were associated with hematological manifestations while antimalarials were negatively associated. AHA (at/or before SLE diagnosis), anti-Sm, and anti-RNP antibodies were associated with subsequent AHA occurrence while musculoskeletal involvement was negatively associated. Thrombocytopenia (at/or before SLE diagnosis), AHA, anti-phospholipid antibodies (aPLs), anti-SSA/Ro, anti-SSB/La antibodies, and first damage recorded were associated with later thrombocytopenia occurrence. Lymphopenia (at/or before SLE diagnosis), younger age at diagnosis, Mestizo ethnicity, having medical insurance, and first damage recorded were associated with subsequent lymphopenia occurrence while antimalarials and azathioprine treatment were negatively associated. AHA was associated with damage accrual and mortality after adjusting for variables known to affect these outcomes. Mestizo ethnicity and early hematological manifestations are risk factors for their subsequent occurrence while antimalarials have a protective effect. The associations between AHA and aPLs and thrombocytopenia were corroborated. AHA contributes independently to damage accrual and diminished

Prognostic value of metabolic syndrome for the development of cardiovascular disease in a cohort of premenopausal women with systemic lupus erythematosus.

PubMed

García-Villegas, Elsy Aidé; Lerman-Garber, Israel; Flores-Suárez, Luis Felipe; Aguilar-Salinas, Carlos; Márquez González, Horacio; Villa-Romero, Antonio Rafael

2015-04-08

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease of unknown etiology. In lupus patients there is an increased cardiovascular risk due to an accelerated atherogenesis. Furthermore, Metabolic Syndrome (MS) adds an independent risk for developing Cardiovascular Disease (CVD) in the population. Therefore, it is important to determine whether lupus patients have an increased risk of developing Cardiovascular Disease in the presence of MS. To estimate the prognostic value of MS in the incidence of cardiovascular events in a cohort of premenopausal patients with SLE. Cohort study in 238 patients was carried out. Clinical, biochemical, dietetic and anthropometric evaluations were performed. Patients were classified according to the prevalence of MS in 2001. There was a patient follow-up from 2001 to 2008. In 2008, after studying the records, we obtained the "cases" (patients with CVD) and the "no cases" (patients without CVD). The basal prevalence of MS in the cohort was of 21.8% (ATPIII). The MS component with the highest prevalence in the population studied in 2001 was low HDL-Cholesterol (<50mg/dL) with a prevalence of 55.0%. The cumulative incidence of CVD in the group with MS was 17.3% and in the group without MS it was 7.0% with a Relative Risk (RR) of 2.48 (1.12-5.46) and p<0.05. In the multivariable analysis it was noted that MS is a predictive factor of CVD. We observed the prognostic value of MS for an increased risk of cardiovascular damage in premenopausal patients with lupus. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

Association of coffee intake with reduced incidence of liver cancer and death from chronic liver disease in the US multiethnic cohort.

PubMed

Setiawan, Veronica Wendy; Wilkens, Lynne R; Lu, Shelly C; Hernandez, Brenda Y; Le Marchand, Loïc; Henderson, Brian E

2015-01-01

Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC) and chronic liver disease (CLD), but few data are available from prospective, US multiethnic populations. We evaluated the association of coffee intake with HCC and CLD in 162,022 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the US Multiethnic Cohort (MEC). We collected data from the MEC, a population-based prospective cohort study of >215,000 men and women from Hawaii and California, assembled in 1993-1996. Participants reported coffee consumption and other dietary and lifestyle factors when they joined the study. During an 18-year follow-up period, there were 451 incident cases of HCC and 654 deaths from CLD. Hazard rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using Cox regression, adjusting for known HCC risk factors. High levels of coffee consumption were associated with reduced risk of incident HCC and CLD mortality (Ptrend ≤ .0002). Compared with non-coffee drinkers, those who drank 2-3 cups per day had a 38% reduction in risk for HCC (RR = 0.62; 95% CI: 0.46-0.84); those who drank ≥4 cups per day had a 41% reduction in HCC risk (RR = 0.59; 95% CI: 0.35-0.99). Compared with non-coffee drinkers, participants who consumed 2-3 cups coffee per day had a 46% reduction in risk of death from CLD (RR = 0.54; 95% CI: 0.42-0.69) and those who drank ≥4 cups per day had a 71% reduction (RR = 0.29; 95% CI: 0.17-0.50). The inverse associations were similar regardless of the participants' ethnicity, sex, body mass index, smoking status, alcohol intake, or diabetes status. Increased coffee consumption reduces the risk of HCC and CLD in multiethnic US populations. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

High-Quality Diets Associate With Reduced Risk of Colorectal Cancer: Analyses of Diet Quality Indexes in the Multiethnic Cohort.

PubMed

Park, Song-Yi; Boushey, Carol J; Wilkens, Lynne R; Haiman, Christopher A; Le Marchand, Loïc

2017-08-01

Healthy eating patterns assessed by diet quality indexes (DQIs) have been related to lower risk of colorectal cancer-mostly among whites. We investigated the associations between 4 DQI scores (the Healthy Eating Index 2010 [HEI-2010], the Alternative Healthy Eating Index 2010 [AHEI-2010], the alternate Mediterranean diet score [aMED], and the Dietary Approaches to Stop Hypertension score) and colorectal cancer risk in the Multiethnic Cohort. We analyzed data from 190,949 African American, Native Hawaiian, Japanese American, Latino, and white individuals, 45 to 75 years old, who entered the Multiethnic Cohort study from 1993 through 1996. During an average 16 years of follow-up, 4770 invasive colorectal cancer cases were identified. Scores from all 4 DQIs associated inversely with colorectal cancer risk; higher scores associated with decreasing colorectal cancer risk (all P's for trend ≤ .003). Associations were not significant for AHEI-2010 and aMED scores in women after adjustment for covariates: for the highest vs lowest quintiles, the hazard ratio for the HEI-2010 score in men was 0.69 (95% confidence interval [CI], 0.59-0.80) and in women was 0.82 (95% CI, 0.70-0.96); for the AHEI-2010 score the hazard ratio in men was 0.75 (95% CI, 0.65-0.85) and in women was 0.90 (95% CI, 0.78-1.04); for the aMED score the hazard ratio in men was 0.84 (95% CI, 0.73-0.97) and in women was 0.96 (95% CI, 0.82-1.13); for the Dietary Approaches to Stop Hypertension score the hazard ratio in men was 0.75 (95% CI, 0.66-0.86) and in women was 0.86 (95% CI, 0.75-1.00). Associations were limited to the left colon and rectum for all indexes. The inverse associations were less strong in African American individuals than in the other 4 racial/ethnic groups. Based on an analysis of data from the Multiethnic Cohort Study, high-quality diets are associated with a lower risk of colorectal cancer in most racial/ethnic subgroups. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All

Systemic lupus erythematosus in three ethnic groups. XIV. Poverty, wealth, and their influence on disease activity.

PubMed

Alarcón, Graciela S; McGwin, Gerald; Sanchez, Martha L; Bastian, Holly M; Fessler, Barri J; Friedman, Alan W; Baethge, Bruce A; Roseman, Jeffrey; Reveille, John D

2004-02-15

To determine the impact of wealth on disease activity in the multiethnic (Hispanic, African American, and Caucasian) LUMINA (Lupus in Minorities, Nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) and disease duration < or =5 years at enrollment. Variables (socioeconomic, demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at enrollment and annually thereafter. Four questions from the Women's Health Initiative study were used to measure wealth. Disease activity was measured with the Systemic Lupus Activity Measure (SLAM). The relationship between the different variables and wealth was then examined. Next, the impact of wealth on disease activity was examined in regression models where the dependent variables were the SLAM score and SLAM global (physician). Variables previously found to impact disease activity plus the wealth questions were included in the models. Questions on income, assets, and debt were found to distinguish patients into groups, wealthier and less wealthy. Less wealthy patients tended to be younger, women, noncaucasian, less educated, unmarried, less likely to have health insurance, and more likely to live below the poverty line. They also tended to have more active disease, more abnormal illness-related behaviors, less social support, and lower levels of self reported mental functioning. None of the wealth questions was retained in the regression models, although other socioeconomic features (such as African American ethnicity, poverty, and younger age) did. Wealth, per se, does not appear to have an additional predictive value, over and above traditional measures of socioeconomic status, in SLE disease activity.

Hydroxychloroquine use in a community-based cohort of patients with systemic lupus erythematosus

PubMed Central

Schmajuk, Gabriela; Yazdany, Jinoos; Trupin, Laura; Yelin, Edward

2010-01-01

Background In recent years hydroxychloroquine (HCQ) has emerged as a key therapy in systemic lupus erythematosus (SLE). We determined the rates of HCQ use in a diverse, community-based cohort of patients with SLE and identified predictors of current HCQ use. Methods Patients were participants in the University of California San Francisco (UCSF) Lupus Outcomes Study (LOS), an ongoing longitudinal study of patients with confirmed SLE. We examined the prevalence of HCQ use per person-year and compared baseline characteristics of users and non-users, including demographic, socioeconomic, clinical, and health-system use variables. Multiple logistic regression with generalized estimating equations was used to evaluate predictors of HCQ use. Results Eight hundred and eighty one patients contributed 3095person-years of data over 4 interview cycles. The prevalence of HCQ use was 55 per 100 person-years and was constant throughout the observation period. In multivariate models, the odds of HCQ use were nearly doubled among patients receiving their SLE care from a rheumatologist compared to those identifying generalists or nephrologists as their primary sources of SLE care. In addition, patients with shorter disease duration were more likely to use HCQ, even after adjusting for age and other covariates. Conclusions In this community-based cohort of patients, HCQ use was suboptimal. Physician specialty and disease duration were the strongest predictors of HCQ use. Patients who are not using HCQ, those with longer disease duration, and those who see non-rheumatologists for their SLE care should be targeted for quality improvement. PMID:20391485

Burden of systemic lupus erythematosus on employment and work productivity: data from a large cohort in the southeastern United States.

PubMed

Drenkard, Cristina; Bao, Gaobin; Dennis, Greg; Kan, Hong J; Jhingran, Priti M; Molta, Charles T; Lim, S Sam

2014-06-01

To examine the burden of systemic lupus erythematosus (SLE) on work loss, unemployment, and work productivity impairment in an SLE cohort from the southeastern US. We examined 689 SLE patients ages 18-64 years from the Georgians Organized Against Lupus (GOAL) cohort. GOAL is a longitudinal cohort predominantly derived from the Georgia Lupus Registry, a population-based registry established in metropolitan Atlanta. We used the Kaplan-Meier method to assess the proportion of patients who self-reported work loss since diagnosis. We compared unemployment between SLE patients and the general population from the same geographic area, calculating the standardized unemployment ratio (SUR) within demographic and disease strata. We also calculated the percentage of work productivity impairment by disease outcomes. Of 511 patients employed at diagnosis, 249 (49%) experienced work loss within an average disease duration of 13 years. The proportion of patients who lost their jobs since diagnosis was almost twice for African Americans than for whites. However, the SURs were similar across demographic characteristics, including race. Patients with severe disease activity and severe organ damage had the highest SUR at 4.4 and 5.6, respectively. Among those that remained employed, patients with severe fatigue, neurocognitive symptoms, and musculoskeletal symptoms had the highest impairment of work productivity. SLE imposes a substantial toll on individuals and burden on society. Major factors that negatively impact work outcomes are fatigue, disease activity, and organ damage. More effective treatments along with coping strategies at the workplace are needed to reduce the burden of SLE on work outcomes. Copyright © 2014 by the American College of Rheumatology.

Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort

PubMed Central

Willis, R; Seif, AM; McGwin, G; Martinez-Martinez, LA; González, EB; Dang, N; Papalardo, E; Liu, J; Vilá, LM; Reveille, JD; Alarcón, GS; Pierangeli, SS

2013-01-01

Objective We sought to determine the effect of hydroxychloroquine therapy on the levels proinflammatory/prothrombotic markers and disease activity scores in patients with systemic lupus erythematosus (SLE) in a multiethnic, multi-center cohort (LUMINA). Methods Plasma/serum samples from SLE patients (n=35) were evaluated at baseline and after hydroxychloroquine treatment. Disease activity was assessed using SLAM-R scores. Interferon (IFN)-α2, interleukin (IL)-1β, IL-6, IL-8, inducible protein (IP)-10, monocyte chemotactic protein-1, tumor necrosis factor (TNF)-α and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Anticardiolipin antibodies were evaluated using ELISA assays. Thirty-two frequency-matched plasma/serum samples from healthy donors were used as controls. Results Levels of IL-6, IP-10, sCD40L, IFN-α and TNF-α were significantly elevated in SLE patients versus controls. There was a positive but moderate correlation between SLAM-R scores at baseline and levels of IFN-α (p=0.0546). Hydroxychloroquine therapy resulted in a significant decrease in SLAM-R scores (p=0.0157), and the decrease in SLAM-R after hydroxychloroquine therapy strongly correlated with decreases in IFN-α (p=0.0087). Conclusions Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE. PMID:22343096

Quality-of-life measurements in multiethnic patients with systemic lupus erythematosus: cross-cultural issues.

PubMed

Toloza, Sergio M A; Jolly, Meenakshi; Alarcón, Graciela S

2010-08-01

Although the survival rate for systemic lupus erythematosus (SLE) has improved dramatically during the past 50 years, the quality of life of patients afflicted with this disease remains poor. Currently existent measures of disease activity and damage in SLE do not capture the patient's perspective and health-related quality of life (HRQoL). Most studies in SLE pertaining to HRQoL are from developed Western societies, with only a few from others. These studies have been conducted predominantly in women and using the Medical Outcomes Survey Short Form 36, a generic HRQoL instrument that has been shown not to be sensitive to change in lupus. Existent lupus-specific HRQoL measures have not yet been used in SLE clinical trials. New HRQoL research tools are currently undergoing validation in different countries, languages, and cultural settings, which may help dissect the underlying role of socioeconomic status and specific disease-related features that impact SLE-related quality of life.

Genome-wide analysis of multiethnic cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

PubMed Central

Vitart, Veronique; Nag, Abhishek; Hewitt, Alex W; Höhn, René; Venturini, Cristina; Mirshahi, Alireza; Ramdas, Wishal D.; Thorleifsson, Gudmar; Vithana, Eranga; Khor, Chiea-Chuen; Stefansson, Arni B; Liao, Jiemin; Haines, Jonathan L; Amin, Najaf; Wang, Ya Xing; Wild, Philipp S; Ozel, Ayse B; Li, Jun Z; Fleck, Brian W; Zeller, Tanja; Staffieri, Sandra E; Teo, Yik-Ying; Cuellar-Partida, Gabriel; Luo, Xiaoyan; Allingham, R Rand; Richards, Julia E; Senft, Andrea; Karssen, Lennart C; Zheng, Yingfeng; Bellenguez, Céline; Xu, Liang; Iglesias, Adriana I; Wilson, James F; Kang, Jae H; van Leeuwen, Elisabeth M; Jonsson, Vesteinn; Thorsteinsdottir, Unnur; Despriet, Dominiek D.G.; Ennis, Sarah; Moroi, Sayoko E; Martin, Nicholas G; Jansonius, Nomdo M; Yazar, Seyhan; Tai, E-Shyong; Amouyel, Philippe; Kirwan, James; van Koolwijk, Leonieke M.E.; Hauser, Michael A; Jonasson, Fridbert; Leo, Paul; Loomis, Stephanie J; Fogarty, Rhys; Rivadeneira, Fernando; Kearns, Lisa; Lackner, Karl J; de Jong, Paulus T.V.M.; Simpson, Claire L; Pennell, Craig E; Oostra, Ben A; Uitterlinden, André G; Saw, Seang-Mei; Lotery, Andrew J; Bailey-Wilson, Joan E; Hofman, Albert; Vingerling, Johannes R; Maubaret, Cécilia; Pfeiffer, Norbert; Wolfs, Roger C.W.; Lemij, Hans G; Young, Terri L; Pasquale, Louis R; Delcourt, Cécile; Spector, Timothy D; Klaver, Caroline C.W.; Small, Kerrin S; Burdon, Kathryn P; Stefansson, Kari; Wong, Tien-Yin; Viswanathan, Ananth; Mackey, David A; Craig, Jamie E; Wiggs, Janey L; van Duijn, Cornelia M; Hammond, Christopher J; Aung, Tin

2014-01-01

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma and IOP variability may herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multiethnic participants for IOP. We confirm genetic association of known loci for IOP and primary open angle glaucoma (POAG) and identify four new IOP loci located on chromosome 3q25.31 within the FNDC3B gene (p=4.19×10−08 for rs6445055), two on chromosome 9 (p=2.80×10−11 for rs2472493 near ABCA1 and p=6.39×10−11 for rs8176693 within ABO) and one on chromosome 11p11.2 (best p=1.04×10−11 for rs747782). Separate meta-analyses of four independent POAG cohorts, totaling 4,284 cases and 95,560 controls, show that three of these IOP loci are also associated with POAG. PMID:25173106

Oral manifestations of lupus.

PubMed

Menzies, S; O'Shea, F; Galvin, S; Wynne, B

2018-02-01

Mucosal involvement is commonly seen in patients with lupus; however, oral examination is often forgotten. Squamous cell carcinoma arising within oral lupoid plaques has been described, emphasizing the importance of identifying and treating oral lupus. We undertook a retrospective single-centre study looking at oral findings in patients attending our multidisciplinary lupus clinic between January 2015 and April 2016. A total of 42 patients were included. The majority of patients were female (88%) and had a diagnosis of discoid lupus erythematosus (62%). Half of the patients had positive oral findings, 26% had no oral examination documented, and 24% had documented normal oral examinations. Our findings suggest that oral pathology is common in this cohort of patients. Regular oral examination is warranted to identify oral lupus and provide treatment. Associated diseases such as Sjogren's syndrome may also be identified. Patients should be encouraged to see their general dental practitioners on a regular basis for mucosal review. Any persistent ulcer that fails to respond to treatment or hard lump needs urgent histopathological evaluation to exclude malignant transformation to squamous cell carcinoma.

Risk of infective endocarditis in patients with systemic lupus erythematosus in Taiwan: a nationwide population-based study.

PubMed

Chang, Y S; Chang, C C; Chen, Y H; Chen, W S; Chen, J H

2017-10-01

Objectives Patients with systemic lupus erythematosus are considered vulnerable to infective endocarditis and prophylactic antibiotics are recommended before an invasive dental procedure. However, the evidence is insufficient. This nationwide population-based study evaluated the risk and related factors of infective endocarditis in systemic lupus erythematosus. Methods We identified 12,102 systemic lupus erythematosus patients from the National Health Insurance research-oriented database, and compared the incidence rate of infective endocarditis with that among 48,408 non-systemic lupus erythematosus controls. A Cox multivariable proportional hazards model was employed to evaluate the risk of infective endocarditis in the systemic lupus erythematosus cohort. Results After a mean follow-up of more than six years, the systemic lupus erythematosus cohort had a significantly higher incidence rate of infective endocarditis (42.58 vs 4.32 per 100,000 person-years, incidence rate ratio = 9.86, p < 0.001) than that of the control cohort. By contrast, the older systemic lupus erythematosus cohort had lower risk (adjusted hazard ratio 11.64) than that of the younger-than-60-years systemic lupus erythematosus cohort (adjusted hazard ratio 15.82). Cox multivariate proportional hazards analysis revealed heart disease (hazard ratio = 5.71, p < 0.001), chronic kidney disease (hazard ratio = 2.98, p = 0.034), receiving a dental procedure within 30 days (hazard ratio = 36.80, p < 0.001), and intravenous steroid therapy within 30 days (hazard ratio = 39.59, p < 0.001) were independent risk factors for infective endocarditis in systemic lupus erythematosus patients. Conclusions A higher risk of infective endocarditis was observed in systemic lupus erythematosus patients. Risk factors for infective endocarditis in the systemic lupus erythematosus cohort included heart disease, chronic kidney disease, steroid pulse therapy within 30 days, and a

Do classic blood biomarkers of JSLE identify active lupus nephritis? Evidence from the UK JSLE Cohort Study.

PubMed

Smith, E M D; Jorgensen, A L; Beresford, M W

2017-10-01

Background Lupus nephritis (LN) affects up to 80% of juvenile-onset systemic lupus erythematosus (JSLE) patients. The value of commonly available biomarkers, such as anti-dsDNA antibodies, complement (C3/C4), ESR and full blood count parameters in the identification of active LN remains uncertain. Methods Participants from the UK JSLE Cohort Study, aged <16 years at diagnosis, were categorized as having active or inactive LN according to the renal domain of the British Isles Lupus Assessment Group score. Classic biomarkers: anti-dsDNA, C3, C4, ESR, CRP, haemoglobin, total white cells, neutrophils, lymphocytes, platelets and immunoglobulins were assessed for their ability to identify active LN using binary logistic regression modeling, with stepAIC function applied to select a final model. Receiver-operating curve analysis was used to assess diagnostic accuracy. Results A total of 370 patients were recruited; 191 (52%) had active LN and 179 (48%) had inactive LN. Binary logistic regression modeling demonstrated a combination of ESR, C3, white cell count, neutrophils, lymphocytes and IgG to be best for the identification of active LN (area under the curve 0.724). Conclusions At best, combining common classic blood biomarkers of lupus activity using multivariate analysis provides a 'fair' ability to identify active LN. Urine biomarkers were not included in these analyses. These results add to the concern that classic blood biomarkers are limited in monitoring discrete JSLE manifestations such as LN.

Ethnic Admixture Affects Diabetes Risk in Native Hawaiians: The Multiethnic Cohort

PubMed Central

Maskarinec, Gertraud; Morimoto, Yukiko; Jacobs, Simone; Grandinetti, Andrew; Mau, Marjorie K.; Kolonel, Laurence N.

2016-01-01

Background/Objectives Obesity and diabetes rates are high in Native Hawaiians (NH) who commonly have mixed ancestries. Persons of Asian ancestry experience a high risk of type 2 diabetes despite the relatively low body weight. We evaluated the impact of ethnic admixture on diabetes risk among NH in the Multiethnic Cohort (MEC). Methods/Subjects Based on self-reports, 11,521 eligible men and women were categorized into NH/white, NH/other, NH alone, NH/Asian, and the most common three ancestry admixture, NH/Chinese/white. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the NH/white category as the reference group; covariates included known confounders, i.e., body mass index (BMI), dietary and other life-style factors. Results The NH alone category had the highest proportion of overweight and obese individuals and the NH/Asian category the lowest proportion. During 12 years of follow-up after cohort entry at 56 years, 2,072 incident cases were ascertained through questionnaires and health plan linkages. All NH categories had higher HRs than the NH/white category before and after adjustment for BMI. In fully-adjusted models, the NH/Asian category showed the highest risk (HR=1.45; 95%CI: 1.27–1.65), followed by NH/other (HR=1.20; 95%CI: 1.03–1.39), NH/Chinese/white (HR=1.19; 95%CI: 1.04–1.37), and NH alone (HR=1.19; 95%CI: 1.03–1.37). The elevated risk by Asian admixture was more pronounced in normal weight than overweight/obese individuals. Conclusions These findings indicate that Asian admixture in NHs is associated with higher risk for type 2 diabetes independent of known risk factors and suggest a role for ethnicity-related genetic factors in the development of this disease. PMID:27026423

The LupusQoL and associations with demographics and clinical measurements in patients with systemic lupus erythematosus.

PubMed

McElhone, Kathleen; Castelino, Madhura; Abbott, Janice; Bruce, Ian N; Ahmad, Yasmeen; Shelmerdine, Joanna; Peers, Kate; Isenberg, David; Ferenkeh-Koroma, Ada; Griffiths, Bridget; Akil, Mohammed; Maddison, Peter; Gordon, Caroline; Teh, Lee-Suan

2010-11-01

Having developed and validated a disease-specific health-related quality of life (HRQOL) measure for patients with systemic lupus erythematosus (SLE), the LupusQoL, we determined its relationship to demographic and clinical measurements in a group of patients with SLE. A group of 322 outpatients completed the LupusQoL. Demographic (age, sex, marital status, ethnicity) and clinical variables (disease duration, disease activity, damage) were recorded. Associations between the 8 LupusQoL domains and age, disease duration, disease activity, and damage were explored using Spearman's correlation coefficients. Differences in LupusQoL scores were examined for sex and marital status using the Mann-Whitney U test. Ethnic groups were compared using ANOVA. All domains of LupusQoL were impaired, with fatigue (56.3) being the worst affected and body image (80.0) the least. The correlations between the LupusQoL domain scores and age (r = -0.01 to -0.22) and disease duration (r = 0 to 0.16) were absent or weak. Similarly, there were no significant differences in the LupusQoL scores regarding sex, marital status, or the 3 main ethnic groups (Black-Caribbean, Asian, White). Although there were statistically significant correlations between the scores of the LupusQoL domains and some scores of the British Isles Lupus Assessment Group index (r = -0.22 to 0.09) and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (r = -0.29 to 0.21), these were weak. HRQOL was impaired in this cohort of outpatients with SLE as assessed by the validated lupus-specific LupusQoL. There were no clinically important associations between the 8 domains of the LupusQoL and clinical or demographic variables in this group of patients. Thus, the LupusQoL is a relatively independent outcome measure in patients with SLE.

Lack of recording of systemic lupus erythematosus in the death certificates of lupus patients.

PubMed

Calvo-Alén, J; Alarcón, G S; Campbell, R; Fernández, M; Reveille, J D; Cooper, G S

2005-09-01

To determine to what extent the diagnosis of systemic lupus erythematosus (SLE) in deceased lupus patients is under-reported in death certificates, and the patient characteristics associated with such an occurrence. The death certificates of 76 of the 81 deceased SLE patients from two US lupus cohorts (LUMINA for Lupus in Minorities: Nature vs Nurture and CLU for Carolina Lupus Study), including 570 and 265 patients, respectively, were obtained from the Offices of Vital Statistics of the states where the patients died (Alabama, Georgia, North Carolina, South Carolina, Tennessee and Texas). Both cohorts included patients with SLE as per the American College of Rheumatology criteria, aged > or =16 yr, and disease duration at enrolment of < or =5 yr. The median duration of follow-up in each cohort at the time of these analyses ranged from 38.1 to 53.0 months. Standard univariable analyses were performed comparing patients with SLE recorded anywhere in the death certificate and those without it. A multivariable logistic regression model was performed to identify the variables independently associated with not recording SLE in death certificates. In 30 (40%) death certificates, SLE was not recorded anywhere in the death certificate. In univariable analyses, older age was associated with lack of recording of SLE in death certificates [mean age (standard deviation) 50.9 (15.6) years and 39.1 (18.6) yr among those for whom SLE was omitted and included on the death certificates, respectively, P = 0.005]. Patients without health insurance, those dying of a cardiovascular event and those of Caucasian ethnicity were also more likely to be in the non-recorded group. In the multivariable analysis, variables independently associated with not recording SLE as cause of death were older age [odds ratio = (95% confidence interval) 1.043 (1.005-1.083 per yr increase); P = 0.023] and lack of health insurance [4.649 (1.152-18.768); P = 0.031]. A high proportion of SLE diagnoses are not

The systemic lupus erythematosus travel burden survey: baseline data among a South Carolina cohort.

PubMed

Williams, Edith M; Ortiz, Kasim; Zhang, Jiajia; Zhou, Jie; Kamen, Diane

2016-04-29

Many studies on the impact of systemic lupus erythematosus or lupus have identified patient travel costs as being problematic. We administered a survey that examined the impact of self-rated travel burden on lupus patients. The systemic lupus erythematosus travel burden survey included 41 patients enrolled in the systemic lupus erythematosus database project at the Medical University of South Carolina. Most participants reported that travel caused medications to be discontinued or appointments to be missed. In unadjusted logistic regressions of the relationship between these outcomes and medical travel burden, both distance to rheumatologists and time to lupus medical care were significant. Our findings suggest that more research is needed to examine the influence of travel burden among this population, but data from this report could help to inform physicians, academic researchers, and other health professionals in South Carolina and other areas with significant rural populations on how travel burden may impact patients receiving care for lupus and provide an opportunity for the development of interventions aimed at assisting lupus patients with management of stressors related to travel burden.

Disparity in Diabetes Risk across Native Hawaiians and Different Asian Groups: The Multiethnic Cohort

PubMed Central

Maskarinec, Gertraud; Jacobs, Simone; Morimoto, Yukiko; Chock, Marci; Grandinetti, Andrew; Kolonel, Laurence N.

2014-01-01

We evaluated the impact of body mass index (BMI) and lifestyle risk factors on ethnic disparity in diabetes incidence among 89,198 Asian, Native Hawaiian, and white participants of the Multiethnic Cohort who completed multiple questionnaires. After 12 years of follow-up, 11,218 new cases were identified through self-report and health plan linkages. BMI was lowest in Chinese/Koreans, Japanese, and Filipinos (22.4, 23.5, 23.9 kg/m2). Using Cox regression, the unadjusted hazard ratios were 1.9 (Chinese/Korean), 2.1 (Japanese, Mixed-Asian), 2.2 (Filipino), 2.5 (Native Hawaiian), and 2.6 (Part-Asian) as compared to whites. With BMI added, the risk for Japanese, Filipinos, Chinese/Koreans, and Mixed-Asians increased (8–42%) but declined in Part-Asians and Native Hawaiians (17–31%). When lifestyle and dietary factors were also included, the risk was attenuated in all groups (6–14%). Despite their lower BMI, Asian Americans have a higher diabetes risk than whites, but dietary and lifestyle factors do not account for the excess risk. PMID:25164594

Disparity in diabetes risk across Native Hawaiians and different Asian groups: the multiethnic cohort.

PubMed

Maskarinec, Gertraud; Jacobs, Simone; Morimoto, Yukiko; Chock, Marci; Grandinetti, Andrew; Kolonel, Laurence N

2015-05-01

We evaluated the impact of body mass index (BMI) and lifestyle risk factors on ethnic disparity in diabetes incidence among 89 198 Asian, Native Hawaiian, and white participants of the Multiethnic Cohort who completed multiple questionnaires. After 12 years of follow-up, 11 218 new cases were identified through self-report and health plan linkages. BMI was lowest in Chinese/Koreans, Japanese, and Filipinos (22.4, 23.5, and 23.9 kg/m(2)). Using Cox regression, the unadjusted hazard ratios were 1.9 (Chinese/Korean), 2.1 (Japanese, Mixed-Asian), 2.2 (Filipino), 2.5 (Native Hawaiian), and 2.6 (part-Asian) as compared with whites. With BMI added, the risk for Japanese, Filipinos, Chinese/Koreans, and mixed-Asians increased (8%-42%) but declined in part-Asians and Native Hawaiians (17%-31%). When lifestyle and dietary factors were also included, the risk was attenuated in all groups (6%-14%). Despite their lower BMI, Asian Americans have a higher diabetes risk than whites, but dietary and lifestyle factors do not account for the excess risk. © 2014 APJPH.

Association between the neighborhood obesogenic environment and colorectal cancer risk in the Multiethnic Cohort.

PubMed

Canchola, Alison J; Shariff-Marco, Salma; Yang, Juan; Albright, Cheryl; Hertz, Andrew; Park, Song-Yi; Shvetsov, Yurii B; Monroe, Kristine R; Le Marchand, Loïc; Gomez, Scarlett Lin; Wilkens, Lynne R; Cheng, Iona

2017-10-01

Information on the role of the neighborhood environment and colorectal cancer risk is limited. We investigated the association between a comprehensive suite of possible obesogenic neighborhood attributes (socioeconomic status, population density, restaurant and retail food environments, numbers of recreational facilities and businesses, commute patterns, traffic density, and street connectivity) and colorectal cancer risk in the Multiethnic Cohort Study. Among 81,197 eligible participants living in California (35,397 males and 45,800 females), 1973 incident cases (981 males and 992 females) of invasive colorectal cancer were identified between 1993 and 2010. Separately for males and females, multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer risk overall and by racial/ethnic group (African American, Japanese American, Latino, white). In males, higher traffic density was associated with an increased risk of colorectal cancer (HR=1.29, 95% CI: 1.03-1.61, p=0.03, for quintile 5 vs. quintile 1; p-trend=0.06). While this association may be due to chance, this pattern was seen (albeit non-statistically significant) in all racial/ethnic groups except whites. There were no other significant associations between other neighborhood obesogenic attributes and colorectal cancer risk. Findings from our large racial/ethnically diverse cohort suggest neighborhood obesogenic characteristics are not strongly associated with the risk of colorectal cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Maternal Dietary Patterns and Gestational Diabetes Mellitus in a Multi-Ethnic Asian Cohort: The GUSTO Study.

PubMed

de Seymour, Jamie; Chia, Airu; Colega, Marjorelee; Jones, Beatrix; McKenzie, Elizabeth; Shirong, Cai; Godfrey, Keith; Kwek, Kenneth; Saw, Seang-Mei; Conlon, Cathryn; Chong, Yap-Seng; Baker, Philip; Chong, Mary F F

2016-09-20

Gestational Diabetes Mellitus (GDM) is associated with an increased risk of perinatal morbidity and long term health issues for both the mother and offspring. Previous research has demonstrated associations between maternal diet and GDM development, but evidence in Asian populations is limited. The objective of our study was to examine the cross-sectional relationship between maternal dietary patterns during pregnancy and the risk of GDM in a multi-ethnic Asian cohort. Maternal diet was ascertained using 24-h dietary recalls from participants in the Growing up in Singapore towards healthy outcomes (GUSTO) study-a prospective mother-offspring cohort, and GDM was diagnosed according to 1999 World Health Organisation guidelines. Dietary patterns were identified using factor analysis, and multivariate regression analyses performed to assess the association with GDM. Of 909 participants, 17.6% were diagnosed with GDM. Three dietary patterns were identified: a vegetable-fruit-rice-based-diet, a seafood-noodle-based-diet and a pasta-cheese-processed-meat-diet. After adjusting for confounding variables, the seafood-noodle-based-diet was associated with a lower likelihood of GDM (Odds Ratio (95% Confidence Interval)) = 0.74 (0.59, 0.93). The dietary pattern found to be associated with GDM in our study was substantially different to those reported previously in Western populations.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

PubMed

Lewandowski, L B; Schanberg, L E; Thielman, N; Phuti, A; Kalla, A A; Okpechi, I; Nourse, P; Gajjar, P; Faller, G; Ambaram, P; Reuter, H; Spittal, G; Scott, C

2017-02-01

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage

Adult Height, Prevalent Coronary Artery Calcium Score, and Incident Cardiovascular Disease Outcomes in a Multiethnic Cohort.

PubMed

Yeboah, Joseph; Blaha, Michael J; Michos, Erin D; Qureshi, Waqas; Miedema, Michael; Flueckiger, Peter; Rodriguez, Carlos J; Szklo, Moyses; Bertoni, Alain G

2017-10-15

We assessed the relationships among adult height, coronary artery calcium (CAC) score, incident atherosclerotic cardiovascular disease (ASCVD) events, and atrial fibrillation (AFib) in a multiethnic cohort. We used race/ethnicity-specific height (dichotomized by median value and in quartiles) as the predictor variable within the 4 racial/ethnic groups in the Multi-Ethnic Study of Atherosclerosis (n = 6,814). After a mean of 10.2 years of follow-up (2000-2012), 556 ASCVD events (8.2%) and 539 AFib events (7.9%) occurred. Adult height was not associated with prevalent CAC score (ln(CAC + 1) or categories). Tall stature (i.e., race/ethnicity-specific height ≥median) had a significant but opposite association with future ASCVD and AFib (hazard ratios were 0.72 (95% confidence interval: 0.56, 0.92) and 1.38 (95% confidence interval: 1.07, 1.79), respectively). We observed a gradient-response but opposite association between quartiles of race/ethnicity-specific height and ASCVD/AFib events in our multivariable models. A formal test of interaction between race/ethnicity-specific height and sex was not significant in the ASCVD model (P = 0.78) but was significant in the AFib model (P = 0.03). Tall stature was associated (in a gradient-response fashion) with reduced risk of ASCVD events and increased risk of AFib. Adult height may signal interactions between genetic and environmental factors and may provide risk information independent of current traditional risk factors and CAC score. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Prospective Study of Lupus and Rheumatoid Arthritis in Relation to Deployment in Support of Iraq and Afghanistan: The Millennium Cohort Study

PubMed Central

Jones, Kelly A.; Granado, Nisara S.; Smith, Besa; Slymen, Donald J.; Ryan, Margaret A. K.; Boyko, Edward J.; Gackstetter, Gary D.; Phillips, Christopher J.; Smith, Tyler C.

2011-01-01

The objective of this study was to prospectively assess the association between deployment in support of the operations in Iraq and Afghanistan and newly reported lupus and rheumatoid arthritis while also considering the effects of demographic, behavioral, and occupational characteristics. A total of 77,047 (2001–2003) and 31,110 (2004–2006) participants completed the baseline Millennium Cohort questionnaire and were resurveyed approximately every 3 years. Longitudinal analyses were used to assess the adjusted association between deployment to Iraq and Afghanistan with and without combat exposures and newly reported disease. After adjusting, deployment was not significantly associated with newly reported lupus compared with nondeployers. However, compared with nondeployers, deployers with and without combat exposures were significantly less likely to newly report rheumatoid arthritis. Women, non-Hispanic black, and Hispanic participants had a significantly elevated risk for both diseases. Overall, deployment was not associated with an increased risk of newly reported lupus or rheumatoid arthritis. PMID:22162801

Sociodemographic correlates of cognition in the multi-ethnic study of atherosclerosis (MESA)

USDA-ARS?s Scientific Manuscript database

Our objective was to describe the methodology utilized to evaluate cognitive function in the Multi-Ethnic Study of Atherosclerosis (MESA) and to present preliminary results by age, sex, and race/ethnicity. Cross-sectional measurements of a prospective observational cohort. Residents of 6 U.S. commun...

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

PubMed

Morimoto, Y; Conroy, S M; Ollberding, N J; Kim, Y; Lim, U; Cooney, R V; Franke, A A; Wilkens, L R; Hernandez, B Y; Goodman, M T; Henderson, B E; Kolonel, L N; Le Marchand, L; Maskarinec, G

2014-11-01

Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution. In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case-control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry. In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P < 0.01), adiponectin was significantly lower in AA men and women (P = 0.02 and P < 0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P < 0.0001) and CRP (P = 0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status. These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation

Prospective Study of Alcohol Drinking, Smoking, and Pancreatitis: The Multiethnic Cohort.

PubMed

Setiawan, Veronica Wendy; Pandol, Stephen J; Porcel, Jacqueline; Wilkens, Lynne R; Le Marchand, Loïc; Pike, Malcolm C; Monroe, Kristine R

2016-07-01

We conducted a prospective analysis of 145,886 participants in the multiethnic cohort to examine the relationship of alcohol drinking and smoking with pancreatitis. Pancreatitis cases were categorized as gallstone-related acute pancreatitis (GSAP) (N = 1,065), non-GSAP (N = 1,222), and recurrent acute (RAP)/chronic pancreatitis (CP) (N = 523). We used the baseline questionnaire to identify alcohol intake and smoking history. Associations were estimated by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox models. Cigarette smoking was associated with non-GSAP and RAP/CP. Moderate alcohol intake was inversely associated with all types of pancreatitis in women (HRs, 0.66 to 0.81 for <1 drink per day), and with RAP/CP in men (HR, 0.57; 95% CI, 0.41-0.79 for <2 drinks per day). The risk of non-GS pancreatitis associated with current smoking was highest among men who consumed more than 4 drinks per day (HR, 2.06; 95% CI, 1.28-3.30), whereas among never smokers, moderate drinking was associated with a reduced risk (HR, 0.70; 95% CI, 0.51-0.96). In women, drinking less than 2 drinks per day was associated with a reduced risk of GSAP among never smokers (HR, 0.61; 95% CI, 0.46-0.80). Smoking is a risk factor for non-GS pancreatitis. Moderate alcohol intake is protective against all types of pancreatitis in women and against RAP/CP in men.

Gestational outcomes in patients with neuropsychiatric systemic lupus erythematosus.

PubMed

de Jesus, G R; Rodrigues, B C; Lacerda, M I; Dos Santos, F C; de Jesus, N R; Klumb, E M; Levy, R A

2017-04-01

This study analyzed maternal and fetal outcomes of pregnancies of neuropsychiatric systemic lupus erythematosus patients followed in a reference unit. This retrospective cohort study included 26 pregnancies of patients seen between 2011 and 2015 included with history and/or active neuropsychiatric systemic lupus erythematosus among 135 pregnancies. Three patients had active neuropsychiatric systemic lupus erythematosus at conception, but only one remained with neurological activity during gestation, characteristically related to the inadvertent suspension of medications. Twenty six percent of the newborns were small for gestational age and 40% of live births were premature, with no neonatal death or early complications of prematurity. Preeclampsia was diagnosed in nine pregnancies, with two cases of early severe form that resulted in intrauterine fetal death. Patients with neuropsychiatric systemic lupus erythematosus had more prematurity and preeclampsia compared to patients without neuropsychiatric disease. However, when concomitant lupus nephritis was excluded, the gestational results of neuropsychiatric systemic lupus erythematosus patients were more favorable.

Adherence to the food guide pyramid recommendations among African Americans and Latinos: results from the Multiethnic Cohort.

PubMed

Sharma, Sangita; Murphy, Suzanne P; Wilkens, Lynne R; Shen, Lucy; Hankin, Jean H; Monroe, Kristine R; Henderson, Brian; Kolonel, Laurence N

2004-12-01

The objective of the study was to determine the degree of adherence to the Food Guide Pyramid recommendations among African Americans, Latinos born in the United States, and Latinos born in Mexico. Subjects were from the Multiethnic Cohort Study in Hawaii and Los Angeles, and completed a self-administered quantitative food frequency questionnaire at baseline in 1993-1996. Dairy recommendations were the least likely of all the food group recommendations to be followed, with 61% to 99% of individuals in the three ethnic groups not consuming the recommended number of servings. African Americans were less likely to adhere to all of the food group recommendations compared to the two Latino groups. A greater percentage of Latinos born in the United States did not adhere to the food group recommendations compared to Latinos born in Mexico. All three groups would benefit from interventions designed to promote healthy food choices.

The effects of rituximab on the lipid profile of patients with active systemic lupus erythematosus: results from a nationwide cohort in Spain (LESIMAB).

PubMed

Fernández-Nebro, A; Marenco, J L; López-Longo, F; Galindo, M; Hernández-Cruz, B E; Narváez, J; Rúa-Figueroa, I; Raya-Alvarez, E; Zea, A; Freire, M; Sánchez-Atrio, A I; García-Vicuña, R; Pego-Reigosa, J M; Manrique-Arija, S; Nieves-Martín, L; Carreño, L

2014-09-01

Patients with systemic lupus erythematosus (SLE) have increased cardiovascular risk related to lipid changes induced by inflammatory activity, proteinuria and treatments. Our objective was to analyse lipid changes in a cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The study population comprised a retrospective multicentre, national cohort of patients with SLE resistant to standard treatments who were treated with rituximab. The basic lipid profile, concomitant treatment and disease activity were analysed at the start of the treatment, 24 weeks later, and at the end of the follow-up period. The effects of the main lupus variables and therapy on the lipid changes were analysed. Seventy-nine patients with active lupus treated with rituximab were assessed during 149.3 patient-years. Prior to the treatment, 69% had dyslipidaemia. The most frequent abnormalities were a low-density lipoprotein (LDL) level of ≥100 mg/dl (34%) and a high-density lipoprotein (HDL) level of <50 mg/dl (27%). Baseline total cholesterol (TC) and LDL levels correlated with the degree of proteinuria, while the concentration of triglycerides (TGs) correlated with the SLE Disease Activity Index (SLEDAI). TGs were reduced at short- and long-term follow-up after rituximab treatment. A multiple linear regression analysis identified that the reduction of the lupus inflammatory activity, particularly changes in proteinuria, was the only independent variable that was positively associated with the reduction in TGs after 24 weeks (p=0.001) and with TC (p=0.005) and TGs (p<0.001) at the end of the follow-up period. Our results suggest that rituximab may improve the long-term lipid profile of patients with SLE refractory to standard treatment, mainly by reducing inflammatory activity. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Clinical characteristics during diagnosis of a prospective cohort of patients with systemic lupus erythematosus treated in Spanish Departments of Internal Medicine: The RELES study.

PubMed

Canora, J; García, M; Mitjavila, F; Espinosa, G; Suárez, S; González-León, R; Sopeña, B; Boldova, R; Castro, A; Ruiz-Irastorza, G

Patient registries are useful tools for assessing rare diseases. Our objective is to present the Spanish registry of patients with systemic lupus erythematosus (Registro español de pacientes con lupus eritematoso sistémico, RELES). RELES was started in 2008 as an observational, prospective, multicentre cohort registry that included patients from the time they were diagnosed. The registry's objective is to analyse the incidence and noninflammatory complications of systemic lupus erythematosus (SLE). The departments of internal medicine of 38 Spanish hospitals participate in this registry. A total of 298 patients with a mean age of 40.8±15.7 years were included, 88.9% of whom were women and 85.6% of whom were white. In the first visit, there was a predominance of joint manifestations (74.5%). One hundred and seventy-seven patients (59.4%) were positive for anti-native DNA. In these patients, there was a higher rate of lupus nephritis (26.7% vs. 14%, p=.009; relative risk [RR], 1.33), haemolytic anaemia (13.6% vs. 4.1%, p=.07; RR, 1.46) and lymphopenia (55.4% vs. 43.8%, p=.05; RR, 1.21). The median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K) score was 9.64 points (interquartile range, 4-13). The patients treated with antimalarial drugs before the diagnosis of SLE had a median SLEDAI score in the first visit of 5, compared with 8 for those who were not treated with these drugs (p=.02). RELES constitutes the first Spanish patient cohort with SLE recorded from the time of the diagnosis. The presence of anti-DNA has been related to severe manifestations such as nephritis and haemolytic anaemia. Treatment with antimalarial drugs before the diagnosis was associated with less active disease at the initial presentation. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Systemic Lupus Erythematosus (Lupus)

MedlinePlus

... lupus treatment. Treatment generally consists of a team approach. Learning to recognize the warning signs of a flare can help with reducing or preventing the flares. Systemic lupus erythematosus (lupus) happens when the body’s defense ...

Predictors of long-term renal outcome in lupus nephritis trials: lessons learned from the Euro-Lupus Nephritis cohort.

PubMed

Dall'Era, Maria; Cisternas, Miriam G; Smilek, Dawn E; Straub, Laura; Houssiau, Frédéric A; Cervera, Ricard; Rovin, Brad H; Mackay, Meggan

2015-05-01

There is a need to determine which response measures in lupus nephritis trials are most predictive of good long-term renal function. We used data from the Euro-Lupus Nephritis Trial to evaluate the performance of proteinuria, serum creatinine (Cr), and urinary red blood cells (RBCs) as predictors of good long-term renal outcome. Patients from the Euro-Lupus Nephritis Trial with proteinuria, serum Cr, and urinary RBC measurements at 3, 6, or 12 months and with a minimum of 7 years of followup were included (n = 76). We assessed the ability of these clinical biomarkers at 3, 6, and 12 months after randomization to predict good long-term renal outcome (defined as a serum Cr value ≤1.0 mg/dl) at 7 years. Receiver operating characteristic curves were generated to assess parameter performance at these time points and to select the best cutoff for individual parameters. Sensitivity and specificity were calculated for the parameters alone and in combination. A proteinuria value of <0.8 gm/day at 12 months after randomization was the single best predictor of good long-term renal function (sensitivity 81% and specificity 78%). The addition of serum Cr to proteinuria as a composite predictor did not improve the performance of the outcome measure; addition of urinary RBCs as a predictor significantly decreased the sensitivity to 47%. This study demonstrates that the level of proteinuria at 12 months is the individual best predictor of long-term renal outcome in patients with lupus nephritis. Inclusion of urinary RBCs as part of a composite outcome measure actually undermined the predictive value of the trial data. We therefore suggest that urinary RBCs should not be included as a component of clinical trial response criteria in lupus nephritis. © 2015, American College of Rheumatology.

Lupus

MedlinePlus

... Staying Safe Videos for Educators Search English Español Lupus KidsHealth / For Teens / Lupus What's in this article? ... dad that she might have lupus. What Is Lupus? Lupus (pronounced: LOO-pus) is a disease that ...

The rate of and risk factors for frequent hospitalization in systemic lupus erythematosus: results from the Korean lupus network registry.

PubMed

Lee, J W; Park, D J; Kang, J H; Choi, S E; Yim, Y R; Kim, J E; Lee, K E; Wen, L; Kim, T J; Park, Y W; Sung, Y K; Lee, S S

2016-11-01

Objectives The survival rate of patients with systemic lupus erythematosus has improved in the last few decades, but the rate of hospitalization and health care costs for these patients remain higher than in the general population. Thus, we evaluated the rate of hospitalization and associated risk factors in an inception cohort of Korean patients with lupus. Methods Of the 507 patients with systemic lupus erythematosus enrolled in the KORean lupus NETwork, we investigated an inception cohort consisting of 196 patients with systemic lupus erythematosus presenting within 6 months of diagnosis based on the American College of Rheumatology classification criteria. We evaluated the causes of hospitalization, demographic characteristics, and laboratory and clinical data at the time of systemic lupus erythematosus diagnosis of hospitalized patients and during a follow-up period. We calculated the hospitalization rate as the number of total hospitalizations divided by the disease duration, and defined "frequent hospitalization" as hospitalization more than once per year. Results Of the 196 patients, 117 (59.6%) were admitted to hospital a total of 257 times during the 8-year follow-up period. Moreover, 22 (11.2%) patients were hospitalized frequently. The most common reasons for hospitalization included disease flares, infection, and pregnancy-related morbidity. In the univariate regression analysis, malar rash, arthritis, pericarditis, renal involvement, fever, systemic lupus erythematosus disease activity index > 12, hemoglobin level < 10 mg/dl, albumin level < 3.5 mg/dl, and anti-Sjögren's syndrome A positivity were associated with frequent hospitalization. Finally, multivariate analysis showed that arthritis, pericarditis, and anti-Sjögren's syndrome A antibody positivity at the time of diagnosis were risk factors for frequent hospitalization. Conclusions Our results showed that frequent hospitalization occurred in 11.2% of hospitalized patients and

Economic evaluation of lupus nephritis in the Systemic Lupus International Collaborating Clinics inception cohort using a multistate model approach.

PubMed

Barber, Megan R W; Hanly, John G; Su, Li; Urowitz, Murray B; Pierre, Yvan St; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Wallace, Daniel J; Isenberg, David A; Rahman, Anisur; Ginzler, Ellen M; Petri, Michelle; Bruce, Ian N; Fortin, Paul R; Gladman, Dafna D; Sanchez-Guerrero, Jorge; Ramsey-Goldman, Rosalind; Khamashta, Munther A; Aranow, Cynthia; Mackay, Meggan; Alarcón, Graciela S; Manzi, Susan; Nived, Ola; Jönsen, Andreas; Zoma, Asad A; van Vollenhoven, Ronald F; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Sam Lim, S; Kalunian, Kenneth C; Inanc, Murat; Kamen, Diane L; Peschken, Christine A; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Farewell, Vernon; Clarke, Ann E

2017-11-28

Little is known about the long-term costs of lupus nephritis (LN). These were compared between patients with and without LN based on multistate modelling. Patients from 32 centres in 11 countries were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis and provided annual data on renal function, hospitalizations, medications, dialysis, and selected procedures. LN was diagnosed by renal biopsy or the American College of Rheumatology classification criteria. Renal function was assessed annually using estimated glomerular filtration rate (eGFR) or proteinuria (ePrU). A multistate model was used to predict 10-year cumulative costs by multiplying annual costs associated with each renal state by the expected state duration. 1,545 patients participated, 89.3% female, mean age at diagnosis 35.2 years (SD 13.4), 49.0% Caucasian, and mean follow up 6.3 years (SD 3.3). LN developed in 39.4% by the end of follow up. Ten-year cumulative costs were greater in those with LN and an eGFR < 30 ml/min ($310 579 2015 Canadian dollars versus $19 987 if no LN and eGFR > 60 ml/min) or with LN and ePrU > 3 g/d ($84 040 versus $20 499 if no LN and ePrU < 0.25 g/d). Patients with eGFR < 30 ml/min incurred 10-year costs 15-fold higher than those with normal eGFR. By estimating the expected duration in each renal state and incorporating associated annual costs, disease severity at presentation can be used to anticipate future healthcare costs. This is critical knowledge for cost-effectiveness evaluations of novel therapies. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

The number of flares patients experience impacts on damage accrual in systemic lupus erythematosus: data from a multiethnic Latin American cohort.

PubMed

Ugarte-Gil, Manuel F; Acevedo-Vásquez, Eduardo; Alarcón, Graciela S; Pastor-Asurza, Cesar A; Alfaro-Lozano, José L; Cucho-Venegas, Jorge M; Segami, Maria I; Wojdyla, Daniel; Soriano, Enrique R; Drenkard, Cristina; Brenol, João Carlos; de Oliveira e Silva Montandon, Ana Carolina; Costallat, Lilian T Lavras; Massardo, Loreto; Molina-Restrepo, José F; Guibert-Toledano, Marlene; Silveira, Luis H; Amigo, Mary Carmen; Barile-Fabris, Leonor A; Chacón-Díaz, Rosa; Esteva-Spinetti, Maria H; Pons-Estel, Guillermo J; McGwin, Gerald; Pons-Estel, Bernardo A

2015-06-01

To determine the association between the number of flares systemic lupus erythematosus (SLE) patients experience and damage accrual, independently of other known risk factors. SLE patients (34 centres, nine Latin American countries) with a recent diagnosis (≤2 years) and ≥3 evaluations were studied. Disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and damage with the SLICC/ACR Damage Index (SDI). Flare was defined as an increase ≥4 points in the SLEDAI between two study visits. An ambidirectional case- crossover design was used to determine the association between the number of flares and damage accrual. 901 patients were eligible for the study; 500 of them (55.5%) experienced at least one flare, being the mean number of flares 0.9 (SD: 1.0). 574 intervals from 251 patients were included in the case-crossover design since they have case and control intervals, whereas, the remaining patients did not. Their mean age at diagnosis was 27.9 years (SD: 11.1), 213 (84.9%) were women. The mean baseline SDI and SLEDAI were 1.3 (1.3) and 13.6 (8.1), respectively. Other features were comparable to those of the entire sample. After adjusting for possible confounding variables, the number of flares, regardless of their severity, was associated with damage accrual (SDI) OR 2.05, 95% CI 1.43 to 2.94, p<0.001 (OR 2.62, 95% CI 1.31 to 5.24, p=0.006 for severe and OR 1.91, 95% CI 1.28 to 2.83, p=0.001 for mild-moderate). The number of flares patients experience, regardless of their severity, increases the risk of damage accrual, independently of other known risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa

PubMed Central

Lewandowski, Laura B; Schanberg, Laura E; Thielman, Nathan; Phuti, Angel; Kalla, Asgar A; Okpechi, Ikechi; Nourse, Peter; Gajjar, Priya; Faller, Gail; Ambaram, Priya; Reuter, Helmuth; Spittal, Graeme; Scott, Christiaan

2016-01-01

Background Systemic Lupus Erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE (pSLE) on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa (SA). Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serologic characteristics was extracted from medical records. Results were compared to a well-described North American pSLE cohort. Results Seventy-two SA patients were enrolled in the study; mean age 11.5 years, 82% female. The racial distribution was 68% Coloured, 24% Black, 5% White, and 3% Asian/Indian. Most patients presented with severe lupus nephritis (LN) documented by renal biopsy (61%). Of patients with LN, 63% presented with International Society of Nephrology/Renal Pathology Society (ISN/RPS) class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate, and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K [SLEDAI-2K] 20.6). The SLEDAI-2K at enrollment in the PULSE cohort (5.0) did not differ from the North American pSLE cohort (4.8). Sixty three % of PULSE cohort had end organ damage with System Lupus International Collaborating Clinic-Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, 9 (13%) developed ESRD with 6 (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrollment in the SA registry. SA patients have

High mortality due to sepsis in Native Hawaiians and African Americans: The Multiethnic Cohort.

PubMed

Matter, Michelle L; Shvetsov, Yurii B; Dugay, Chase; Haiman, Christopher A; Le Marchand, Loic; Wilkens, Lynne R; Maskarinec, Gertraud

2017-01-01

Sepsis is a severe systemic response to infection with a high mortality rate. A higher incidence has been reported for older people, in persons with a compromised immune system including cancer patients, and in ethnic minorities. We analyzed sepsis mortality and its predictors by ethnicity in the Multiethnic Cohort (MEC). Among 191,561 white, African American, Native Hawaiian, Japanese American, and Latino cohort members, 49,347 deaths due to all causes and 345 deaths due to sepsis were recorded during follow-up from 1993-96 until 2010. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for relevant confounders. In addition, national death rates were analyzed to compare mortality by state. Age-adjusted rates of sepsis death were 5-times higher for Hawaii than Los Angeles (14.4 vs. 2.7 per 100,000). By ethnicity, Native Hawaiians had the highest rate in Hawaii (29.0 per 100,000) and African Americans in Los Angeles (5.2 per 100,000). In fully adjusted models, place of residence was the most important predictor of sepsis mortality (HR = 7.18; 95%CI: 4.37-11.81 Hawaii vs. Los Angeles). African Americans showed the highest risk (HR = 2.08; 95% CI: 1.16-3.75) followed by Native Hawaiians (HR = 1.88; 95% CI: 1.34-2.65) as compared to whites. Among cohort members with cancer (N = 49,794), the 2-fold higher sepsis mortality remained significant in Native Hawaiians only. The geographic and ethnic differences in the MEC agreed with results for national death data. The finding that African Americans and Native Hawaiians experience a higher mortality risk due to sepsis than other ethnic groups suggest ethnicity-related biological factors in the predisposition of cancer patients and other immune-compromising conditions to develop sepsis, but regional differences in health care access and death coding may also be important.

High mortality due to sepsis in Native Hawaiians and African Americans: The Multiethnic Cohort

PubMed Central

Shvetsov, Yurii B.; Dugay, Chase; Haiman, Christopher A.; Le Marchand, Loic; Wilkens, Lynne R.; Maskarinec, Gertraud

2017-01-01

Background/Objectives Sepsis is a severe systemic response to infection with a high mortality rate. A higher incidence has been reported for older people, in persons with a compromised immune system including cancer patients, and in ethnic minorities. We analyzed sepsis mortality and its predictors by ethnicity in the Multiethnic Cohort (MEC). Subjects/Methods Among 191,561 white, African American, Native Hawaiian, Japanese American, and Latino cohort members, 49,347 deaths due to all causes and 345 deaths due to sepsis were recorded during follow-up from 1993–96 until 2010. Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for relevant confounders. In addition, national death rates were analyzed to compare mortality by state. Results Age-adjusted rates of sepsis death were 5-times higher for Hawaii than Los Angeles (14.4 vs. 2.7 per 100,000). By ethnicity, Native Hawaiians had the highest rate in Hawaii (29.0 per 100,000) and African Americans in Los Angeles (5.2 per 100,000). In fully adjusted models, place of residence was the most important predictor of sepsis mortality (HR = 7.18; 95%CI: 4.37–11.81 Hawaii vs. Los Angeles). African Americans showed the highest risk (HR = 2.08; 95% CI: 1.16–3.75) followed by Native Hawaiians (HR = 1.88; 95% CI: 1.34–2.65) as compared to whites. Among cohort members with cancer (N = 49,794), the 2-fold higher sepsis mortality remained significant in Native Hawaiians only. The geographic and ethnic differences in the MEC agreed with results for national death data. Conclusions The finding that African Americans and Native Hawaiians experience a higher mortality risk due to sepsis than other ethnic groups suggest ethnicity-related biological factors in the predisposition of cancer patients and other immune-compromising conditions to develop sepsis, but regional differences in health care access and death coding may also be important. PMID:28558016

Mediterranean diet and brain structure in a multiethnic elderly cohort

PubMed Central

Brickman, Adam M.; Stern, Yaakov; Habeck, Christian G.; Razlighi, Qolamreza R.; Luchsinger, José A.; Manly, Jennifer J.; Schupf, Nicole; Mayeux, Richard; Scarmeas, Nikolaos

2015-01-01

Objective: To determine whether higher adherence to a Mediterranean-type diet (MeDi) is related with larger MRI-measured brain volume or cortical thickness. Methods: In this cross-sectional study, high-resolution structural MRI was collected on 674 elderly (mean age 80.1 years) adults without dementia who participated in a community-based, multiethnic cohort. Dietary information was collected via a food frequency questionnaire. Total brain volume (TBV), total gray matter volume (TGMV), total white matter volume (TWMV), mean cortical thickness (mCT), and regional volume or CT were derived from MRI scans using FreeSurfer program. We examined the association of MeDi (scored as 0–9) and individual food groups with brain volume and thickness using regression models adjusted for age, sex, ethnicity, education, body mass index, diabetes, and cognition. Results: Compared to lower MeDi adherence (0–4), higher adherence (5–9) was associated with 13.11 (p = 0.007), 5.00 (p = 0.05), and 6.41 (p = 0.05) milliliter larger TBV, TGMV, and TWMV, respectively. Higher fish (b = 7.06, p = 0.006) and lower meat (b = 8.42, p = 0.002) intakes were associated with larger TGMV. Lower meat intake was also associated with larger TBV (b = 12.20, p = 0.02). Higher fish intake was associated with 0.019 mm (p = 0.03) larger mCT. Volumes of cingulate cortex, parietal lobe, temporal lobe, and hippocampus and CT of the superior-frontal region were associated with the dietary factors. Conclusions: Among older adults, MeDi adherence was associated with less brain atrophy, with an effect similar to 5 years of aging. Higher fish and lower meat intake might be the 2 key food elements that contribute to the benefits of MeDi on brain structure. PMID:26491085

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

PubMed

Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a

Secular Trends in the Incidence of Dementia in a Multi-Ethnic Community.

PubMed

Noble, James M; Schupf, Nicole; Manly, Jennifer J; Andrews, Howard; Tang, Ming-Xin; Mayeux, Richard

2017-10-03

Determination of secular trends in cognitive aging is important for prioritization of resources, services, and research in aging populations. Prior studies have identified declining dementia incidence associated with changes in cardiovascular risk factors and increased educational attainment. However, few studies have examined these factors in multi-ethnic cohorts. To identify secular trends in the incidence rate of dementia in an elderly population. Participants in this study were drawn from the Washington Heights-Inwood Columbia Aging Project, a multi-ethnic cohort study of northern Manhattan residents aged 65 years and older. Cox proportional hazards models were used to examine differences in the incidence of dementia in cohorts recruited in 1992 and 1999, with age at dementia or age at last follow-up visit as the "time-to-event" variable. Overall, there was a 41% reduction in the hazard ratio for dementia among participants in the 1999 cohort compared with those in the 1992 cohort, adjusting for age, sex, race, and baseline memory complaints (HR = 0.59). The reduction in incidence was greatest among non-Hispanic Whites and African-Americans and lowest among Hispanic participants (HRs = 0.60, 0.52 and 0.64, respectively), and was associated with increases in level of educational attainment, especially among African-Americans. Reduction in incidence of dementia was also greater among persons 75 years or older than among younger participants (HR = 0.52 versus HR = 0.69). Our results support previous findings that secular trends in dementia incidence are changing, including in aging minority populations.

Associations Between Genetic Ancestries and Nicotine Metabolism Biomarkers in the Multiethnic Cohort Study

PubMed Central

Wang, Hansong; Park, Sungshim L.; Stram, Daniel O.; Haiman, Christopher A.; Wilkens, Lynne R.; Hecht, Stephen S.; Kolonel, Laurence N.; Murphy, Sharon E.; Le Marchand, Loïc

2015-01-01

Differences in internal dose of nicotine and tobacco-derived carcinogens among ethnic/racial groups have been observed. In this study, we explicitly examined the relationships between genetic ancestries (genome-wide average) and 19 tobacco-derived biomarkers in smokers from 3 admixed groups in the Multiethnic Cohort Study (1993–present), namely, African ancestry in African Americans (n = 362), Amerindian ancestry in Latinos (n = 437), and Asian and Native Hawaiian ancestries in Native Hawaiians (n = 300). After multiple comparison adjustment, both African and Asian ancestries were significantly related to a greater level of free cotinine; African ancestry was also significantly related to lower cotinine glucuronidation (P's < 0.00156). The predicted decrease in cotinine glucuronidation was 8.6% (P = 4.5 × 10−6) per a 20% increase in African ancestry. Follow-up admixture mapping revealed that African ancestry in a 12-Mb region on chromosome 4q was related to lower cotinine glucuronidation (P's < 2.7 × 10−7, smallest P = 1.5 × 10−9), although this is the same region reported in our previous genome-wide association study. Our results implicate a genetic ancestral component in the observed ethnic/racial variation in nicotine metabolism. Further studies are needed to identify the underlying genetic variation that could potentially be ethnic/racial specific. PMID:26568573

Premature atherosclerosis in pediatric systemic lupus erythematosus: risk factors for increased carotid intima-media thickness in the atherosclerosis prevention in pediatric lupus erythematosus cohort.

PubMed

Schanberg, Laura E; Sandborg, Christy; Barnhart, Huiman X; Ardoin, Stacy P; Yow, Eric; Evans, Gregory W; Mieszkalski, Kelly L; Ilowite, Norman T; Eberhard, Anne; Levy, Deborah M; Kimura, Yukiko; von Scheven, Emily; Silverman, Earl; Bowyer, Suzanne L; Punaro, Lynn; Singer, Nora G; Sherry, David D; McCurdy, Deborah; Klein-Gitelman, Marissa; Wallace, Carol; Silver, Richard; Wagner-Weiner, Linda; Higgins, Gloria C; Brunner, Hermine I; Jung, Lawrence; Soep, Jennifer B; Reed, Ann

2009-05-01

To evaluate risk factors for subclinical atherosclerosis in a population of patients with pediatric systemic lupus erythematosus (SLE). In a prospective multicenter study, a cohort of 221 patients underwent baseline measurements of carotid intima-media thickness (CIMT) as part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) trial. SLE disease measures, medications, and traditional risk factors for atherosclerosis were assessed. A standardized protocol was used to assess the thickness of the bilateral common carotid arteries and the mean maximal IMT of 12 segments. Univariable analysis identified potential associations with CIMT, which were examined in multivariable linear regression modeling. Based on the mean-mean common or the mean-max CIMT as the dependent variable, univariable analysis showed significant associations of the following variables with increased CIMT: increasing age, longer SLE duration, minority status, higher body mass index (BMI), male sex, increased creatinine clearance, higher lipoprotein(a) level, proteinuria, azathioprine treatment, and prednisone dose. In multivariable modeling, both azathioprine use (P=0.005 for the mean-mean model and P=0.102 for the mean-max model) and male sex (P<0.001) were associated with increases in the mean-max CIMT. A moderate dosage of prednisone (0.15-0.4 mg/kg/day) was associated with decreases in the mean-max CIMT (P=0.024), while high-dose and low-dose prednisone were associated with increases in the mean-mean common CIMT (P=0.021) and the mean-max CIMT (P=0.064), respectively. BMI (P<0.001) and creatinine clearance (P=0.031) remained associated with increased mean-mean common CIMT, while increasing age (P<0.001) and increasing lipoprotein(a) level (P=0.005) were associated with increased mean-max CIMT. Traditional as well as nontraditional risk factors were associated with increased CIMT in this cohort of patients in the APPLE trial. Azathioprine treatment was associated with

The African Lupus Genetics Network (ALUGEN) registry: standardized, prospective follow-up studies in African patients with systemic lupus erythematosus.

PubMed

Hodkinson, B; Mapiye, D; Jayne, D; Kalla, A; Tiffin, N; Okpechi, I

2016-03-01

The prevalence and severity of systemic lupus erythematosus (SLE) differs between ethnic groups and geographical regions. Although initially reported as rare, there is growing evidence that SLE is prevalent and runs a severe course in Africa. There is a paucity of prospective studies on African SLE patients. The African Lupus Genetics Network (ALUGEN) is a multicentred framework seeking to prospectively assess outcomes in SLE patients in Africa. Outcomes measured will be death, hospital admission, disease activity flares, and SLE-related damage. We will explore predictors for these outcomes including clinical, serological, socio-demographic, therapeutic and genetic factors. Further, we will investigate comorbidities and health-related quality of life amongst these patients. Data of patients recently (≤ 5 yrs) diagnosed with SLE will be collected at baseline and annual follow-up visits, and captured electronically. The ALUGEN project will facilitate standardized data capture for SLE cases in Africa, allowing participating centres to develop their own SLE registries, and enabling collaboration to enrich our understanding of inter-ethnic and regional variations in disease expression. Comprehensive, high-quality multi-ethnic data on African SLE patients will expand knowledge of the disease and inform clinical practice, in addition to augmenting research capacity and networking links and providing a platform for future biomarker and interventional studies. © The Author(s) 2015.

Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

2012-10-01

Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if self-reported early menopause (menopause at an age <46 y) identifies women as at risk for future coronary heart disease or stroke. The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000-2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46 y) and future coronary heart disease and stroke was assessed in 2,509 women (ages 45-84 y; 987 white, 331 Chinese, 641 black, and 550 Hispanic) from the Multi-ethnic Study Atherosclerosis who were free of cardiovascular disease at baseline. Of 2,509 women, 693 (28%) reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank P = 0.008 and P = 0.0158). In models adjusted for age, race/ethnicity, Multi-ethnic Study Atherosclerosis site, and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (hazard ratio, 2.08; 95% CI, 1.17-3.70; and hazard ratio, 2.19; 95% CI, 1.11-4.32, respectively). Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors.

Diabetic Retinopathy in a Multi-ethnic Cohort in the United States

PubMed Central

WONG, TIEN YIN; KLEIN, RONALD; ISLAM, F.M. AMIRUL; COTCH, MARY FRANCES; FOLSOM, AARON R.; KLEIN, BARBARA E.K.; SHARRETT, A. RICHEY; SHEA, STEVEN

2008-01-01

PURPOSE To describe the prevalence and risk factors of diabetic retinopathy in a multi-ethnic US population of whites, blacks, hispanics, and chinese. DESIGN Cross-sectional study of 778 individuals from ages 45 to 85 years with diabetes, participating in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS Retinal photographs were obtained with a 45° nonmydriatic digital fundus camera. Presence and severity of diabetic retinopathy were graded at a central reading center on the basis of a modification of the Airlie House classification system. All participants underwent a standardized interview, examination, and laboratory investigations. RESULTS In this population with diabetes, the prevalence of any retinopathy was 33.2% and macular edema 9.0%. The prevalence of any diabetic retinopathy and macular edema was significantly higher in blacks (36.7% and 11.1%) and hispanics (37.4% and 10.7%) than in whites (24.8% and 2.7%) and chinese (25.7% and 8.9%) (P = .01 and P = .007, comparing racial/ethnic differences for retinopathy and macular edema, respectively). Significant independent predictors of any retinopathy were longer duration of diabetes, higher fasting serum glucose, use of diabetic oral medication or insulin, and greater waist-hip ratio. Race was not an independent predictor of any retinopathy. CONCLUSIONS This study provides contemporary data on the prevalence of and risk factors for diabetic retinopathy among whites, blacks, hispanics, and chinese participating in the MESA. PMID:16490489

Prediagnostic serum tocopherol levels and the risk of non-hodgkin lymphoma: the multiethnic cohort.

PubMed

Morimoto, Yukiko; Ollberding, Nicholas J; Cooney, Robert V; Wilkens, Lynne R; Franke, Adrian A; Le Marchand, Loïc; Goodman, Marc T; Hernandez, Brenda Y; Kolonel, Laurence N; Maskarinec, Gertraud

2013-11-01

Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high-pressure liquid chromatography/photodiode array detection with NHL risk. Conditional logistic regression was used to calculate ORs and 95% confidence intervals (CI). We observed U-shaped associations with NHL for total and α-tocopherols [Ptrend < 0.01 for polynomial terms (3 df)]. The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25-0.68), 0.52 (0.32-0.85), 0.39 (0.23-0.65), and 0.78 (0.47-1.29) for the second to fifth quintiles as compared with the first. The risk estimates were similar for α-tocopherol but nonsignificant for β- and γ-tocopherol combined and for γ-tocopherol. Adjustment for serum lipids strengthened the nonlinear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than nonusers (21.32 ± 9.04 vs. 17.72 ± 7.43 μg/mL; P < 0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. ©2013 AACR.

Prediagnostic serum tocopherol levels and the risk of Non-Hodgkin Lymphoma: The Multiethnic Cohort

PubMed Central

Morimoto, Yukiko; Ollberding, Nicholas J.; Cooney, Robert V.; Wilkens, Lynne R.; Franke, Adrian A.; Le Marchand, Loïc; Goodman, Marc T.; Hernandez, Brenda Y.; Kolonel, Laurence N.; Maskarinec, Gertraud

2013-01-01

Background Compromised immunity and chronic inflammation are thought to contribute to the development of non-Hodgkin lymphoma (NHL). Because tocopherols protect cells through antioxidant mechanisms, they may play a role in NHL etiology. Methods This nested case-control study within the Multiethnic Cohort examined the association of prediagnostic serum tocopherols levels measured in 271 NHL cases and 538 matched controls by high pressure liquid chromatography/photodiode-array detection with NHL risk. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). Results We observed U-shaped associations with NHL for total and α-tocopherols (Ptrend<0.01 for polynomial terms [3 df]). The ORs (95% CI) for total tocopherols, which consisted primarily of α-tocopherol, were 0.41 (0.25–0.68), 0.52 (0.32–0.85), 0.39 (0.23–0.65), and 0.78 (0.47–1.29) for the 2nd-5th quintiles as compared to the 1st. The risk estimates were similar for α-tocopherol but non-significant for β- and γ-tocopherol combined and for δ-tocopherol. Adjustment for serum lipids strengthened the non-linear associations for total and α-tocopherols. Serum total tocopherol levels were higher for vitamin E supplement users at cohort entry than non-users (21.32±9.04 vs 17.72±7.43 μg/mL; P <0.0001), but supplement use was not associated with NHL risk. No heterogeneity in risk estimates was detected by sex, ethnicity, vitamin E supplement use, or NHL subtype. Conclusions Circulating tocopherols, at levels likely reflecting adequate dietary intakes, may be protective against NHL, whereas higher intakes from supplementation may not be beneficial. Impact The association between serum tocopherol levels and NHL risk provides possible new insights into the etiology of NHL. PMID:24045922

Insufficient and excessive amounts of sleep increase the risk of premature death from cardiovascular and other diseases: the Multiethnic Cohort Study.

PubMed

Kim, Yeonju; Wilkens, Lynne R; Schembre, Susan M; Henderson, Brian E; Kolonel, Laurence N; Goodman, Marc T

2013-10-01

To explore an independent association between self-reported sleep duration and cause-specific mortality. Data were obtained from the Multiethnic Cohort Study conducted in Los Angeles and Hawaii. Among 61,936 men and 73,749 women with no history of cancer, heart attack or stroke, 19,335 deaths occurred during an average 12.9year follow-up. Shorter (≤5h/day) and longer (≥9h/day) sleepers of both sexes (vs. 7h/day) had an increased risk of all-cause and cardiovascular disease (CVD) mortality, but not of cancer mortality. Multivariable hazard ratios for CVD mortality were 1.13 (95% CI 1.00-1.28) for ≤5h/day and 1.22 (95% CI 1.09-1.35) for ≥9h/day among men; and 1.20 (95% CI 1.05-1.36) for ≤5h/day and 1.29 (95% CI 1.13-1.47) for ≥9h/day among women. This risk pattern was not heterogeneous across specific causes of CVD death among men (Phetero 0.53) or among women (Phetero 0.72). The U-shape association for all-cause and CVD mortality was observed in all five ethnic groups included in the study and by subgroups of age, smoking status, and body mass index. Insufficient or excessive amounts of sleep were associated with increased risk of mortality from CVD and other diseases in a multiethnic population. © 2013.

A plausibly causal functional lupus-associated risk variant in the STAT1-STAT4 locus.

PubMed

Patel, Zubin; Lu, Xiaoming; Miller, Daniel; Forney, Carmy R; Lee, Joshua; Lynch, Arthur; Schroeder, Connor; Parks, Lois; Magnusen, Albert F; Chen, Xiaoting; Pujato, Mario; Maddox, Avery; Zoller, Erin E; Namjou, Bahram; Brunner, Hermine I; Henrickson, Michael; Huggins, Jennifer L; Williams, Adrienne H; Ziegler, Julie T; Comeau, Mary E; Marion, Miranda C; Glenn, Stuart B; Adler, Adam; Shen, Nan; Nath, Swapan K; Stevens, Anne M; Freedman, Barry I; Pons-Estel, Bernardo A; Tsao, Betty P; Jacob, Chaim O; Kamen, Diane L; Brown, Elizabeth E; Gilkeson, Gary S; Alarcón, Graciela S; Martin, Javier; Reveille, John D; Anaya, Juan-Manuel; James, Judith A; Sivils, Kathy L; Criswell, Lindsey A; Vilá, Luis M; Petri, Michelle; Scofield, R Hal; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Bang, So-Young; Lee, Hye-Soon; Bae, Sang-Cheol; Boackle, Susan A; Cunninghame Graham, Deborah; Vyse, Timothy J; Merrill, Joan T; Niewold, Timothy B; Ainsworth, Hannah C; Silverman, Earl D; Weisman, Michael H; Wallace, Daniel J; Raj, Prithvi; Guthridge, Joel M; Gaffney, Patrick M; Kelly, Jennifer A; Alarcón-Riquelme, Marta E; Langefeld, Carl D; Wakeland, Edward K; Kaufman, Kenneth M; Weirauch, Matthew T; Harley, John B; Kottyan, Leah C

2018-04-18

Systemic Lupus Erythematosus (SLE or lupus) (OMIM: 152700) is a chronic autoimmune disease with debilitating inflammation that affects multiple organ systems. The STAT1-STAT4 locus is one of the first and most highly-replicated genetic loci associated with lupus risk. We performed a fine-mapping study to identify plausible causal variants within the STAT1-STAT4 locus associated with increased lupus disease risk. Using complementary frequentist and Bayesian approaches in trans-ancestral Discovery and Replication cohorts, we found one variant whose association with lupus risk is supported across ancestries in both the Discovery and Replication cohorts: rs11889341. In B cell lines from patients with lupus and healthy controls, the lupus risk allele of rs11889341 was associated with increased STAT1 expression. We demonstrated that the transcription factor HMGA1, a member of the HMG transcription factor family with an AT-hook DNA-binding domain, has enriched binding to the risk allele compared to the non-risk allele of rs11889341. We identified a genotype-dependent repressive element in the DNA within the intron of STAT4 surrounding rs11889341. Consistent with expression quantitative trait locus (eQTL) analysis, the lupus risk allele of rs11889341 decreased the activity of this putative repressor. Altogether, we present a plausible molecular mechanism for increased lupus risk at the STAT1-STAT4 locus in which the risk allele of rs11889341, the most probable causal variant, leads to elevated STAT1 expression in B cells due to decreased repressor activity mediated by increased binding of HMGA1.

Revised Framingham Stroke Risk Score, Nontraditional Risk Markers, and Incident Stroke in a Multiethnic Cohort.

PubMed

Flueckiger, Peter; Longstreth, Will; Herrington, David; Yeboah, Joseph

2018-02-01

Limited data exist on the performance of the revised Framingham Stroke Risk Score (R-FSRS) and the R-FSRS in conjunction with nontraditional risk markers. We compared the R-FSRS, original FSRS, and the Pooled Cohort Equation for stroke prediction and assessed the improvement in discrimination by nontraditional risk markers. Six thousand seven hundred twelve of 6814 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) were included. Cox proportional hazard, area under the curve, net reclassification improvement, and integrated discrimination increment analysis were used to assess and compare each stroke prediction risk score. Stroke was defined as fatal/nonfatal strokes (hemorrhagic or ischemic). After mean follow-up of 10.7 years, 231 of 6712 (3.4%) strokes were adjudicated (2.7% ischemic strokes). Mean stroke risks using the R-FSRS, original FSRS, and Pooled Cohort Equation were 4.7%, 5.9%, and 13.5%. The R-FSRS had the best calibration (Hosmer-Lemeshow goodness-of-fit, χ 2 =6.55; P =0.59). All risk scores were predictive of incident stroke. C statistics of R-FSRS (0.716) was similar to Pooled Cohort Equation (0.716), but significantly higher than the original FSRS (0.653; P =0.01 for comparison with R-FSRS). Adding nontraditional risk markers individually to the R-FSRS did not improve discrimination of the R-FSRS in the area under the curve analysis, but did improve category-less net reclassification improvement and integrated discrimination increment for incident stroke. The addition of coronary artery calcium to R-FSRS produced the highest category-less net reclassification improvement (0.36) and integrated discrimination increment (0.0027). Similar results were obtained when ischemic strokes were used as the outcome. The R-FSRS downgraded stroke risk but had better calibration and discriminative ability for incident stroke compared with the original FSRS. Nontraditional risk markers modestly improved the discriminative ability of the R-FSRS, with

Diagnosing Lupus

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... Lupus.org Sign Up for Our Newsletter Donate Diagnosing Lupus Learn about lab tests, lupus symptoms, and how ... doctor's appointment article Reducing time to diagnosis blog Diagnosing lupus Getting a lupus diagnosis is challenging. Here’s what ...

Risk stratification of patients with familial hypercholesterolemia in a multi-ethnic cohort

PubMed Central

2014-01-01

Background Heterozygous Familial hypercholesterolemia (FH) is a common autosomal dominant disorder resulting in in very high blood cholesterol levels and premature cardiovascular disease (CVD). However, there is a wide variation in the occurrence of CVD in these patients. The aim of this study is to determine risk factors that are responsible for the variability of CVD events in FH patients. Methods This is a retrospective analysis of a large multiethnic cohort of patients with definite FH attending the Healthy Heart Prevention Clinic in Vancouver, Canada. Cox proportional hazard regression analysis was used to assess the association of the risk factors to the hard cardiovascular outcomes. Results 409 patients were identified as having “definite” FH, according to the Dutch Lipid Clinic Network Criteria (DLCNC), with 111 (27%) having evidence of CVD. Male sex, family history of premature CVD, diabetes mellitus, low high density lipoprotein cholesterol (HDL-C) and high lipoprotein (a) (Lp (a)) were significant, independent risk factors for CVD. In men, family history, diabetes and low levels of HDL-C were significant risk factors while in women smoking, diabetes mellitus and high Lp (a) were significant risk factors for CVD. There were no significant differences in risk factors between ethnicities. Conclusion In conclusion, men and women differ in the impact of the risk factors on the presence of CVD with family history of CVD and low HDL-C being a significant factor in men while smoking and increased Lp (a) were significant factors in women. Diabetes was a significant factor in both men and women. PMID:24712315

Renal transplantation in lupus nephritis: a Brazilian cohort.

PubMed

Oliveira, C S; d Oliveira, I; Bacchiega, A B S; Klumb, E M; Albuquerque, E M M; Souza, E; Suassuna, J H S; Ribeiro, F M

2012-04-01

To determine the epidemiological profile and outcome of patients with lupus nephritis (LN) undergoing renal transplantation. The archival records of 50 patients with LN and end-stage renal disease (ESRD) treated by kidney transplantation from March 1992 to December 2010 were reviewed. All patients met the American College of Rheumatology criteria for systemic lupus erythematosus (SLE). Fourteen patients were included in the study. The majority were women (85.7%) and non-Caucasian (85.7%); the mean age at diagnosis of SLE and LN was 24 ± 8 and 25 ± 8 years, respectively. Renal biopsy was performed in 12 patients, with 75% of them showing proliferative lesions (class III and IV according to the World Health Organization and International Society of Nephrology/Renal Pathology Society classification). Thirteen patients (93%) underwent intermittent hemodialysis or peritoneal dialysis before transplantation. The median time between the start of dialysis and transplantation was 30 months (range 3-103 months); 67% of the procedures involved deceased donors and 33% involved living-related donors. The graft survival rates were 93.3%, 90.9%, and 85.7% at 1, 5 and 10 years, respectively. Post-transplant immunosuppressive agents were mycophenolate mofetil (84%), azathioprine (17%), tacrolimus (25%), sirolimus (58%) and cyclosporine (8%). Eight episodes of acute rejection were noted in six patients. There was a graft loss due to renal vein thrombosis in the one patient with secondary antiphospholipid syndrome. The mean SLICC by the time of kidney transplantation was 5 ± 2. In total, 13 patients (92.8%) developed at least one infectious event during the follow-up, with one dying in the immediate post-transplant period because of sepsis. Two patients (14%) had a lupus flare. There was no clinical or histological evidence of LN recurrence. LN is the major cause of morbidity in SLE, with progression to ESRD in 10-22% of cases. Despite concerns about LN recurrence

Relationship between damage clustering and mortality in systemic lupus erythematosus in early and late stages of the disease: cluster analyses in a large cohort from the Spanish Society of Rheumatology Lupus Registry.

PubMed

Pego-Reigosa, José María; Lois-Iglesias, Ana; Rúa-Figueroa, Íñigo; Galindo, María; Calvo-Alén, Jaime; de Uña-Álvarez, Jacobo; Balboa-Barreiro, Vanessa; Ibáñez Ruan, Jesús; Olivé, Alejandro; Rodríguez-Gómez, Manuel; Fernández Nebro, Antonio; Andrés, Mariano; Erausquin, Celia; Tomero, Eva; Horcada Rubio, Loreto; Uriarte Isacelaya, Esther; Freire, Mercedes; Montilla, Carlos; Sánchez-Atrio, Ana I; Santos-Soler, Gregorio; Zea, Antonio; Díez, Elvira; Narváez, Javier; Blanco-Alonso, Ricardo; Silva-Fernández, Lucía; Ruiz-Lucea, María Esther; Fernández-Castro, Mónica; Hernández-Beriain, José Ángel; Gantes-Mora, Marian; Hernández-Cruz, Blanca; Pérez-Venegas, José; Pecondón-Español, Ángela; Marras Fernández-Cid, Carlos; Ibáñez-Barcelo, Mónica; Bonilla, Gema; Torrente-Segarra, Vicenç; Castellví, Iván; Alegre, Juan José; Calvet, Joan; Marenco de la Fuente, José Luis; Raya, Enrique; Vázquez-Rodríguez, Tomás Ramón; Quevedo-Vila, Víctor; Muñoz-Fernández, Santiago; Otón, Teresa; Rahman, Anisur; López-Longo, Francisco Javier

2016-07-01

To identify patterns (clusters) of damage manifestations within a large cohort of SLE patients and evaluate the potential association of these clusters with a higher risk of mortality. This is a multicentre, descriptive, cross-sectional study of a cohort of 3656 SLE patients from the Spanish Society of Rheumatology Lupus Registry. Organ damage was ascertained using the Systemic Lupus International Collaborating Clinics Damage Index. Using cluster analysis, groups of patients with similar patterns of damage manifestations were identified. Then, overall clusters were compared as well as the subgroup of patients within every cluster with disease duration shorter than 5 years. Three damage clusters were identified. Cluster 1 (80.6% of patients) presented a lower amount of individuals with damage (23.2 vs 100% in clusters 2 and 3, P < 0.001). Cluster 2 (11.4% of patients) was characterized by musculoskeletal damage in all patients. Cluster 3 (8.0% of patients) was the only group with cardiovascular damage, and this was present in all patients. The overall mortality rate of patients in clusters 2 and 3 was higher than that in cluster 1 (P < 0.001 for both comparisons) and in patients with disease duration shorter than 5 years as well. In a large cohort of SLE patients, cardiovascular and musculoskeletal damage manifestations were the two dominant forms of damage to sort patients into clinically meaningful clusters. Both in early and late stages of the disease, there was a significant association of these clusters with an increased risk of mortality. Physicians should pay special attention to the early prevention of damage in these two systems. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early Menopause Predicts Future Coronary Heart Disease and Stroke: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Wellons, Melissa; Ouyang, Pamela; Schreiner, Pamela J; Herrington, David M; Vaidya, Dhananjay

2012-01-01

Objective Cardiovascular disease is the number one killer of women. Identifying women at risk of cardiovascular disease has tremendous public health importance. Early menopause is associated with increased cardiovascular disease events in some predominantly white populations, but not consistently. Our objective was to determine if a self-reported early menopause (menopause at an age <46) identifies women as at risk for future coronary heart disease or stroke. Methods The study population came from the Multi-Ethnic Study of Atherosclerosis, a longitudinal, ethnically diverse cohort study of US men and women aged 45 to 84 years enrolled in 2000–2002 and followed up until 2008. The association between a personal history of early menopause (either natural menopause or surgical removal of ovaries at an age <46) and future coronary heart disease and stroke was assessed in 2509 women (ages 45–84, 987 White, 331 Chinese, 641 Black, 550 Hispanic) from the Multi-Ethnic Study Atherosclerosis, who were free of cardiovascular disease at baseline. Results 693/2509 (28%) of women reported either surgical or natural early menopause. In survival curves, women with early menopause had worse coronary heart disease and stroke-free survival (log rank p=<0.008 and 0.0158). In models adjusted for age, race/ethnicity, Multi-Ethnic Study Atherosclerosis site and traditional cardiovascular disease risk factors, this risk for coronary heart disease and stroke remained (HR 2.08, 95% CI 1.17, 3.70 and 2.19, 95% CI 1.11, 4.32, respectively). Conclusions Early menopause is positively associated with coronary heart disease and stroke in a multiethnic cohort, independent of traditional cardiovascular disease risk factors. PMID:22692332

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort.

PubMed

Pons-Estel, Guillermo J; González, Luis A; Zhang, Jie; Burgos, Paula I; Reveille, John D; Vilá, Luis M; Alarcón, Graciela S

2009-07-01

To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged >or=16 years, disease duration

Prevalence of chronic liver disease and cirrhosis by underlying cause in understudied ethnic groups: The multiethnic cohort.

PubMed

Setiawan, Veronica Wendy; Stram, Daniel O; Porcel, Jacqueline; Lu, Shelly C; Le Marchand, Loïc; Noureddin, Mazen

2016-12-01

Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n = 106,458). We used International Classification of Diseases Ninth Revision codes, body mass index, history of diabetes mellitus, and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos, and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NAFLD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. Alcoholic liver disease was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%). We showed racial/ethnic variations in the prevalence of CLD and cirrhosis by underlying etiology; NAFLD was the most common cause of CLD and cirrhosis in the entire cohort, and the high prevalence of NAFLD among Japanese Americans and Native Hawaiians is a novel finding, warranting further studies to elucidate the causes. (Hepatology 2016;64:1969-1977). © 2016 by the American Association for the Study of Liver Diseases.

Lupus - resources

MedlinePlus

Resources - lupus ... The following organizations are good resources for information on systemic lupus erythematosus : Genetics Home Reference -- ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus Lupus Foundation of America -- ...

Lupus

MedlinePlus

... and brain. There are several kinds of lupus Systemic lupus erythematosus (SLE) is the most common type. ... medicine can treat lupus. Some alternative or complementary approaches may help you cope or reduce some of ...

Prospective validation of a novel renal activity index of lupus nephritis.

PubMed

Gulati, G; Bennett, M R; Abulaban, K; Song, H; Zhang, X; Ma, Q; Brodsky, S V; Nadasdy, T; Haffner, C; Wiley, K; Ardoin, S P; Devarajan, P; Ying, J; Rovin, B H; Brunner, H I

2017-08-01

Objectives The renal activity index for lupus (RAIL) score was developed in children with lupus nephritis as a weighted sum of six urine biomarkers (UBMs) (neutrophil gelatinase-associated lipocalin, monocyte chemotactic protein 1, ceruloplasmin, adiponectin, hemopexin and kidney injury molecule 1) measured in a random urine sample. We aimed at prospectively validating the RAIL in adults with lupus nephritis. Methods Urine from 79 adults was collected at the time of kidney biopsy to assay the RAIL UBMs. Using receiver operating characteristic curve analysis, we evaluated the accuracy of the RAIL to discriminate high lupus nephritis activity status (National Institutes of Health activity index (NIH-AI) score >10), from low/moderate lupus nephritis activity status (NIH-AI score ≤10). Results In this mixed racial cohort, high lupus nephritis activity was present in 15 patients (19%), and 71% had proliferative lupus nephritis. Use of the identical RAIL algorithm developed in children resulted in only fair prediction of lupus nephritis activity status of adults (area under the receiver operating characteristic curve (AUC) 0.62). Alternative weightings of the six RAIL UBMs as suggested by logistic regression yielded excellent accuracy to predict lupus nephritis activity status (AUC 0.88). Accuracy of the model did not improve with adjustment of the UBMs for urine creatinine or albumin, and was little influenced by concurrent kidney damage. Conclusions The RAIL UBMs provide excellent prediction of lupus nephritis activity in adults. Age adaption of the RAIL is warranted to optimize its discriminative validity to predict high lupus nephritis activity status non-invasively.

Voice of the Voiceless? Multiethnic Student Voices in Critical Approaches to Race, Pedagogy, Literacy and Agency

ERIC Educational Resources Information Center

Chang, Benji

2013-01-01

In this article, the author utilizes critical and sociocultural approaches to race, language and culture to examine the intersectional experiences of a multiethnic and "mixed race" cohort of students in an inner-city, working-class neighborhood between their elementary and high school years. This article examines the students'…

Associations of key diet-quality indexes with mortality in the Multiethnic Cohort: the Dietary Patterns Methods Project.

PubMed

Harmon, Brook E; Boushey, Carol J; Shvetsov, Yurii B; Ettienne, Reynolette; Reedy, Jill; Wilkens, Lynne R; Le Marchand, Loic; Henderson, Brian E; Kolonel, Laurence N

2015-03-01

Healthy dietary patterns have been linked positively with health and longevity. However, prospective studies in diverse populations in the United States addressing dietary patterns and mortality are limited. We assessed the ability of the following 4 diet-quality indexes [the Healthy Eating Index-2010 (HEI-2010), the Alternative HEI-2010 (AHEI-2010), the alternate Mediterranean diet score (aMED), and the Dietary Approaches to Stop Hypertension (DASH)] to predict the reduction in risk of mortality from all causes, cardiovascular disease (CVD), and cancer. White, African American, Native Hawaiian, Japanese American, and Latino adults (n = 215,782) from the Multiethnic Cohort completed a quantitative food-frequency questionnaire. Scores for each dietary index were computed and divided into quintiles for men and women. Mortality was documented over 13-18 y of follow-up. HRs and 95% CIs were computed by using adjusted Cox models. High HEI-2010, AHEI-2010, aMED, and DASH scores were all inversely associated with risk of mortality from all causes, CVD, and cancer in both men and women (P-trend < 0.0001 for all models). For men, the HEI-2010 was consistently associated with a reduction in risk of mortality for all causes (HR: 0.75; 95% CI: 0.71, 0.79), CVD (HR: 0.74; 95% CI: 0.69, 0.81), and cancer (HR: 0.76; 95% CI: 0.70, 0.83) when lowest and highest quintiles were compared. In women, the AHEI and aMED showed large reductions for all-cause mortality (HR: 0.78; 95% CI: 0.74, 0.82), the AHEI showed large reductions for CVD (HR: 0.76; 95% CI: 0.69, 0.83), and the aMED showed large reductions for cancer (HR: 0.84; 95% CI: 0.76, 0. 92). These results, in a US multiethnic population, suggest that consuming a dietary pattern that achieves a high diet-quality index score is associated with lower risk of mortality from all causes, CVD, and cancer in adult men and women. © 2015 American Society for Nutrition.

Genetic Basis of Autoantibody Positive and Negative Rheumatoid Arthritis Risk in a Multi-ethnic Cohort Derived from Electronic Health Records

PubMed Central

Kurreeman, Fina; Liao, Katherine; Chibnik, Lori; Hickey, Brendan; Stahl, Eli; Gainer, Vivian; Li, Gang; Bry, Lynn; Mahan, Scott; Ardlie, Kristin; Thomson, Brian; Szolovits, Peter; Churchill, Susanne; Murphy, Shawn N.; Cai, Tianxi; Raychaudhuri, Soumya; Kohane, Isaac; Karlson, Elizabeth; Plenge, Robert M.

2011-01-01

Discovering and following up on genetic associations with complex phenotypes require large patient cohorts. This is particularly true for patient cohorts of diverse ancestry and clinically relevant subsets of disease. The ability to mine the electronic health records (EHRs) of patients followed as part of routine clinical care provides a potential opportunity to efficiently identify affected cases and unaffected controls for appropriate-sized genetic studies. Here, we demonstrate proof-of-concept that it is possible to use EHR data linked with biospecimens to establish a multi-ethnic case-control cohort for genetic research of a complex disease, rheumatoid arthritis (RA). In 1,515 EHR-derived RA cases and 1,480 controls matched for both genetic ancestry and disease-specific autoantibodies (anti-citrullinated protein antibodies [ACPA]), we demonstrate that the odds ratios and aggregate genetic risk score (GRS) of known RA risk alleles measured in individuals of European ancestry within our EHR cohort are nearly identical to those derived from a genome-wide association study (GWAS) of 5,539 autoantibody-positive RA cases and 20,169 controls. We extend this approach to other ethnic groups and identify a large overlap in the GRS among individuals of European, African, East Asian, and Hispanic ancestry. We also demonstrate that the distribution of a GRS based on 28 non-HLA risk alleles in ACPA+ cases partially overlaps with ACPA- subgroup of RA cases. Our study demonstrates that the genetic basis of rheumatoid arthritis risk is similar among cases of diverse ancestry divided into subsets based on ACPA status and emphasizes the utility of linking EHR clinical data with biospecimens for genetic studies. PMID:21211616

Body Size, Adult BMI Gain and Endometrial Cancer Risk: The Multiethnic Cohort

PubMed Central

Park, Sungshim Lani; Goodman, Marc T.; Zhang, Zuo-Feng; Kolonel, Laurence N.; Henderson, Brian E.; Setiawan, Veronica Wendy

2009-01-01

The effect of body size and change in BMI on endometrial cancer risk across different racial/ethnic groups has not been studied. We examined the association between body size and endometrial cancer risk and potential effect modification of other risk factors among 50,376 women in the Multiethnic Cohort Study. During 10.3 years of follow-up, 463 endometrial cancer cases were identified. Epidemiologic data were collected from the baseline questionnaire. “BMI change” was defined as the percentage of body mass index change from age 21 to the time of recruitment. Women who were heavier at age 21 or at baseline (weight ≥ 53.5kg or ≥ 63.9 kg, respectively) had an increased endometrial cancer risk compared to the lowest quartile of weight during the respective periods. BMI gain ≥ 35% had a RR of 4.12 (95% CI: 2.69, 6.30) compared to the reference group (−5% ≤ BMI change <+5%). Women who averaged an annual BMI gain ≥ 1% had a >3.20-fold (95% CI: 2.37, 4.33) increased risk compared to women who maintained a stable adult BMI (−0.25 to <+0.25%). The highest risk associated with BMI gain was observed among nulliparous women and postmenopausal women who never used hormone therapy. While African Americans and Whites showed an increase in risk after ≥ 35% BMI gain, Japanese Americans showed an increase in risk with much smaller gain (≥ 5%). In conclusion, adult obesity and increase in adiposity are risk factors for endometrial cancer; and the risk associated with these factors may vary across racial/ethnic groups. PMID:19585578

Predictors of cardiovascular damage in patients with systemic lupus erythematosus: data from LUMINA (LXVIII), a multiethnic US cohort

PubMed Central

Pons-Estel, Guillermo J.; González, Luis A.; Zhang, Jie; Burgos, Paula I.; Reveille, John D.; Vilá, Luis M.

2009-01-01

Objective. To determine the features predictive of atherosclerotic cardiovascular damage in patients with SLE. Methods. SLE LUMINA (LUpus in MInorities: NAture vs nurture) patients (n = 637), aged ⩾16 years, disease duration ⩽5 years at baseline (T0), of African–American, Hispanic and Caucasian ethnicity were studied. Atherosclerotic cardiovascular damage was defined by the following items of the SLICC Damage Index (SDI) cardiovascular domain: angina or coronary artery by pass surgery, myocardial infarction and/or congestive heart failure; factors associated with its occurrence were examined by univariable and multivariable regression analyses. Results. Forty-three (6.8%) of 637 patients developed cardiovascular damage over a mean ± s.d. total disease duration of 6.6 ± 3.6 years. Nearly 90% of the patients were women with a mean ± s.d. age of 36.5 (12.6) years; all ethnic groups were represented. By multivariable analyses, after adjusting for the cardiovascular manifestations present, age [odds ratio (OR) = 1.06; 95% CI 1.03, 1.09], male gender (OR = 3.57; 95% CI 1.35, 9.09) SDI at baseline (OR = 1.28; 95% CI 1.09, 1.50) and CRP levels [highest tertile (OR = 2.63; 95% CI 1.17, 5.91)] were associated with the occurrence of cardiovascular damage, whereas the number of years of education was negatively associated with such outcome (OR = 0.85; 95% CI 0.74, 0.94). Conclusions. Our data suggest that atherosclerotic cardiovascular damage in SLE is multifactorial; traditional (age, gender) and disease-related factors (CRP levels, SDI at baseline) appear to be important contributors to such an occurrence. Tight control of the inflammatory process must be achieved to prevent it. PMID:19454606

Serious infections among adult Medicaid beneficiaries with systemic lupus erythematosus and lupus nephritis.

PubMed

Feldman, Candace H; Hiraki, Linda T; Winkelmayer, Wolfgang C; Marty, Francisco M; Franklin, Jessica M; Kim, Seoyoung C; Costenbader, Karen H

2015-06-01

To examine the epidemiology of serious infections, a significant cause of morbidity and mortality in systemic lupus erythematosus (SLE), in a nationwide cohort of SLE and lupus nephritis (LN) patients. Using the Medicaid Analytic eXtract database for the years 2000-2006, we identified patients ages 18-64 years who had SLE and the subset who had LN. We ascertained cases of serious hospitalized infections using validated algorithms, and we determined 30-day mortality rates. Poisson regression was used to calculate infection incidence rates and multivariable Cox proportional hazards models were used to calculate hazard ratios (HRs) for the first infection, adjusted for sociodemographic variables, medication use, and an SLE-specific risk adjustment index. We identified 33,565 patients with SLE, 7,113 of whom had LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection incidence rate per 100 person-years was 10.8 in the SLE cohort and 23.9 in the LN subcohort. In adjusted models for the SLE cohort, we observed increased risks of infection in men as compared to women (HR 1.33 [95% confidence interval (95% CI) 1.20-1.47]), in blacks as compared to whites (HR 1.14 [95% CI 1.06-1.21]), and in users of glucocorticoids (HR 1.51 [95% CI 1.43-1.61]) and immunosuppressive drugs (HR 1.11 [95% CI 1.03-1.20]) as compared to never users. Hydroxychloroquine users had a reduced risk of infection as compared to never users (HR 0.73 [95% CI 0.68-0.77]). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in the SLE cohort and 38.6 in the LN subcohort. In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths, particularly among those with LN. © 2015, American College of Rheumatology.

Incidence of cancer in a cohort of Spanish patients with systemic lupus erythematosus.

PubMed

Hidalgo-Conde, Ana; de Haro Liger, Manuel; Abarca-Costalago, Manuel; Álvarez Pérez, Martina; Valdivielso-Felices, Pedro; González-Santos, Pedro; Fernández-Nebro, Antonio

2013-01-01

To determine the incidence and prevalence of cancer in a cohort of patients with systemic lupus erythematosus (SLE) and identify associated risk factors. The study comprised a dynamic cohort of SLE patients (November 1989 to December 2006) at a tertiary referral centre. An adjusted external control from the hospital tumour registry was used. The study included 175 SLE patients (90% women), with a mean time at risk of 1370.5 patient-years. Fourteen women (8%) died, mainly from cardiovascular events. No patient died due to malignancy. We found 35 tumours in 28 patients, 25 of them after the diagnosis of SLE, of which 5 were malignant. The rate of benign tumours was 14.6/1000 patient-years (95% CI, 8.9-22.5) and of malignant tumours 3.6/1000 patient-years (95% CI, 1.5-8.8), with a crude incidence odds ratio for malignant tumours of 3.5 (95% CI, 1.5-7.9). However, this significance was lost after standardizing the rates. Concerning associated risk factors, differences were found in the mean erythrocyte sedimentation rate [HR 1.4 (1.1-1.7)], and the presence of thrombosis [HR 6.9 (1.49-41.2)], especially arterial thrombosis. We found a crude incidence rate of cancer that was almost four times greater in our SLE patients as compared with the expected rate in the hospital area of western Malaga. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Domains of health-related quality of life important and relevant to multiethnic English-speaking Asian systemic lupus erythematosus patients: a focus group study.

PubMed

Ow, Yen Ling Mandy; Thumboo, Julian; Cella, David; Cheung, Yin Bun; Yong Fong, Kok; Wee, Hwee Lin

2011-06-01

To identify health-related quality of life (HRQOL) domains of importance to multiethnic Asian systemic lupus erythematosus (SLE) patients, to identify content gaps in existing SLE-specific HRQOL measures, and to determine whether the Patient-Reported Outcomes Measurement Information System (PROMIS) item banks could serve as a core set of questions for HRQOL assessment among SLE patients. English-speaking patients with physician-diagnosed SLE from a specialist clinic in a tertiary care hospital in Singapore and a patient support group were recruited. Thematic analysis was performed to distill themes from transcripts through open coding by 2 independent coders and axial coding for refinement of categories. Items from 3 existing SLE-specific measures and PROMIS Version 1.0 Item Banks were compared with identified subthemes. Twenty-seven female and 2 male participants (21 Chinese, 4 Malay, 3 Indian, 1 other) ages 23-62 years participated in 6 focus groups and 2 individual interviews, respectively. Twenty-one domains and 92 subthemes were identified. Domains of family, relationships, stigma and discrimination, and freedom were unaddressed by existing SLE-specific measures. Forty subthemes from 14 domains were addressed by the PROMIS Version 1.0 Item Banks (Physical Function, Pain, Fatigue, Sleep Disturbance, Sleep-Related Impairment, Anger, Anxiety, and Depression banks). Family and stigma and discrimination (identified as content gaps) may be accentuated in the Asian sociocultural context. PROMIS item banks have tremendous potential to serve as a core set of items for HRQOL assessment in SLE patients. Additional items may be written to fill the gaps in existing PROMIS item banks. Copyright © 2011 by the American College of Rheumatology.

Low Prevalence of CHEK2 Gene Mutations in Multiethnic Cohorts of Breast Cancer Patients in Malaysia

PubMed Central

Mohamad, Suriati; Isa, Nurismah Md; Muhammad, Rohaizak; Emran, Nor Aina; Kitan, Nor Mayah; Kang, Peter; Kang, In Nee; Taib, Nur Aishah Mohd; Teo, Soo Hwang; Akmal, Sharifah Noor

2015-01-01

CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population. PMID:25629968

Low prevalence of CHEK2 gene mutations in multiethnic cohorts of breast cancer patients in Malaysia.

PubMed

Mohamad, Suriati; Isa, Nurismah Md; Muhammad, Rohaizak; Emran, Nor Aina; Kitan, Nor Mayah; Kang, Peter; Kang, In Nee; Taib, Nur Aishah Mohd; Teo, Soo Hwang; Akmal, Sharifah Noor

2015-01-01

CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.

Systemic Lupus Erythematosus with and without Anti-dsDNA Antibodies: Analysis from a Large Monocentric Cohort.

PubMed

Conti, Fabrizio; Ceccarelli, Fulvia; Perricone, Carlo; Massaro, Laura; Marocchi, Elisa; Miranda, Francesca; Spinelli, Francesca Romana; Truglia, Simona; Alessandri, Cristiano; Valesini, Guido

2015-01-01

The anti-dsDNA antibodies are a marker for Systemic Lupus Erythematosus (SLE) and 70-98% of patients test positive. We evaluated the demographic, clinical, laboratory, and therapeutical features of a monocentric SLE cohort according to the anti-dsDNA status. We identified three groups: anti-dsDNA + (persistent positivity); anti-dsDNA ± (initial positivity and subsequent negativity during disease course); anti-dsDNA - (persistent negativity). Disease activity was assessed by the European Consensus Lupus Activity Measurement (ECLAM). We evaluated 393 patients (anti-dsDNA +: 62.3%; anti-dsDNA ±: 13.3%; anti-dsDNA -: 24.4%). The renal involvement was significantly more frequent in anti-dsDNA + (30.2%), compared with anti-dsDNA ± and anti-dsDNA - (21.1% and 18.7%, resp.; P = 0.001). Serositis resulted significantly more frequent in anti-dsDNA - (82.3%) compared to anti-dsDNA + and anti-dsDNA ± (20.8% and 13.4%, resp.; P < 0.0001). The reduction of C4 serum levels was identified significantly more frequently in anti-dsDNA + and anti-dsDNA ± (40.0% and 44.2%, resp.) compared with anti-dsDNA - (21.8%, P = 0.005). We did not identify significant differences in the mean ECLAM values before and after modification of anti-dsDNA status (P = 0.7). Anti-dsDNA status influences the clinical and immunological features of SLE patients. Nonetheless, it does not appear to affect disease activity.

Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility

PubMed Central

Cook, James P; Morris, Andrew P

2016-01-01

Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 × 10−8) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry. PMID:27189021

Knowledge of gestational diabetes among a multi-ethnic cohort in Australia.

PubMed

Carolan, Mary; Steele, Cheryl; Margetts, Heather

2010-12-01

to explore knowledge about gestational diabetes (GDM) among a multi-ethnic sample of women who were receiving antenatal care in Melbourne, Australia. cross-sectional comparative survey. diabetes clinic located in a public hospital in Melbourne's Western suburbs. 143 pregnant women with GDM from Vietnamese, Indian, Filipino and Caucasian backgrounds. 200 questionnaires were distributed and 143 were returned (response rate 71.5%). There were statistically significant differences between ethnic groups in terms of educational level (p=0.001) and fluency in English (p=0.001). Educational levels, measured in completed years of schooling, were lowest among Vietnamese [mean 8.5 years, standard deviation (SD) 1.0], Filipino (mean 8.9 years, SD 1.5) and Caucasian [mean 10.2 years, SD 0.9] women. Indian women had a higher mean level of education (11.6 years, SD 0.9). Fluency in English was reported by 100% of Caucasian, Indian and Filipino women, but 53.3% of Vietnamese women required interpreter services. The women's answers varied with ethnicity and educational status. Vietnamese and Filipino women displayed the least knowledge about GDM and food values. Caucasian women also scored poorly on general knowledge about GDM. Indian women scored highest across all areas of interest. Vietnamese women had the poorest English skills and lowest educational levels, and were identified as the group at greatest risk of misunderstanding GDM. English language proficiency alone, however, was not associated with better comprehension of GDM in this study. Higher educational level was the only factor linked to increased comprehension. It is, therefore, important that new educational strategies are developed to address lower health literacy as well as cultural factors when caring for multi-ethnic populations with GDM. This approach may also serve to address lower levels of comprehension among Caucasian populations. Copyright © 2009. Published by Elsevier Ltd.

Meat consumption, heterocyclic amines and colorectal cancer risk: the Multiethnic Cohort Study.

PubMed

Ollberding, Nicholas J; Wilkens, Lynne R; Henderson, Brian E; Kolonel, Laurence N; Le Marchand, Loïc

2012-10-01

Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazard models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RR(Q5 vs. Q1) = 0.93 [0.83-1.05]), red meat (RR = 1.02 [0.91-1.16]) or processed meat intake (RR = 1.06 [0.94-1.19]) or for total (RR = 0.90 [0.76-1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect. Copyright © 2012 UICC.

Meat Consumption, Heterocyclic Amines, and Colorectal Cancer Risk: The Multiethnic Cohort Study

PubMed Central

Ollberding, Nicholas J.; Wilkens, Lynne R.; Henderson, Brian E.; Kolonel, Laurence N.; Le Marchand, Loïc

2012-01-01

Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red, or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up, and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazards models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RRQ5 vs Q1=0.93 [0.83–1.05]), red meat (RR =1.02 [0.91–1.16]), or processed meat intake (RR =1.06 [0.94–1.19]), or for total (RR =0.90 [0.76–1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect. PMID:22438055

People: Annotated Multiethnic Bibliography K-12.

ERIC Educational Resources Information Center

Gilmore, Dolores D., Comp.; Petrie, Kenneth, Comp.

This annotated bibliography has been compiled to assist personnel in the selection of multiethnic media for schools. The bibliography includes sections entitled "Asian Americans,""Jewish Americans,""Mexican Americans,""Native Americans,""Puerto Rican Americans,""Other Hyphenated Americans," and "All Americans (Multiethnic)." The entries for the…

Association between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Ethnic Study of Atherosclerosis

USDA-ARS?s Scientific Manuscript database

While animal studies found vitamin K treatment reduced vascular calcification, human data are limited. Using a case-cohort design, we determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-ethnic Study of Atherosclerosis. Serum phylloquinone (v...

Dietary Red and Processed Meat Intake and Markers of Adiposity and Inflammation: The Multiethnic Cohort Study.

PubMed

Chai, Weiwen; Morimoto, Yukiko; Cooney, Robert V; Franke, Adrian A; Shvetsov, Yurii B; Le Marchand, Loïc; Haiman, Christopher A; Kolonel, Laurence N; Goodman, Marc T; Maskarinec, Gertraud

2017-07-01

The potential influence of dietary factors on inflammation is important for cancer prevention. Utilizing data from control participants (312 men, 911 women) in 2 nested case-control studies of cancer within the Multiethnic Cohort, we examined the associations of red and processed meat intake with serum levels of leptin, adiponectin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 and the mediator effect of body mass index (BMI) on the above associations (if present). Multivariable linear models were applied to assess the association between red and processed meat intake at cohort entry and serum biomarker levels measured 9.1 years later after adjusting for covariates and to determine the mediator effect of BMI. Overall red and processed meat intake was positively associated with serum leptin levels in men (β = 0.180, p = 0.0004) and women (β = 0.167, p < 0.0001). In women, higher red and processed meat consumption was significantly associated with higher CRP (β = 0.069, p = 0.03) and lower adiponectin levels (β = -0.082, p = 0.005). In mediation analyses with red and processed meat intake and BMI as predictors, the associations of red and processed meat with biomarkers decreased substantially (as indicated by percentage change in effect: leptin in men, 13.4%; leptin in women, 13.7%; adiponectin in women, -4.7%; CRP in women, 7.4%) and were no longer significant (p > 0.05), whereas BMI remained significantly associated with serum leptin (men: β = 3.209, p < 0.0001; women: β = 2.891, p < 0.0001), adiponectin (women: β = -1.085, p < 0.0001), and CRP (women: β = 1.581, p < 0.0001). The current data suggest that the amount of excess body weight or the degree of adiposity may mediate the relations between dietary red and processed meat intake and serum biomarkers associated with obesity and inflammation.

Children & Teens (with Lupus)

MedlinePlus

... of America Search Query (required) Search Understanding Lupus Diagnosing Lupus Living with Lupus Research on Lupus View All ... article Medications for treating lupus in children article Diagnosing lupus in children article Types of health care providers ...

Outcomes of neuropsychiatric events in systemic lupus erythematosus based on clinical phenotypes; prospective data from the Leiden NP SLE cohort.

PubMed

Magro-Checa, C; Beaart-van de Voorde, L J J; Middelkoop, H A M; Dane, M L; van der Wee, N J; van Buchem, M A; Huizinga, T W J; Steup-Beekman, G M

2017-04-01

Objective The objective of this study was to assess whether clinical and patient's reported outcomes are associated with a different pathophysiological origin of neuropsychiatric events presenting in systemic lupus erythematosus. Methods A total of 232 neuropsychiatric events presenting in 131 systemic lupus erythematosus patients were included. Neuropsychiatric systemic lupus erythematosus diagnosis was established per event by multidisciplinary evaluation. All neuropsychiatric events were divided according to a suspected underlying pathophysiological process into one of the following: non-neuropsychiatric systemic lupus erythematosus related, inflammatory and ischaemic neuropsychiatric systemic lupus erythematosus. The clinical outcome of all neuropsychiatric events was determined by a physician-completed four-point Likert scale. Health-related quality of life was measured with the subscales of the patient-generated Short Form 36 (SF-36) health survey questionnaire. The change between scores at paired visits of all domain scores, mental component summary (SF-36 MCS) and physical component summary (SF-36 PCS) scores were retrospectively calculated and used as patient-reported outcome. The association among these outcomes and the different origin of neuropsychiatric events was obtained using multiple logistic regression analysis. Results The clinical status of 26.8% non-neuropsychiatric systemic lupus erythematosus events, 15.8% ischaemic neuropsychiatric systemic lupus erythematosus and 51.6% inflammatory neuropsychiatric systemic lupus erythematosus improved after re-assessment. Almost all SF-36 domains had a positive change at re-assessment in all groups independently of the origin of neuropsychiatric events. Neuropsychiatric systemic lupus erythematosus ( B = 0.502; p < 0.001) and especially inflammatory neuropsychiatric systemic lupus erythematosus ( B = 0.827; p < 0.001) had better clinical outcome, with change in disease activity being the

Acculturation is associated with left ventricular mass in a multiethnic sample: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Effoe, Valery S; Chen, Haiying; Moran, Andrew; Bertoni, Alain G; Bluemke, David A; Seeman, Teresa; Darwin, Christine; Watson, Karol E; Rodriguez, Carlos J

2015-12-03

Acculturation involves stress-related processes and health behavioral changes, which may have an effect on left ventricular (LV) mass, a risk factor for cardiovascular disease (CVD). We examined the relationship between acculturation and LV mass in a multiethnic cohort of White, African-American, Hispanic and Chinese subjects. Cardiac magnetic resonance assessment was available for 5004 men and women, free of clinical CVD at baseline. Left ventricular mass index was evaluated as LV mass indexed by body surface area. Acculturation was characterized based on language spoken at home, place of birth and length of stay in the United States (U.S.), and a summary acculturation score ranging from 0 = least acculturated to 5 = most acculturated. Mean LV mass index adjusted for traditional CVD risk factors was compared across acculturation levels. Unadjusted mean LV mass index was 78.0 ± 16.3 g/m(2). In adjusted analyses, speaking exclusively English at home compared to non-English language was associated with higher LV mass index (81.3 ± 0.4 g/m(2) vs 79.9 ± 0.5 g/m(2), p = 0.02). Among foreign-born participants, having lived in the U.S. for ≥ 20 years compared to < 10 years was associated with greater LV mass index (81.6 ± 0.7 g/m(2) vs 79.5 ± 1.1 g/m(2), p = 0.02). Compared to those with the lowest acculturation score, those with the highest score had greater LV mass index (78.9 ± 1.1 g/m(2) vs 81.1 ± 0.4 g/m(2), p = 0.002). There was heterogeneity in which measure of acculturation was associated with LV mass index across ethnic groups. Greater acculturation is associated with increased LV mass index in this multiethnic cohort. Acculturation may involve stress-related processes as well as behavioral changes with a negative effect on cardiovascular health.

Time-location patterns of a diverse population of older adults: the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air).

PubMed

Spalt, Elizabeth W; Curl, Cynthia L; Allen, Ryan W; Cohen, Martin; Adar, Sara D; Stukovsky, Karen H; Avol, Ed; Castro-Diehl, Cecilia; Nunn, Cathy; Mancera-Cuevas, Karen; Kaufman, Joel D

2016-06-01

The primary aim of this analysis was to present and describe questionnaire data characterizing time-location patterns of an older, multiethnic population from six American cities. We evaluated the consistency of results from repeated administration of this questionnaire and between this questionnaire and other questionnaires collected from participants of the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). Participants reported spending most of their time inside their homes (average: 121 h/week or 72%). More than 50% of the participants reported spending no time in several of the location options, including at home outdoors, at work/volunteer/school locations indoors or outdoors, or in "other" locations outdoors. We observed consistency between self-reported time-location patterns from repeated administration of the time-location questionnaire and compared with other survey instruments. Comparisons with national cohorts demonstrated the differences in time-location patterns in the MESA Air cohort due to differences in demographics, but the data showed similar trends in patterns by age, gender, season, and employment status. This study was the first to explicitly examine the time-location patterns in an older, multiethnic population and the first to add data on Chinese participants. These data can be used to inform future epidemiological research of MESA Air and other studies that include diverse populations.

Lupus Nephritis

MedlinePlus

... can be a sign of lupus nephritis. What tests do health care professionals use to diagnose lupus nephritis? Lupus nephritis ... and blood tests and a kidney biopsy. Urine Test Your health care professional uses a urine sample to look for ...

Lupus nephritis susceptibility loci in women with systemic lupus erythematosus.

PubMed

Chung, Sharon A; Brown, Elizabeth E; Williams, Adrienne H; Ramos, Paula S; Berthier, Celine C; Bhangale, Tushar; Alarcon-Riquelme, Marta E; Behrens, Timothy W; Criswell, Lindsey A; Graham, Deborah Cunninghame; Demirci, F Yesim; Edberg, Jeffrey C; Gaffney, Patrick M; Harley, John B; Jacob, Chaim O; Kamboh, M Ilyas; Kelly, Jennifer A; Manzi, Susan; Moser-Sivils, Kathy L; Russell, Laurie P; Petri, Michelle; Tsao, Betty P; Vyse, Tim J; Zidovetzki, Raphael; Kretzler, Matthias; Kimberly, Robert P; Freedman, Barry I; Graham, Robert R; Langefeld, Carl D

2014-12-01

Lupus nephritis is a manifestation of SLE resulting from glomerular immune complex deposition and inflammation. Lupus nephritis demonstrates familial aggregation and accounts for significant morbidity and mortality. We completed a meta-analysis of three genome-wide association studies of SLE to identify lupus nephritis-predisposing loci. Through genotyping and imputation, >1.6 million markers were assessed in 2000 unrelated women of European descent with SLE (588 patients with lupus nephritis and 1412 patients with lupus without nephritis). Tests of association were computed using logistic regression adjusting for population substructure. The strongest evidence for association was observed outside the MHC and included markers localized to 4q11-q13 (PDGFRA, GSX2; P=4.5×10(-7)), 16p12 (SLC5A11; P=5.1×10(-7)), 6p22 (ID4; P=7.4×10(-7)), and 8q24.12 (HAS2, SNTB1; P=1.1×10(-6)). Both HLA-DR2 and HLA-DR3, two well established lupus susceptibility loci, showed evidence of association with lupus nephritis (P=0.06 and P=3.7×10(-5), respectively). Within the class I region, rs9263871 (C6orf15-HCG22) had the strongest evidence of association with lupus nephritis independent of HLA-DR2 and HLA-DR3 (P=8.5×10(-6)). Consistent with a functional role in lupus nephritis, intra-renal mRNA levels of PDGFRA and associated pathway members showed significant enrichment in patients with lupus nephritis (n=32) compared with controls (n=15). Results from this large-scale genome-wide investigation of lupus nephritis provide evidence of multiple biologically relevant lupus nephritis susceptibility loci. Copyright © 2014 by the American Society of Nephrology.

Mild and moderate Mannose Binding Lectin deficiency are associated with systemic lupus erythematosus and lupus nephritis in Brazilian patients.

PubMed

Perazzio, Sandro Félix; Silva, Neusa Pereira da; Carneiro-Sampaio, Magda; Andrade, Luis Eduardo Coelho

2016-01-01

The potential association of mannose binding lectin (MBL) deficiency and systemic lupus erythematosus (SLE) has been investigated in several studies, but results have been mixed. One explanation for the conflicting results could be differences in ethnic background of study subjects. In this study we investigated the association of MBL deficiency and SLE in a large cohort of Brazilian SLE patients and controls. Serum MBL and Complement levels were determined for 286 Brazilian adult SLE patients and 301 healthy Brazilian adults as controls. MBL deficiency was classified as mild (<1000 and ≥500μg/L), moderate (<500 and ≥100μg/L) or severe (<100μg/L). SLE patients presented higher frequency of mild and moderate MBL deficiency compared to controls. SLE patients with MBL deficiency presented higher frequency of lupus nephritis compared to those without MBL deficiency. MBL deficiency was not associated with any other clinical manifestation, use of immunosuppressant therapy, disease activity, disease severity serum or Complement levels. This study shows that an association between MBL deficiency and SLE does exist in the Brazilian population. We also found an association between MBL deficiency and lupus nephritis. These findings support the hypothesis that MBL deficiency contributes to the development of SLE and lupus nephritis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Different Types of Lupus

MedlinePlus

... Twitter Facebook Pinterest Email Print Different types of lupus Lupus Foundation of America September 18, 2017 Resource ... lupus. Learn more about each type below. Systemic lupus erythematosus Systemic lupus is the most common form ...

Sleep Is Associated with the Metabolic Syndrome in a Multi-Ethnic Cohort of Midlife Women: The SWAN Sleep Study

PubMed Central

Hall, Martica H.; Okun, Michele L.; Sowers, MaryFran; Matthews, Karen A.; Kravitz, Howard M.; Hardin, Kimberly; Buysse, Daniel J.; Bromberger, Joyce T.; Owens, Jane F.; Karpov, Irina; Sanders, Mark H.

2012-01-01

syndrome in a multi-ethnic cohort of midlife women: the SWAN Sleep Study. SLEEP 2012;35(6):783-790. PMID:22654197

Oral candidiasis in systemic lupus erythematosus.

PubMed

Fangtham, M; Magder, L S; Petri, M A

2014-06-01

We assessed the frequency of oral candidiasis and the association between demographic variables, disease-related variables, corticosteroid treatment, other treatments and the occurrence of oral candidiasis in the Hopkins Lupus Cohort. In this large prospective cohort study of 2258 patients with systemic lupus erythematosus (SLE), demographic and clinical associates of oral candidiasis were estimated by univariate, multivariate and within-person regression models. There were 53,548 cohort visits. Oral candidiasis was diagnosed at 675 visits (1.25%) in 325 (14%) of the patients. In the multivariate analyses, oral candidiasis was associated with African-American ethnicity, SELENA-SLEDAI disease activity, high white blood cell count, a history of bacterial infection, prednisone use and immunosuppressive use. The urine protein by urine dip stick was higher in SLE patients with oral candidiasis. Considering only patients who had candidiasis at some visits in a 'within-person' analysis, candidiasis was more frequent in visits with higher SELENA-SLEDAI disease activity, high white blood cell count, proteinuria by urine dip stick, a history of bacterial infection and prednisone use. The use of hydroxychloroquine was associated with a lower risk of oral candidiasis, but was not statistically significant (p = 0.50) in the within-person analysis models. This study identified multiple risk factors for oral candidiasis in SLE. Inspection of the oral cavity for signs of oral candidiasis is recommended especially in SLE patients with active disease, proteinuria, high white blood cell count, taking prednisone, immunosuppressive drugs or antibiotics. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Intake of cocoa products and risk of type-2 diabetes: the multiethnic cohort.

PubMed

Maskarinec, Gertraud; Jacobs, Simone; Shvetsov, Yurii; Boushey, Carol J; Setiawan, Veronica W; Kolonel, Laurence N; Haiman, Christopher A; Le Marchand, Loïc

2018-05-24

As cocoa products may be protective against chronic disease due to their polyphenol content, the current study determined the association of chocolate consumption and flavanol intake with type-2 diabetes (T2D) incidence in the Multiethnic Cohort (MEC) Study. The analysis included 151,691 participants of Native Hawaiian, Japanese American, Latino, African American, and white ancestry with 8487 incident T2D cases after 7.8 ± 3.5 years of follow-up. T2D status was based on three self-reports and confirmed by at least one of three administrative data sources. Dietary intake was assessed using a validated quantitative food frequency questionnaire, and flavanols from cocoa products were estimated from self-reported consumption of chocolate candy and drinks. Cox hazard regression, adjusted for potential confounders was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI). For chocolate candy, both the highest vs. lowest (≥10 vs. <1 g/day) consumption (HR = 0.90; 95% CI, 0.83-0.97; p trend  = 0.01) and the frequency (≥4/week vs. <1/month) of intake (HR = 0.81; 95% CI, 0.72-0.91; p trend  = 0.0002) were inversely associated with T2D. The estimated flavanol intake from cocoa products (≥3 vs. <1 mg/day) also showed an inverse association with T2D risk (HR = 0.93; 95% CI, 0.88-0.99; p trend  = 0.02). Significant interaction terms indicated that the inverse relation was limited to Japanese Americans, normal-weight individuals, and to those without comorbidities. The current study confirms previous reports that participants with high intake of chocolate products and cocoa-derived flavanols experience a reduced risk of developing T2D even after controlling for sugar intake, diet quality, and other aspects of the diet.

Potassium Measures and Their Associations with Glucose and Diabetes Risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Chatterjee, Ranee; Zelnick, Leila; Mukamal, Kenneth J.; Nettleton, Jennifer A.; Kestenbaum, Bryan R.; Siscovick, David S.; Ix, Joachim H.; Tracy, Russell; Hoofnagle, Andrew N.; Svetkey, Laura P.; Edelman, David; de Boer, Ian H.

2016-01-01

Background Recent studies have found low-normal potassium (K) to be associated with increased diabetes risk. We sought to verify these associations in a multi-ethnic US cohort; and to determine if these associations extend to US Hispanics and Asian-Americans. Methods We analyzed data from Multi-Ethnic Study of Atherosclerosis (MESA) participants who were free-of-diabetes at baseline. We examined cross-sectional associations between measures of K—serum, dietary, and urine—with fasting glucose and HOMA-IR. We examined longitudinal associations between K and diabetes risk over 8 years. Findings In multivariable models, compared to those with higher serum K (≥4.5mmol/L), those with lower serum K (<4.0mmol/L) had significantly higher fasting glucose [1.3 mg/dL (95%CI 0.2, 2.4), P-value = 0.03]. Incident diabetes developed in 1281 of 5415 at-risk participants. In minimally-adjusted models, we found inverse associations between serum and dietary K and diabetes risk. Compared to those with higher serum K, those with lower serum K had an HR (95% CI) of incident diabetes of 1.23 (1.04, 1.47), P-value = 0.02. However, these associations were attenuated in fully-adjusted models. We found no significant interaction between potassium and ethnicity. Conclusions In this multi-ethnic cohort, we found a significant inverse association between serum K and fasting glucose but no significant association with longer-term diabetes risk. This inverse association between potassium and glucose must be studied further to understand the physiology and its potential impact on chronic health. PMID:27280455

Cigarette smoking and cutaneous damage in systemic lupus erythematosus.

PubMed

Turchin, Irina; Bernatsky, Sasha; Clarke, Ann E; St-Pierre, Yvan; Pineau, Christian A

2009-12-01

To evaluate the association between cigarette smoking and cutaneous damage in systemic lupus erythematosus (SLE). Our study was performed in SLE clinic registry cohort patients, all of whom fulfilled revised American College of Rheumatology criteria for SLE; patients are followed prospectively with annual assessments that include collection of demographic variables, smoking history, disease activity (SLE Disease Activity Index version 2000, SLEDAI-2K), medications, and damage scores (Systemic Lupus International Collaborating Clinics/ACR Damage Index). Cumulative cutaneous damage scores were used for the primary analyses. Logistic and logit regression models were performed to examine potential associations between current smoking and cutaneous damage, controlling for age, sex, race, lupus disease duration, antimalarial or immunosuppressant use, and anti-DNA and anti-SSA antibody status. Of our sample (N = 276), 92% were women and 73.7% were Caucasian; the mean age was 45.1 years, mean disease duration 13.5 years, and 17.5% were current smokers. In the regression analyses, current cigarette smoking was associated with total cutaneous damage (OR 2.73, 95% CI 1.10, 6.81) and with scarring (OR 4.70, 95 CI 1.04, 21.2). In additional analyses, current smoking was also associated with active lupus rash (OR 6.18, 95% CI 1.63, 23.3). Current cigarette smoking may be associated with cutaneous damage and active lupus rash in SLE, suggesting another reason to emphasize smoking cessation in patients with SLE.

Fostering a Pluralistic Society through Multi-Ethnic Education. Fastback 107.

ERIC Educational Resources Information Center

Garcia, Ricardo L.

The purpose of multiethnic education is to prepare all students to live harmoniously in a multiethnic society. Multiethnic education pursues these goals by reflecting ethnic diversity in the curriculum, dealing directly with ethnic group similarities and differences, and helping students understand their uniqueness in a pluralistic milieu.…

Pure cutaneous lupus erythematosus in a population of African descent in French Guiana: a retrospective population-based description.

PubMed

Deligny, C; Marie, D Sainte; Clyti, E; Arfi, S; Couppié, P

2012-11-01

The objective of this study was to examine the characteristics of cutaneous lupus erythematosus, excluding systemic lupus erythematosus (SLE), in patients of African descent. Indeed, since the description of subacute cutaneous lupus erythematosus (SCLE), which had been included in chronic cutaneous lupus erythematosus (CCLE), there has been no description of the disease in black patients. In 2000, we performed a retrospective epidemiological study by querying multiple sources to identify all patients with lupus in French Guiana--a part of France in South America having western living conditions, free healthcare and 157,000 inhabitants, most of whom are of African origin. We found 45 patients with pure cutaneous lupus, which included CCLE (mostly discoid), SCLE and bullous lupus. The disease characteristics of these patients exhibited few differences compared with those of the Caucasian patients cited in the literature. However, the age of onset for our patients of African descent was younger than that of Caucasian patients. In contrast to the race-related differences reported for SLE, we found no major differences in terms of demographic, clinical and biological presentation between this cohort of pure cutaneous lupus erythematosus patients of African origin and Caucasian patients with similar forms of lupus.

Impact of disease activity on health-related quality of life in systemic lupus erythematosus - a cross-sectional analysis of the Swiss Systemic Lupus Erythematosus Cohort Study (SSCS).

PubMed

Chaigne, Benjamin; Chizzolini, Carlo; Perneger, Thomas; Trendelenburg, Marten; Huynh-Do, Uyen; Dayer, Eric; Stoll, Thomas; von Kempis, Johannes; Ribi, Camillo

2017-03-28

To assess the impact of disease activity on health-related quality of life (HRQoL) in systemic lupus erythematosus (SLE). Cross-sectional study of patients included in the Swiss SLE Cohort Study between April 2007 and June 2014. HRQoL outcomes were based on the Medical Outcome Study Short Form 36 (SF-36). Disease activity was assessed by the SLE Disease Activity Index score with the Safety of Estrogens in SLE National Assessment modification (SELENA-SLEDAI) and by the physican's global assessment (PGA). Of the 252 patients included, 207 (82%) were women. Median [interquartile range (IQR)] age was 43 [32-57] years. SLE was active in 125 patients (49.6%). Median [IQR] mental component summary (MCS) in active vs inactive SLE was 40.0 [30.2-51.0] compared to 47.3 [39.2-52.8] (p < 0.01) and median [IQR] physical component summary (PCS) 43.7 [37.0-52.8] compared to 49.1 [38.4-55.6], respectively (p < 0.05). Increase in SELENA-SLEDAI or increase in PGA were negatively correlated with PCS and/or MCS. After adjusting for gender, age and disease duration, disease activity impacted on both PCS and MCS and all subscales except general health. Active lupus nephritis and musculoskeletal involvement were associated with physical limitations and emotional problems, increased bodily pain and poor social functioning. Low complement and/or presence of anti-dsDNA antibodies were associated with increased fatigue and reduced mental health. In patients with SLE, HRQoL is reduced in those with active disease. Impact of disease activity on HRQoL dimensions depends on SELENA-SLEDAI system components.

75 FR 35492 - Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus-Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-22

...] Guidance for Industry on Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical... entitled ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for... biological products, and medical devices for the treatment of lupus nephritis (LN) caused by systemic lupus...

Physical activity and risk of type 2 diabetes among Native Hawaiians, Japanese Americans, and Caucasians: the Multiethnic Cohort.

PubMed

Steinbrecher, Astrid; Erber, Eva; Grandinetti, Andrew; Nigg, Claudio; Kolonel, Laurence N; Maskarinec, Gertraud

2012-07-01

Physical inactivity is an established risk factor for diabetes; however, little is known about this association across ethnic groups with different diabetes risk. Therefore, we evaluated the association between physical activity and diabetes and potential effect modification by ethnicity in the Hawaii component of the Multiethnic Cohort. Participants, aged 45 to 75 years, were enrolled by completing a questionnaire on demographics, diet, and self-reported weekly hours of strenuous sports, vigorous work, and moderate activity. Among the 74,913 participants (39% Caucasian, 14% Native Hawaiian, 47% Japanese American), 8561 incident diabetes cases were identified by self-report, a medication questionnaire, and through health plan linkages. Cox regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) while adjusting for known confounders. Engaging in strenuous sports was inversely related to diabetes risk with HRs (4+ hours/week vs. never) of 0.67 (95%CI: 0.57-0.79) in women and 0.80 (95%CI: 0.72-0.88) in men. In stratified analyses, the inverse association was consistent across ethnic groups. The inverse association of vigorous work with diabetes was limited to men, while beneficial effects of moderate activity were observed only in Caucasians. These findings support a role of high-intensity physical activity and ethnic-specific guidelines in diabetes prevention.

I too, am America: a review of research on systemic lupus erythematosus in African-Americans

PubMed Central

Williams, Edith M; Bruner, Larisa; Adkins, Alyssa; Vrana, Caroline; Logan, Ayaba; Kamen, Diane; Oates, James C

2016-01-01

Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder that can cause significant morbidity and mortality. A large body of evidence has shown that African-Americans experience the disease more severely than other racial-ethnic groups. Relevant literature for the years 2000 to August 2015 were obtained from systematic searches of PubMed, Scopus, and the EBSCOHost platform that includes MEDLINE, CINAHL, etc. to evaluate research focused on SLE in African-Americans. Thirty-six of the 1502 articles were classified according to their level of evidence. The systematic review of the literature reported a wide range of adverse outcomes in African-American SLE patients and risk factors observed in other mono and multi-ethnic investigations. Studies limited to African-Americans with SLE identified novel methods for more precise ascertainment of risk and observed novel findings that hadn't been previously reported in African-Americans with SLE. Both environmental and genetic studies included in this review have highlighted unique African-American populations in an attempt to isolate risk attributable to African ancestry and observed increased genetic influence on overall disease in this cohort. The review also revealed emerging research in areas of quality of life, race-tailored interventions, and self-management. This review reemphasizes the importance of additional studies to better elucidate the natural history of SLE in African-Americans and optimize therapeutic strategies for those who are identified as being at high risk. PMID:27651918

Living with Lupus

MedlinePlus

... Loss Dealing with Pain and Fatigue Exercise and Nutrition Family Life and Relationships Financial Resources: Healthcare Finding the Right Doctor Flares How Lupus Affects the Body Lupus and the Workplace Lupus in Men Mental Health and Wellbeing Overlapping ...

Discoid Lupus Erythematosus

MedlinePlus

... Name: Category: Share: Yes No, Keep Private Discoid Lupus Erythematosus Share | Discoid lupus erythematosus (DLE) is a chronic skin condition of ... occur. A small percentage of patients with discoid lupus can develop disease of the internal organs, which ...

Early Prediction of Lupus Nephritis Using Advanced Proteomics

DTIC Science & Technology

2008-06-01

Structure of the Conserved Hypothetical Protein Rv2302 from Mycobacterium tuberculosis ” 188, 5993-6001, J. Bacteriology, 2006. 11. T.A. Ramelot, A. Yee...currently elusive renal biomarkers crucial for the prognosis of SLE. A well-defined cohort of patients with SLE (n=150), disease and healthy...enhanced various TOF- MS, we discovered a set urinary lupus nephritis candidate biomarkers ; namely transferrin, ceruloplasmin, alpha1-acid

Validation of the Lupus Nephritis Clinical Indices in Childhood-Onset Systemic Lupus Erythematosus.

PubMed

Mina, Rina; Abulaban, Khalid; Klein-Gitelman, Marisa S; Eberhard, Barbara A; Ardoin, Stacy P; Singer, Nora; Onel, Karen; Tucker, Lori; O'neil, Kathleen; Wright, Tracey; Brooks, Elizabeth; Rouster-Stevens, Kelly; Jung, Lawrence; Imundo, Lisa; Rovin, Brad; Witte, David; Ying, Jun; Brunner, Hermine I

2016-02-01

To validate clinical indices of lupus nephritis activity and damage when used in children against the criterion standard of kidney biopsy findings. In 83 children requiring kidney biopsy, the Systemic Lupus Erythematosus Disease Activity Index renal domain (SLEDAI-R), British Isles Lupus Assessment Group index renal domain (BILAG-R), Systemic Lupus International Collaborating Clinics (SLICC) renal activity score (SLICC-RAS), and SLICC Damage Index renal domain (SDI-R) were measured. Fixed effects and logistic models were calculated to predict International Society of Nephrology/Renal Pathology Society (ISN/RPS) class; low-to-moderate versus high lupus nephritis activity (National Institutes of Health [NIH] activity index [AI]) score: ≤10 versus >10; tubulointerstitial activity index (TIAI) score: ≤5 versus >5; or the absence versus presence of lupus nephritis chronicity (NIH chronicity index) score: 0 versus ≥1. There were 10, 50, and 23 patients with ISN/RPS class I/II, III/IV, and V, respectively. Scores of the clinical indices did not differentiate among patients by ISN/RPS class. The SLEDAI-R and SLICC-RAS but not the BILAG-R differed with lupus nephritis activity status defined by NIH-AI scores, while only the SLEDAI-R scores differed between lupus nephritis activity status based on TIAI scores. The sensitivity and specificity of the SDI-R to capture lupus nephritis chronicity was 23.5% and 91.7%, respectively. Despite being designed to measure lupus nephritis activity, SLICC-RAS and SLEDAI-R scores significantly differed with lupus nephritis chronicity status. Current clinical indices of lupus nephritis fail to discriminate ISN/RPS class in children. Despite its shortcomings, the SLEDAI-R appears best for measuring lupus nephritis activity in a clinical setting. The SDI-R is a poor correlate of lupus nephritis chronicity. © 2016, American College of Rheumatology.

Characterization of Patients With Lupus Nephritis Included in a Large Cohort From the Spanish Society of Rheumatology Registry of Patients With Systemic Lupus Erythematosus (RELESSER).

PubMed

Galindo-Izquierdo, María; Rodriguez-Almaraz, Esther; Pego-Reigosa, José M; López-Longo, Francisco J; Calvo-Alén, Jaime; Olivé, Alejandro; Fernández-Nebro, Antonio; Martinez-Taboada, Víctor; Vela-Casasempere, Paloma; Freire, Mercedes; Narváez, Francisco J; Rosas, José; Ibáñez-Barceló, Mónica; Uriarte, Esther; Tomero, Eva; Zea, Antonio; Horcada, Loreto; Torrente, Vicenç; Castellvi, Iván; Calvet, Joan; Menor-Almagro, Raúl; Zamorano, María A Aguirre; Raya, Enrique; Díez-Álvarez, Elvira; Vázquez-Rodríguez, Tomás; García de la Peña, Paloma; Movasat, Atusa; Andreu, José L; Richi, Patricia; Marras, Carlos; Montilla-Morales, Carlos; Hernández-Cruz, Blanca; Marenco de la Fuente, José L; Gantes, María; Úcar, Eduardo; Alegre-Sancho, Juan J; Manero, Javier; Ibáñez-Ruán, Jesús; Rodríguez-Gómez, Manuel; Quevedo, Víctor; Hernández-Beriaín, José; Silva-Fernández, Lucía; Alonso, Fernando; Pérez, Sabina; Rúa-Figueroa, Iñigo

2016-03-01

The aim of the study was to profile those patients included in the RELESSER registry with histologically proven renal involvement in order to better understand the current state of lupus nephritis (LN) in Spain. RELESSER-TRANS is a multicenter cross-sectional registry with an analytical component. Information was collected from the medical records of patients with systemic lupus erythematosus who were followed at participating rheumatology units. A total of 359 variables including demographic data, clinical manifestations, disease activity, severity, comorbidities, LN outcome, treatments, and mortality were recorded. Only patients with a histological confirmation of LN were included. We performed a descriptive analysis, chi-square or Student's t tests according to the type of variable and its relationship with LN. Odds ratio and confidence intervals were calculated by using simple logistic regression. LN was histologically confirmed in 1092/3575 patients (30.5%). Most patients were female (85.7%), Caucasian (90.2%), and the mean age at LN diagnosis was 28.4 ± 12.7 years. The risk for LN development was higher in men (M/F:47.85/30.91%, P < 0.001), in younger individuals (P < 0.001), and in Hispanics (P = 0.03). Complete response to treatment was achieved in 68.3% of patients; 10.35% developed ESRD, which required a kidney transplant in 45% of such cases. The older the patient, the greater was the likelihood of complete response (P < 0.001). Recurrences were associated with persistent lupus activity at the time of the last visit (P < 0.001) and with ESRD (P < 0.001). Thrombotic microangiopathy was a risk factor for ESRD (P = 0.04), as for the necessity of dialysis (P = 0.01) or renal transplantation (P = 0.03). LN itself was a poor prognostic risk factor of mortality (OR 2.4 [1.81-3.22], P < 0.001). Patients receiving antimalarials had a significantly lower risk of developing LN (P < 0.001) and ESRD (P < 0

Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs. Nurture.

PubMed

Alarcón, G S; Friedman, A W; Straaton, K V; Moulds, J M; Lisse, J; Bastian, H M; McGwin, G; Bartolucci, A A; Roseman, J M; Reveille, J D

1999-01-01

To determine and contrast the socioeconomic-demographic and clinical features of patients with recent onset (< or =5 y) systemic lupus erythematosus (SLE) from three ethnic groups, Hispanic, African-American and Caucasian (H, AA, C). SLE cases (American College of Rheumatology criteria) (incident (n = 56), prevalent (n = 173)), were enrolled in a longitudinal study at The University of Alabama at Birmingham, The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston. Socioeconomic-demographic, clinical, immunological, behavioral and psychological data were obtained using validated instruments and standard laboratory techniques, and compared. 70 H, 88 AA and 71 C SLE patients constitute this cohort. H and AA patients were younger and of lower socioeconomic-demographic status. They also had evidence of more frequent organ system involvement (renal, cardiovascular), more auto-antibodies, more active disease (after adjusting for discrepant socioeconomic-demographic features), lower levels of social support and more abnormal illness-related behaviors (more in H than in AA). H also were more likely to have an abrupt disease onset; C were more likely to be on antimalarials but less likely to be on corticosteroids. H, AA, and C used health care resources comparably. They had similar levels of pain and physical and mental functioning after adjusting for age, disease duration, income, education, social support, illness-related behaviors, and Systemic Lupus Activity Measure or SLAM scores. H and AA patients have more active SLE, at an earlier age of onset, and a less favorable socioeconomic-demographic structure (worse among the H than AA) which predispose them to a less favorable natural history.

Evaluation of germline BRCA1 and BRCA2 mutations in a multi-ethnic Asian cohort of ovarian cancer patients.

PubMed

Hasmad, Hanis Nazihah; Lai, Kah Nyin; Wen, Wei Xiong; Park, Daniel Jonathan; Nguyen-Dumont, Tú; Kang, Peter Choon Eng; Thirthagiri, Eswary; Ma'som, Mahirah; Lim, Boon Kiong; Southey, Melissa; Woo, Yin Ling; Teo, Soo-Hwang

2016-05-01

Despite the discovery of breast and ovarian cancer predisposition genes BRCA1 and BRCA2 more than two decades ago, almost all the available data relate to women of European ancestry, with only a handful of studies in Asian populations. In this study, we determined the frequency of germline alterations in BRCA1 and BRCA2 in ovarian cancer patients from a multi-ethnic cross-sectional cohort of Asian ovarian cancer patients from Malaysia. From October 2008 to February 2015, we established a hospital-based cohort of ovarian cancer patients and the germline status of all 218 women with invasive epithelial ovarian cancer was tested using targeted amplification and sequencing of the intron-exon junctions and exonic sequences of BRCA1, BRCA2, PALB2 and TP53. BRCA1 and BRCA2 mutations were found in 8% (17 cases) and 3% (7 cases) of the ovarian cancer patients, respectively. Mutation carriers were diagnosed at a similar age to non-carriers, but were more likely to be Indian, have serous ovarian cancer, and have more relatives with breast or ovarian cancer. Nonetheless, 42% (10/24) of mutation carriers did not have any family history of breast or ovarian cancer and offering genetic counselling and genetic testing only to women with family history would mean that 35% (6/17) of BRCA1 mutation carriers and 57% (4/7) of BRCA2 mutation carriers would not be offered genetic testing. Our data suggest that, similar to Caucasians, a significant proportion of Asian ovarian cancer was attributed to germline mutations in BRCA1 and to a lesser extent in BRCA2. Copyright © 2015. Published by Elsevier Inc.

Analysis of the New Zealand Black contribution to lupus-like renal disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drake, C.G.; Rozzo, S.J.; Hirschfeld, H.F.

1995-03-01

F{sub 1} progeny of New Zealand Black (NZB) and New Zealand White (NZW) mice spontaneously develop an autoimmune process remarkably similar to human systemic lupus erythematosus. Previous studies have implicated major genetic contributions from the NZW MHC and from a dominant NZB gene on chromosome 4. To identify additional NZB contributions to lupus-like disease, (NZB x SM/J)F{sub 1} x NZW backcross mice were followed for the development of severe renal disease and were comprehensively genotyped. Despite a 50% incidence of disease significant associations between the presence of the NZB genotype and disease were noted on chromosomes 1, 4, 7, 10,more » 13, and 19. The data indicated that multiple NZB genes, in different combinations, contribute to severe renal disease, and that no single gene is required. To further investigate this NZB contribution, NZB x SM/J (NXSM) recombinant inbred (RI) strains were crossed with NZW mice, and F{sub 1} progeny were analyzed for the presence of lupus-like renal disease. Interestingly, nearly all of the (RI x NZW)F{sub 1} cohorts studies expressed some level of disease. Five RI strains generated a high incidence of disease, similar to (NZB x NZW)F{sub 1} mice, and nearly one-half of the cohorts developed disease at intermediate levels. Only two cohorts demonstrated very little disease, supporting the conclusion that multiple genes are capable of disease induction. Experiments correlating the genotypes of these RI strains with their ability to generate disease revealed that none of the disease-associated loci defined by the backcross analysis were present in all five RI strains that generated disease at high levels. Overall, both the backcross data and RI analysis provide additional support for the genetic complexity of lupus nephritis and uphold the conclusion that heterogeneous combinations of contributing NZB genes seem to operate in a threshold manner to generate the disease phenotype. 31 refs., 3 figs., 2 tabs.« less

Multiethnic GWAS Reveals Polygenic Architecture of Earlobe Attachment.

PubMed

Shaffer, John R; Li, Jinxi; Lee, Myoung Keun; Roosenboom, Jasmien; Orlova, Ekaterina; Adhikari, Kaustabh; Gallo, Carla; Poletti, Giovanni; Schuler-Faccini, Lavinia; Bortolini, Maria-Cátira; Canizales-Quinteros, Samuel; Rothhammer, Francisco; Bedoya, Gabriel; González-José, Rolando; Pfeffer, Paige E; Wollenschlaeger, Christopher A; Hecht, Jacqueline T; Wehby, George L; Moreno, Lina M; Ding, Anan; Jin, Li; Yang, Yajun; Carlson, Jenna C; Leslie, Elizabeth J; Feingold, Eleanor; Marazita, Mary L; Hinds, David A; Cox, Timothy C; Wang, Sijia; Ruiz-Linares, Andrés; Weinberg, Seth M

2017-12-07

The genetic basis of earlobe attachment has been a matter of debate since the early 20 th century, such that geneticists argue both for and against polygenic inheritance. Recent genetic studies have identified a few loci associated with the trait, but large-scale analyses are still lacking. Here, we performed a genome-wide association study of lobe attachment in a multiethnic sample of 74,660 individuals from four cohorts (three with the trait scored by an expert rater and one with the trait self-reported). Meta-analysis of the three expert-rater-scored cohorts revealed six associated loci harboring numerous candidate genes, including EDAR, SP5, MRPS22, ADGRG6 (GPR126), KIAA1217, and PAX9. The large self-reported 23andMe cohort recapitulated each of these six loci. Moreover, meta-analysis across all four cohorts revealed a total of 49 significant (p < 5 × 10 -8 ) loci. Annotation and enrichment analyses of these 49 loci showed strong evidence of genes involved in ear development and syndromes with auricular phenotypes. RNA sequencing data from both human fetal ear and mouse second branchial arch tissue confirmed that genes located among associated loci showed evidence of expression. These results provide strong evidence for the polygenic nature of earlobe attachment and offer insights into the biological basis of normal and abnormal ear development. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER).

PubMed

Torrente-Segarra, Vicenç; Salman Monte, Tarek Carlos; Rúa-Figueroa, Iñigo; Sánchez-Alonso, Fernando; López-Longo, Francisco Javier; Galindo-Izquierdo, María; Calvo-Alén, Jaime; Olivé-Marqués, Alejandro; Ibañez-Ruán, Jesús; Horcada, Loreto; Sánchez-Atrio, Ana; Montilla, Carlos; Melero González, Rafael Benito; Díez-Álvarez, Elvira; Martinez-Taboada, Victor; Andreu, José Luis; Fernández-Berrizbeitia, Olaia; Hernández-Beriain, José Ángel; Gantes, Marian; Hernández-Cruz, Blanca; Pecondón-Español, Ángela; Marras, Carlos; Bonilla, Gema; Pego-Reigosa, José M

2017-01-01

We aimed to describe juvenile-onset systemic lupus erythematosus (jSLE) features and to establish its differences compared to adult-onset SLE (aSLE) from a large national database. Data from patients (≥4 ACR criteria) included in Spanish Society of Rheumatology Lupus Registry (RELESSER) were analysed. Sociodemographic, clinical, serological, activity, treatment, cumulative damage, comorbidities and severity data were collected. Patients with disease onset <18 years were described and compared to those with disease onset ≥18 years. We reviewed 3,428 aSLE patients (89.6% women) and 484 jSLE patients (89.8% girls), 93% Caucasian (both groups). Mean age at diagnosis was 38.1±14 and 16.6±6.3 years (p<0.001) and mean age at the end of follow-up was 48.8±14.3 and 31.5±30 years (p<0.001), respectively. jSLE showed significantly more clinical (including lymphadenopathy, fever, malar rash, mucosal ulcers, pericarditis, pleuritis, Raynaud's phenomenon, lupus nephritis, recurrent nephritis, histologic nephritis changes, thrombocytopenia, haemolytic anaemia, thrombotic thrombocytopenic purpura, seizures, lupus headache and organic brain syndrome) and immunological (a-dsDNA and a-Sm antibodies, hypocomplementaemia) involvement than did aSLE, except for secondary Sjögren's syndrome, a-Ro antibodies, fibromyalgia and osteoporosis. jSLE also showed more SLE family history, longer diagnosis delay, higher SLEDAI and Katz scores, but lower Charlson scores than aSLE. Several specific domains were more frequently involved in SLICC/ACR DI in jSLE. jSLE patients more frequently underwent all SLE-related treatment and procedures, as well as dialysis and kidney transplantations. jSLE shares many clinical and serological features with aSLE. However, jSLE patients typically manifested more activity, severity, cumulative damage in certain areas, than their aSLE counterparts.

Impact of Replacing the Pooled Cohort Equation With Other Cardiovascular Disease Risk Scores on Atherosclerotic Cardiovascular Disease Risk Assessment (from the Multi-Ethnic Study of Atherosclerosis [MESA]).

PubMed

Qureshi, Waqas T; Michos, Erin D; Flueckiger, Peter; Blaha, Michael; Sandfort, Veit; Herrington, David M; Burke, Gregory; Yeboah, Joseph

2016-09-01

The increase in statin eligibility by the new cholesterol guidelines is mostly driven by the Pooled Cohort Equation (PCE) criterion (≥7.5% 10-year PCE). The impact of replacing the PCE with either the modified Framingham Risk Score (FRS) or the Systematic Coronary Risk Evaluation (SCORE) on assessment of atherosclerotic cardiovascular disease (ASCVD) risk assessment and statin eligibility remains unknown. We assessed the comparative benefits of using the PCE, FRS, and SCORE for ASCVD risk assessment in the Multi-Ethnic Study of Atherosclerosis. Of 6,815 participants, 654 (mean age 61.4 ± 10.3; 47.1% men; 37.1% whites; 27.2% blacks; 22.3% Hispanics; 12.0% Chinese-Americans) were included in analysis. Area under the curve (AUC) and decision curve analysis were used to compare the 3 risk scores. Decision curve analysis is the plot of net benefit versus probability thresholds; net benefit = true positive rate - (false positive rate × weighting factor). Weighting factor = Threshold probability/1 - threshold probability. After a median of 8.6 years, 342 (6.0%) ASCVD events (myocardial infarction, coronary heart disease death, fatal or nonfatal stroke) occurred. All 4 risk scores had acceptable discriminative ability for incident ASCVD events; (AUC [95% CI] PCE: 0.737 [0.713 to 0.762]; FRS: 0.717 [0.691 to 0.743], SCORE (high risk) 0.722 [0.696 to 0.747], and SCORE (low risk): 0.721 [0.696 to 0.746]. At the ASCVD risk threshold recommended for statin eligibility for primary prevention (≥7.5%), the PCE provides the best net benefit. Replacing the PCE with the SCORE (high), SCORE (low) and FRS results in a 2.9%, 8.9%, and 17.1% further increase in statin eligibility. The PCE has the best discrimination and net benefit for primary ASCVD risk assessment in a US-based multiethnic cohort compared with the SCORE or the FRS. Copyright © 2016 Elsevier Inc. All rights reserved.

Lupus anticoagulants and antiphospholipid antibodies

MedlinePlus

Blood clots - lupus anticoagulants; DVT - anticoagulants ... Most often, lupus anticoagulants and aPL are found in people with diseases such as systemic lupus erythematosus (SLE). Lupus anticoagulants and ...

Lupus cystitis in Korean patients with systemic lupus erythematosus: risk factors and clinical outcomes.

PubMed

Koh, J H; Lee, J; Jung, S M; Ju, J H; Park, S-H; Kim, H-Y; Kwok, S-K

2015-10-01

This study was performed to investigate the clinical characteristics of lupus cystitis and determine the risk factors and clinical outcomes of lupus cystitis in patients with systemic lupus erythematosus (SLE). We retrospectively reviewed 1064 patients at Seoul St. Mary's Hospital in Seoul, Korea, from 1998 to 2013. Twenty-four patients had lupus cystitis. Lupus cystitis was defined as unexplained ureteritis and/or cystitis as detected by imaging studies, cystoscopy, or bladder histopathology without urinary microorganisms or stones. Three-fourths of patients with lupus cystitis had concurrent lupus mesenteric vasculitis (LMV). The initial symptoms were gastrointestinal in nature for most patients (79.2%). High-dose methylprednisolone was initially administered to most patients (91.7%) with lupus cystitis. Two patients (8.3%) died of urinary tract infections. Sixty-five age- and sex-matched patients with SLE who were admitted with other manifestations were included as the control group. Patients with lupus cystitis showed a lower C3 level (p = 0.031), higher SLE Disease Activity Index score (p = 0.006), and higher ESR (p = 0.05) upon admission; more frequently had a history of LMV prior to admission (p < 0.001); and less frequently had a history of neuropsychiatric lupus (p = 0.031) than did patients with SLE but without lupus cystitis. The occurrence of lupus cystitis was associated with a history of LMV (OR, 21.794; 95% CI, 4.061-116.963). The median follow-up period was 3.4 years, and the cumulative one-year mortality rate was 20%. Complications developed in 33.3% of patients with lupus cystitis and were related to survival (log-rank p = 0.021). Our results suggest that the possibility of lupus cystitis should be considered when a patient with SLE and history of LMV presents with gastrointestinal symptoms or lower urinary tract symptoms. Development of complications in patients with lupus cystitis can be fatal. Thus, intensive treatment

Ethnic differences in DNA methyltransferases expression in patients with systemic lupus erythematosus.

PubMed

Wiley, Kenneth L; Treadwell, Edward; Manigaba, Kayihura; Word, Beverly; Lyn-Cook, Beverly D

2013-02-01

Systemic lupus erythematous (SLE) is a systemic autoimmune inflammatory disease with both genetic and epigenetic etiologies. Evidence suggests that deregulation of specific genes through epigenetic mechanisms may be a contributing factor to SLE pathology. There is increasing evidence that DNA methyltransferase activity may be involved. This study demonstrated modulation in expression of DNA methyltransferases (DNMTs) according to ethnicity in patients diagnosed with SLE. Furthermore, differential expression in one of the DNMTs was found in a subset of lupus patients on dehydroepiandrosterone (DHEA) therapy. Real-time PCR analyses of DNMT1, DNMT3A and DNMT3B in peripheral blood mononuclear cells from a cohort of African American and European American lupus and non-lupus women were conducted. Also, global DNA methylation was assessed using the MethylFlash(TM) methylated quantification colorimetric assay. Significant increase in DNMT3A (p < 0.001) was shown in lupus patients when compared to age-matched healthy controls. This increase was associated with a higher SLEDI index. More striking was that expression levels for African American (AA) women were higher than European American women in the lupus populations. A subset of AA women on DHEA therapy showed a significant decrease (p < 0.05) in DNMT3A expression in comparison to lupus patients not on the therapy. DHEA is an androgenic steroid found in low levels in the serum of lupus patients. Supplementation of this hormone has been shown to be beneficial to some lupus patients. DHEA was not shown to effect DNMT1 or DNMT3B expression. Increased expression was also noted in DNMT3B (p < 0.05) in lupus patients compared to age-matched healthy controls. However, no significant difference was noted in DNMT1 (p = 0.2148) expression between lupus patients and healthy controls. Although increases were detected in de novo methyltransferases, a global decrease (p < 0.001) in 5-methycytosine was observed in

TAC-TIC use of tacrolimus-based regimens in lupus nephritis

PubMed Central

Bredewold, Obbo W; Trompet, Stella; Huizinga, Tom W J; Rabelink, Ton J; de Craen, Anton J M; Teng, Y K Onno

2016-01-01

Current guidelines do not mention tacrolimus (TAC) as a treatment option and no consensus has been reported on the role of TAC in lupus nephritis (LN). The present study aimed to guide clinical judgement on the use of TAC in patients with LN. A meta-analysis was performed for clinical studies investigating TAC regimens in LN on the basis of treatment target (induction or maintenance), concomitant immunosuppression and quality of the data. 23 clinical studies performed in patients with LN were identified: 6 case series, 9 cohort studies, 2 case-control studies and 6 randomised controlled trials (RCTs). Of the 6 RCTs, 5 RCTs investigated TAC regimens as induction treatment and 1 RCT as maintenance treatment. Five RCTs investigated TAC in combination with steroids and 2 TAC with mycophenolate plus steroids. All RCTs were performed in patients of Asian ethnicity. In a meta-analysis, TAC regimens achieved a significantly higher total response (relative risk (RR) 1.23, 95% CI 1.12 to 1.34, p<0.05) and significantly higher complete response (RR 1.48, 95% CI 1.23 to 1.77, p<0.05). The positive outcome was predominantly defined by the largest RCT investigating TAC with mycophenolate plus steroids. Regarding safety, the occurrence of leucopoenia was significantly lower, while the occurrence of increased creatine was higher. Clinical studies on TAC regimens for LN are limited to patients of Asian ethnicity and hampered by significant heterogeneity. The positive results on clinical efficacy of TAC as induction treatment in LN cannot be extrapolated beyond Asian patients with LN. Therefore, further confirmation in multiethnic, randomised trials is mandatory. Until then, TAC can be considered in selected patients with LN. PMID:28123768

Genetic association of CD247 (CD3ζ) with SLE in a large-scale multiethnic study.

PubMed

Martins, M; Williams, A H; Comeau, M; Marion, M; Ziegler, J T; Freedman, B I; Merrill, J T; Glenn, S B; Kelly, J A; Sivils, K M; James, J A; Guthridge, J M; Alarcón-Riquelme, M E; Bae, S-C; Kim, J-H; Kim, D; Anaya, J-M; Boackle, S A; Criswell, L A; Kimberly, R P; Alarcón, G S; Brown, E E; Vilá, L M; Petri, M A; Ramsey-Goldman, R; Niewold, T B; Tsao, B P; Gilkeson, G S; Kamen, D L; Jacob, C O; Stevens, A M; Gaffney, P M; Harley, J B; Langefeld, C D; Fesel, C

2015-03-01

A classic T-cell phenotype in systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters T-cell receptor signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multiethnic population. We typed 44 contiguous CD247 single-nucleotide polymorphisms (SNPs) in 8922 SLE patients and 8077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99 × 10(-4) < P < 4.15 × 10(-2)), where we further identified a five-marker haplotype (rs12141731-rs2949655-rs16859085-rs12144621-rs858554; G-G-A-G-A; P(hap) = 2.12 × 10(-5)) that exceeded the most associated single SNP rs858554 (minor allele frequency in controls = 13%; P = 4.99 × 10(-4), odds ratio = 1.32) in significance. Imputation and subsequent association analysis showed evidence of association (P < 0.05) at 27 additional SNPs within intron 1. Cross-ethnic meta-analysis, assuming an additive genetic model adjusted for population proportions, showed five SNPs with significant P-values (1.40 × 10(-3) < P< 3.97 × 10(-2)), with one (rs704848) remaining significant after Bonferroni correction (P(meta) = 2.66 × 10(-2)). Our study independently confirms and extends the association of SLE with CD247, which is shared by various autoimmune disorders and supports a common T-cell-mediated mechanism.

Genetic Association of CD247 (CD3ζ) with SLE in a Large-Scale Multiethnic Study

PubMed Central

Martins, Madalena; Williams, Adrienne H.; Comeau, Mary; Marion, Miranda; Ziegler, Julie T.; Freedman, Barry I.; Merrill, Joan T.; Glenn, Stuart B.; Kelly, Jennifer A.; Sivils, Kathy M.; James, Judith A.; Guthridge, Joel M.; Alarcón-Riquelme, Marta E.; Bae, Sang-Cheol; Kim, Jae-Hoon; Kim, Dam; Anaya, Juan-Manuel; Boackle, Susan A.; Criswell, Lindsey A.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.; Vilá, Luis M.; Petri, Michelle A.; Ramsey-Goldman, Rosalind; Niewold, Timothy B.; Tsao, Betty P.; Gilkeson, Gary S.; Kamen, Diane L.; Jacob, Chaim O.; Stevens, Anne M.; Gaffney, Patrick M.; Harley, John B.; Langefeld, Carl D.; Fesel, Constantin

2015-01-01

A classic T-cell phenotype in Systemic lupus erythematosus (SLE) is the downregulation and replacement of the CD3ζ chain that alters TCR signaling. However, genetic associations with SLE in the human CD247 locus that encodes CD3ζ are not well established and require replication in independent cohorts. Our aim was therefore to examine, localize and validate CD247-SLE association in a large multi-ethnic population. We typed 44 contiguous CD247 SNPs in 8 922 SLE patients and 8 077 controls from four ethnically distinct populations. The strongest associations were found in the Asian population (11 SNPs in intron 1, 4.99×10−4

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

PubMed

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

PubMed

Bastian, H M; Roseman, J M; McGwin, G; Alarcón, G S; Friedman, A W; Fessler, B J; Baethge, B A; Reveille, J D

2002-01-01

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95

Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort.

PubMed

Riveros Frutos, A; Casas, I; Rúa-Figueroa, I; López-Longo, F J; Calvo-Alén, J; Galindo, M; Fernández-Nebro, A; Pego-Reigosa, J M; Olivé Marqués, A

2017-06-01

Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18-92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p < 0.001). Males were diagnosed earlier than females (p = 0.04) and had more cardiovascular comorbidities ( p < 0.001). Two hundred and thirty-six males (68%) with SLE required hospitalization in comparison with 1713 females (53%) ( p < 0.001). During follow-up, 208 patients died: 30 men (9.3%) and 178 women (5.9%) ( p = 0.02). As regards clinical manifestations, loss of weight ( p = 0.01), lymphadenopathies ( p = 0.02), and splenomegaly ( p = 0.02) were more common in male patients. Female patients were more likely to have inflammatory rash, alopecia, and arthritis ( p < 0.05). As for lung involvement, men with SLE had more pleural fibrosis ( p < 0.001) and pulmonary embolism ( p = 0.01). However, Raynaud's phenomenon was more common in women (35%) than in men (23.7%) ( p < 0.001); lupus nephritis was more common in men, being present in 155 (44.8%) of males versus 933 (29%) of females ( p < 0.001). Multivariate analysis showed that SLE patients with a high Charlson index (more than 3 points) and age > 50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50

IRF5, PTPN22, CD28, IL2RA, KIF5A, BLK and TNFAIP3 genes polymorphisms and lupus susceptibility in a cohort from the Egypt Delta; relation to other ethnic groups.

PubMed

Elghzaly, Ashraf A; Metwally, Shereen S; El-Chennawi, Farha A; Elgayaar, Maha A; Mosaad, Youssef M; El-Toraby, Ehab E; Hegab, Mohsen M; Ibrahim, Saleh M

2015-07-01

To replicate a single nucleotide polymorphism (SNP) of known genes for lupus (IRF5 rs10488631, PTPN22 rs2476601, BLK rs2736340 and TNFAIP3 rs5029939) and other autoimmune diseases (CD28 rs1980422, IL2RA rs2104286 and KIF5A rs1678542) on a newly studied Egyptian cohort to investigate the genetic disparity with different studied ethnic groups in relation to lupus susceptibility. 170 Egyptian patients from Egypt Delta with SLE and 241 matched healthy controls were genotyped by Taqman real time PCR for the selected SNPs. The results revealed significant association with IRF5 (p<0.0001) and PTPN22 (p=0.008) and insignificant association with KIF5A, CD28, IL2RA, BLK and TNFAIP3 genes. This study may provide an additional evidence for the association between IRF5 and PTPN22 and lupus susceptibility and may exclude it for CD28, IL2RA, and KIF5A. Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Cardiovascular outcomes of a positive nuclear stress test but negative coronary angiography in a multiethnic male predominant cohort.

PubMed

Addison, Daniel; Singh, Vinita; Okyere-Asante, K; Okafor, Henry

2014-01-01

Patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging (MPI), but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma. They are often dismissed as having 'false-positive MPI'. Moreover, a majority of the available long-term outcome data for it has been derived from homogenous female populations. In this study, we sought to evaluate the long-term outcomes of this presentation in a multiethnic male-predominant cohort. We retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on MPI, but with no significant angiographic disease on subsequent cardiac catheterization (cases). The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute myocardial infarction and stroke) post-index coronary angiogram was tracked. Similar data was collected for 37 patients who also presented with chest pain, but normal MPI over the same period (controls). Overall average follow-up was over 22 months. Fifty-three percent (26/47) of the cases had one or more of the adverse outcomes as compared with 22% (8/37) of controls (P < 0.01). Of these, 13 (50.0%) and 3 (37.5%) were males, respectively. Ischemia on MPI is predictive of long-term adverse cardiovascular outcomes despite normal ('false-negative') coronary angiography. This appears to be gender-neutral.

Cardiovascular outcomes of a positive nuclear stress test but negative coronary angiography in a multiethnic male predominant cohort

PubMed Central

Addison, Daniel; Singh, Vinita; Okyere-Asante, K; Okafor, Henry

2014-01-01

Background: Patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging (MPI), but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma. They are often dismissed as having ‘false-positive MPI’. Moreover, a majority of the available long-term outcome data for it has been derived from homogenous female populations. In this study, we sought to evaluate the long-term outcomes of this presentation in a multiethnic male-predominant cohort. Materials and Methods: We retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on MPI, but with no significant angiographic disease on subsequent cardiac catheterization (cases). The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute myocardial infarction and stroke) post-index coronary angiogram was tracked. Similar data was collected for 37 patients who also presented with chest pain, but normal MPI over the same period (controls). Overall average follow-up was over 22 months. Results: Fifty-three percent (26/47) of the cases had one or more of the adverse outcomes as compared with 22% (8/37) of controls (P < 0.01). Of these, 13 (50.0%) and 3 (37.5%) were males, respectively. Conclusions: Ischemia on MPI is predictive of long-term adverse cardiovascular outcomes despite normal (‘false-negative’) coronary angiography. This appears to be gender-neutral. PMID:24970963

PKK deficiency in B cells prevents lupus development in Sle lupus mice

PubMed Central

Oleksyn, D.; Zhao, J.; Vosoughi, A.; Zhao, JC.; Misra, R; Pentland, AP; Ryan, D.; Anolik, J.; Ritchlin, C.; Looney, J.; Anandarajah, AP.; Schwartz, G.; Calvi, LM; Georger, M; Mohan, C.; Sanz, I.; Chen, L

2018-01-01

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the production of autoantibodies that can result in damage to multiple organs. It is well documented that B cells play a critical role in the development of the disease. We previously showed that protein kinase C associated kinase (PKK) is required for B1 cell development as well as for the survival of recirculating mature B cells and B- lymphoma cells. Here, we investigated the role of PKK in lupus development in a lupus mouse model. We demonstrate that the conditional deletion of PKK in B cells prevents lupus development in Sle1Sle3 mice. The loss of PKK in Sle mice resulted in the amelioration of multiple classical lupus-associated phenotypes and histologic features of lupus nephritis, including marked reduction in the levels of serum autoantibodies, proteinuria, spleen size, peritoneal B-1 cell population and the number of activated CD4 T cells. In addition, the abundance of autoreactive plasma cells normally seen in Sle lupus mice was also significantly decreased in the PKK-deficient Sle mice. Sle B cells deficient in PKK display defective proliferation responses to BCR and LPS stimulation. Consistently, B cell receptor-mediated NF-κB activation, which is required for the survival of activated B cells, was impaired in the PKK-deficient B cells. Taken together, our work uncovers a critical role of PKK in lupus development and suggests that targeting the PKK-mediated pathway may represent a promising therapeutic strategy for lupus treatment. PMID:28274793

Hydroxychloroquine and pregnancy on lupus flares in Korean patients with systemic lupus erythematosus.

PubMed

Koh, J H; Ko, H S; Kwok, S-K; Ju, J H; Park, S-H

2015-02-01

We investigated the clinical and laboratory characteristics of pregnancies with systemic lupus erythematosus (SLE) and identified lupus flare predictors during pregnancy. Additionally, we examined lupus activity and pregnancy outcomes in SLE patients who continued, discontinued or underwent no hydroxychloroquine (HCQ) treatment during pregnancy. We retrospectively analyzed 179 pregnancies in 128 SLE patients at Seoul St. Mary's Hospital, Korea, between 1998 and 2012 and then assessed the clinical profiles and maternal and fetal outcomes. Overall, 90.5% of pregnancies resulted in a successful delivery and were divided into two groups: those who experienced lupus flares (80 pregnancies, 44.7%) and those who did not (99 pregnancies, 55.3%). Increased preeclampsia, preterm births, low birth weight, intrauterine growth restriction (IUGR), and low 1-minute Apgar scores occurred in pregnancies with lupus flares compared to pregnancies in quiescent disease. Lupus flares were predicted by HCQ discontinuation, a history of lupus nephritis, high pre-pregnancy serum uric acid and low C4 levels. Our study indicates that achieving pre-pregnancy remission and continuing HCQ treatment during pregnancy are important for preventing lupus flares. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Cutaneous Lupus Erythematosus: Diagnosis and treatment

PubMed Central

Okon, Lauren G.; Werth, Victoria P.

2013-01-01

Cutaneous lupus erythematosus encompasses a wide range of dermatologic manifestations, which may or may not be associated with the development of systemic disease. Cutaneous lupus is divided into several subtypes, including acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus. Chronic cutaneous lupus erythematosus includes discoid lupus erythematosus, lupus erythematosus profundus, chilblain cutaneous lupus, and lupus tumidus. Diagnosis of these diseases requires proper classification of the subtype, through a combination of physical exam, laboratory studies, histology, antibody serology, and occasionally direct immunofluorescence, while ensuring to exclude systemic disease. Treatment of cutaneous lupus consists of patient education on proper sun protection along with appropriate topical and systemic agents. Systemic agents are indicated in cases of widespread, scarring, or treatment-refractory disease. In this review, we discuss issues in classification and diagnosis of the various subtypes of CLE, as well as provide an update on therapeutic management. PMID:24238695

Neuropsychiatric Features of a Cohort of Patients with Systemic Lupus Erythematosus

PubMed Central

Moraes-Fontes, Maria Francisca; Lúcio, Isabel; Santos, Céu; Campos, Maria Manuel; Riso, Nuno; Vaz Riscado, Manuel

2012-01-01

In order to establish if neuropsychiatric systemic lupus erythematosus (NPSLE) can be identified by any characteristic other than those used to diagnose the neuropsychiatric (NP) disease itself, we retrospectively reviewed 98 systemic lupus erythematosus (SLE) patients followed over a mean period of 10 years. NPSLE was identified in 22 patients. Stroke and generalized seizures were the most frequent NP manifestations. The NPSLE and non-NPSLE groups were similar with regard to demographic characteristics, ACR criteria, serum autoantibodies, and frequency of hypertension and hypercholesterolemia. Of note, compared to the non-NPSLE group, NPSLE was associated with a higher frequency of smoking (78 versus 26%), organ damage (73 versus 34%), and cumulative mortality rate (14 versus 7%). The series of patients was further analysed according to the presence of antiphospholipid syndrome (APS). Significantly, the interval between the onset of NP disease and SLE diagnosis was shorter in the APS− (0.3 ± 1 years) than in the APS+ (5 ± 7 years) groups. Recurrence and/or persistence of NP events were only documented in the APS− group. Overall cumulative mortality was highest in NPSLE and in APS+ patients with inadequate anticoagulation control, identifying an aspect that requires improved vigilance and the development of novel therapeutic modalities. PMID:23227358

77 FR 38305 - Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus-Developing...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... ``Lupus Nephritis Caused By Systemic Lupus Erythematosus--Developing Medical Products for Treatment...] Guidance for Industry on Lupus Nephritis Caused by Systemic Lupus Erythematosus--Developing Medical Products for Treatment; Withdrawal of Guidance AGENCY: Food and Drug Administration, HHS. ACTION: Notice...

Serious Infections among Adult Medicaid Beneficiaries with Systemic Lupus Erythematosus and Lupus Nephritis

PubMed Central

Feldman, Candace H.; Hiraki, Linda T.; Winkelmayer, Wolfgang C.; Marty, Francisco M.; Franklin, Jessica M.; Kim, Seoyoung C.; Costenbader, Karen H.

2015-01-01

Objective While serious infections are significant causes of morbidity and mortality in systemic lupus erythematosus (SLE), the epidemiology in a nationwide cohort of SLE and lupus nephritis (LN) patients has not been examined. Methods Using the Medicaid Analytic eXtract (MAX) database, 2000-2006, we identified patients 18-64 years with SLE and a subset with LN. We ascertained hospitalized serious infections using validated algorithms, and 30-day mortality rates. We used Poisson regression to calculate infection incidence rates (IR), and multivariable Cox proportional hazards models to calculate hazard ratios (HR) for first infection, adjusted for sociodemographics, medication use, and a SLE-specific risk adjustment index. Results We identified 33,565 patients with SLE and 7,113 with LN. There were 9,078 serious infections in 5,078 SLE patients and 3,494 infections in 1,825 LN patients. The infection IR per 100 person-years was 10.8 in SLE and 23.9 in LN. In adjusted models, in SLE, we observed increased risks of infection among males compared to females (HR 1.33, 95% CI 1.20-1.47), in Blacks compared to Whites (HR 1.14, 95% CI 1.06-1.21), and glucocorticoid users (HR 1.51, 95% CI 1.43-1.61) and immunosuppressive users (HR 1.11, 95% CI 1.03-1.20) compared with non-users. Hydroxychloroquine users had a reduced risk of infection compared to non-users (HR 0.73, 95% CI 0.68-0.77). The 30-day mortality rate per 1,000 person-years among those hospitalized with infections was 21.4 in SLE and 38.7 in LN. Conclusion In this diverse, nationwide cohort of SLE patients, we observed a substantial burden of serious infections with many subsequent deaths. PMID:25772621

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus.

PubMed

Yong, Jim Lc; Killingsworth, Murray C; Lai, Ken

2013-01-01

The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE) are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes. Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander. Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease. Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there was no relationship between sex, race, or age and severity of disease.

Burden of lupus on work: Issues in the employment of individuals with lupus.

PubMed

Agarwal, Neelam; Kumar, Vinod

2016-10-17

Systemic lupus erythematosus (SLE) or Lupus is one of the leading causes of work disability in the United States, accounting for about 20% of the more than estimated 1.5 million Americans with a work disability. The symptoms of lupus can have a profound impact on the person's employment. Impacts of lupus are more pronounced among young and middle-adulthood. Studies have shown that loss in work hours cost the nation nearly $13 billion annually. The loss also impacts the individual's work, quality of life, self-management, and self-efficacy. In this article, the author describes the financial burden of lupus. The article also describes the substantial impact of lupus on employment outcomes for individuals living with the condition. The author also reviews major signs and symptoms of disease and their impact on employment. Findings from this research can be used to identify various accommodations and strategies for individuals to prevent flare-ups. The paper presents innovative strategies that include early interventions and how employers andco-workers can provide helpful support that includes job accommodations to individuals with lupus.

Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Cutaneous Lupus Erythematosus: A Population-Based Cohort Study.

PubMed

Singh, Abha G; Crowson, Cynthia S; Singh, Siddharth; Denis, Mark; Davis, P; Maradit-Kremers, Hilal; Matteson, Eric L; Chowdhary, Vaidehi R

2016-11-01

It is unclear whether isolated cutaneous lupus erythematosus (CLE) affects cardiovascular risk. We estimated the cumulative incidence and mortality of cardiovascular diseases in a population-based CLE cohort and compared the risk with a matched non-CLE cohort. All incident cases of CLE in Olmsted County, Minnesota, between 1965 and 2005 were followed until December 2013. The cumulative incidence of cerebrovascular accidents (CVAs [including stroke and transient ischemic attack]), ischemic heart disease (IHD [including coronary artery disease, myocardial infarction, and angina pectoris]), heart failure, and peripheral arterial disease (PAD) was derived and compared to an age-, sex-, and calendar year-matched non-CLE cohort using Cox models. There were 155 patients with CLE (mean ± SD age at diagnosis 48 ± 16 years, 65% female, mean ± SD BMI 26.3 ± 7.1 kg/m 2 , 40% smokers, 9% with diabetes mellitus). During a median followup of 14.6 years, 41 CLE patients had cardiovascular events (15 patients with CVAs, 32 patients with IHD), with a 20-year cumulative incidence of 31.6%. As compared to non-CLE subjects, the risk of CVAs (smoking-adjusted hazard ratio [HR] 2.97 [95% confidence interval (95% CI) 1.13-7.78]) and PAD (HR 2.06 [95% CI 0.99-4.32]) was increased in patients with CLE, but the risk of IHD was not increased (HR 0.94 [95% CI 0.57-1.54]). There was no increase in cardiovascular mortality (HR 1.68 [95% CI 0.76-3.75]). The magnitude of risk for any cardiovascular outcome was not significantly influenced by the extent of cutaneous involvement. CLE may be associated with an increased risk of CVAs and PAD, but not IHD. Factors contributing to increased CVA risk in patients with CLE merit evaluation. © 2016, American College of Rheumatology.

Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Cutaneous Lupus Erythematosus: A Population-based Cohort Study

PubMed Central

Singh, Abha G.; Crowson, Cynthia S.; Singh, Siddharth; Davis, Mark Denis P.; Maradit-Kremers, Hilal; Matteson, Eric L.; Chowdhary, Vaidehi R.

2017-01-01

Objective It is unclear whether isolated cutaneous lupus erythematosus (CLE) modifies cardiovascular risk. We estimated the cumulative incidence and mortality of cardiovascular diseases in a population-based CLE cohort, and compared the risk with a matched non-CLE cohort. Methods All incident cases of CLE in Olmsted County, Minnesota between 1965–2005 were followed until December 2013. Cumulative incidence of cerebrovascular accidents (CVA, including stroke, transient ischemic attack), ischemic heart disease (IHD, including coronary artery disease, myocardial infarction, angina), heart failure, and peripheral arterial disease was derived and compared to an age-, sex- and calendar-year-matched non-CLE cohort using Cox models. Results There were a total of 155 patients with CLE (age at diagnosis, 48±16 years; 65% females; BMI, 26.3±7.1 kg/m2; 40% smokers, 9% with diabetes). During median follow-up of 14.6 years, 41 CLE patients developed cardiovascular events (15 patients with CVA, 32 patients with IHD), with a 20-year cumulative incidence of 31.6%. As compared to non-CLE subjects, the risk of CVAs (smoking-adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.13–7.78) and PAD (HR, 2.06; 95% CI, 0.99–4.32) was increased in patients with CLE, but risk of IHD was not increased (HR, 0.94; 95% CI, 0.57–1.54). There was no increase in cardiovascular mortality (HR, 1.68; 95% CI, 0.76–3.75). The magnitude of risk for any cardiovascular outcome was not significantly influenced by extent of cutaneous involvement. Conclusion CLE may be associated with an increased risk of CVA and PAD, but not IHD. Factors contributing to increase CVA risk in patients with CLE merit evaluation. PMID:27015109

The spectrum of renal thrombotic microangiopathy in lupus nephritis

PubMed Central

2013-01-01

Introduction Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. Methods Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. Results In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09 ± 4.64 vs. 4.75 ± 3.13 g/24h, P = 0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 μmol/l, P <0.001), higher scores of total activity indices (AI) (P <0.001), endocapillary hypercellularity (P <0.001), subendothelial hyaline deposits (P = 0.003), interstitial inflammation (P = 0.005), glomerular leukocyte infiltration (P = 0.006), total chronicity indices (CI) (P = 0.033), tubular atrophy (P = 0.004) and interstitial fibrosis (P = 0.018). Patients with renal TMA presented with poorer renal outcome (P = 0.005) compared with the non-TMA group

Lupus Foundation of America

MedlinePlus

... Store Read About Our $3.8M Commitment to Stem Cell Research. Learn More Committed to Advancing Research on Lupus ... person with lupus? Get Answers Latest News & Stories Research News | Nov. 16, 2017 Major Lupus Stem Cell Study Receives Funding $3.8 million committed by ...

Lupus nephritis: current update

PubMed Central

2011-01-01

Lupus nephritis is a major cause of morbidity and mortality in patients with systemic lupus erythematosus. The general consensus is that 60% of lupus patients will develop clinically relevant nephritis at some time in the course of their illness. Prompt recognition and treatment of renal disease is important, as early response to therapy is correlated with better outcome. The present review summarizes our current understanding of the pathogenic mechanisms underlying lupus nephritis and how the disease is currently diagnosed and treated. PMID:22078716

Testing the Predictive Validity of the Healthy Eating Index-2015 in the Multiethnic Cohort: Is the Score Associated with a Reduced Risk of All-Cause and Cause-Specific Mortality?

PubMed

Panizza, Chloe E; Shvetsov, Yurii B; Harmon, Brook E; Wilkens, Lynne R; Le Marchand, Loic; Haiman, Christopher; Reedy, Jill; Boushey, Carol J

2018-04-05

The Healthy Eating Index-2015 (HEI-2015) was created to assess conformance of dietary intake with the Dietary Guidelines for Americans (DGA) 2015-2020. We assessed the association between the HEI-2015 and mortality from all-cause, cardiovascular disease (CVD), and cancer in the Multiethnic Cohort (MEC). White, African American, Native Hawaiian, Japanese American, and Latino adults ( n > 215,000) from Hawaii and California completed a quantitative food-frequency questionnaire at study enrollment. HEI-2015 scores were divided into quintiles for men and women. Radar graphs were used to demonstrate how dietary components contributed to HEI-2015 scores. Mortality was documented over 17-22 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards models. High HEI-2015 scores were inversely associated with risk of mortality from all-cause, CVD, and cancer for men and women ( p -trend <0.0001 for all models). For men, the HRs (CIs) for all-cause, CVD, and cancer comparing the highest to the lowest quintile were 0.79 (0.76, 0.82), 0.76 (0.71, 0.82), and 0.80 (0.75, 0.87), respectively. For women, the HRs were 0.79 (0.76, 0.82), 0.75 (0.70, 0.81), and 0.84 (0.78, 0.91), respectively. These results, in a multiethnic population, demonstrate that following a diet aligned with the DGAs 2015-2020 recommendations is associated with lower risk of mortality from all-cause, CVD, and cancer.

A 12-year retrospective review of bullous systemic lupus erythematosus in cutaneous and systemic lupus erythematosus patients.

PubMed

Chanprapaph, K; Sawatwarakul, S; Vachiramon, V

2017-10-01

Objective The aim of this study was to investigate the clinical features, laboratory findings, systemic manifestations, treatment and outcome of patients with bullous systemic lupus erythematosus in a tertiary care center in Thailand. Methods We performed a retrospective review from 2002 to 2014 of all patients who fulfilled the diagnostic criteria for bullous systemic lupus erythematosus to evaluate for the clinical characteristics, extracutaneous involvement, histopathologic features, immunofluorescence pattern, serological abnormalities, internal organ involvement, treatments and outcome. Results Among 5149 patients with cutaneous lupus erythematosus and/or systemic lupus erythematosus, 15 developed vesiculobullous lesions. Ten patients had validation of the diagnosis of bullous systemic lupus erythematosus, accounting for 0.19%. Bullous systemic lupus erythematosus occurred after the diagnosis of systemic lupus erythematosus in six patients with a median onset of 2.5 months (0-89). Four out of 10 patients developed bullous systemic lupus erythematosus simultaneously with systemic lupus erythematosus. Hematologic abnormalities and renal involvement were found in 100% and 90%, respectively. Polyarthritis (40%) and serositis (40%) were less frequently seen. Systemic corticosteroids, immunosuppressants, antimalarials and dapsone offered resolution of cutaneous lesions. Conclusion Bullous systemic lupus erythematosus is an uncommon presentation of systemic lupus erythematosus. Blistering can occur following or simultaneously with established systemic lupus erythematosus. We propose that clinicians should carefully search for systemic involvement, especially hematologic and renal impairment, in patients presenting with bullous systemic lupus erythematosus.

Predictive risk factors for failure to induction therapy of lupus nephritis in a cohort of Colombian patients.

PubMed

Pinto Peñaranda, Luis Fernando; Castro Mercado, Inis Lizeth; Duque Caballero, Vladimir; Márquez Hernández, Javier Darío; Velásquez Franco, Carlos Jaime

2014-01-01

To determine the predictors of failure to obtain remission after induction therapy for proliferative lupus nephritis in a group of northwestern Colombian patients. A retrospective study was conducted. We included patients with systemic lupus erythematosus according to the American College of Rheumatology criteria who had nephritis confirmed by renal biopsy. We followed 84 patients: 88.1% female, and 11.9% male. The mean age at diagnosis of systemic lupus erythematosus was 27.5±11.8 years (9-70). The average time between diagnosis of systemic lupus erythematosus and proliferative nephritis onset was 13.6 months (0-168). Histopathologic type: iv (78.57%), iii (15.47%), iii-iv/v (5.96%). Activity index: 6.7±4.6. Chronicity index: 2±2.7. 24-hour proteinuria (mg): 6,164 (130-18,100). Baseline creatinine: 1.14 mg/dL (0.43-7.4). Induction therapy: Steroids (100%), cyclophosphamide (76.2%) and mycophenolate mofetil (23.8%). At six months, 56% of individuals failed to achieve partial or complete remission. Predictors of failure to induction therapy were, in accordance with the bivariate analysis (OR; 95%CI): creatinine level more than 1.2mg/dL (10.8; 3.18-36.84; P<.005), nephrotic range proteinuria (11.9; 3.09-45.8; P<.001), and an activity index above 8 (5.04; 1.7-14.3; P<.001). In the multivariate analysis, only baseline creatinine higher than 1.2mg/dL (10.92; 2.65-45.02; P=.001), and nephrotic range proteinuria (9.81; 1.85-52.04; P=.007) were significant. A significant percentage of Colombian patients fail to achieve remission of proliferative lupus nephritis after six months of treatment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Renal biopsy pathology in a cohort of patients from southwest Sydney with clinically diagnosed systemic lupus erythematosus

PubMed Central

Yong, Jim LC; Killingsworth, Murray C; Lai, Ken

2013-01-01

Purpose The pathological manifestations in the kidneys in systemic lupus erythematosus (SLE) are commonly known as lupus nephritis. We have studied the pathological changes in renal biopsies from 59 cases of clinically diagnosed SLE obtained over a 15-year period from a racially diverse population in the Sydney metropolitan area. Our aim was to see if there was any regional variation in the morphological changes. Methods Renal biopsy changes were assessed by routine light, immunofluorescence, and electron microscopy. We used the modified 1974 World Health Organization classification of lupus nephritis to classify cases into six classes. Disease severity was assessed by age, sex, and across racial groups, including Caucasian, Asian, Middle Eastern, Mediterranean, Indian subcontinental, South American, and Pacific Islander. Results Our analysis showed that cases of lupus nephritis contributed 5.4% of our total renal biopsies examined over a 15-year period. The overall incidence of biopsy-proven cases was 0.49 per 100,000 per year. The ages of our patients ranged from 10 to 79 years, with most below 50 years of age. A female to male ratio was determined to be 4.4:1. There was no relationship to ethnicity, nor was there a relationship between any of these parameters and the class or severity of disease. Conclusion Renal biopsy with multimodal morphological and immunohistochemical analysis remains the gold standard for diagnosis and determination of the level of disease in lupus nephritis. Based on this approach we have identified an incidence rate for southwest Sydney that is slightly higher but comparable to that found in a similar study from the United Kingdom. We also found that there was no relationship between sex, race, or age and severity of disease. PMID:23431084

The effects of previous hysterectomy on lupus.

PubMed

Namjou, B; Scofield, R H; Kelly, J A; Goodmon, E l; Aberle, T; Bruner, G R; Harley, J B

2009-10-01

Hysterectomy is one of the most common surgical procedures performed in United States, and currently, one in three women in United States has had a hysterectomy by the age of 60 years. Systemic lupus erythematosus (SLE) is a common autoimmune disease and especially targets women of childbearing age at least 10 times higher than men, which reflects the major role of female sex hormones. In this retrospective study, we evaluate the potential effects of previous hysterectomy in our lupus cohort. Data collected from study subject questionnaires were obtained from the Lupus Family Registry and Repository (LFRR) at the Oklahoma Medical Research Foundation. Hysterectomy data were available from 3389 subjects. SLE patients with a positive history of hysterectomy have been selected and compared with matched lupus patients with a negative history of hysterectomy and healthy controls. Association analyses were performed, and the P values and adjusted odds ratios (ORs) were calculated. SLE patients with a negative history of hysterectomy more likely had kidney nephritis or positive anti-dsDNA than age-matched SLE patients with a history of hysterectomy before disease onset. This effect was independent of ethnicity with an OR of 6.66 (95% CI = 3.09-14.38, P = 1.00 x 10(-8)) in European patients and 2.74 (95% CI = 1.43-5.25, P = 0.001) in African-Americans. SLE patients with a positive history of hysterectomy before disease onset also had a later age of disease onset (P = 0.0001) after adjustment for age and race. Our findings support the notion that the influence of female sex hormones in SLE and various clinical findings are tremendous and that surgical menopause such as this could significantly affect the outcome of disease and clinical manifestations.

Lung and gastrointestinal complications are leading causes of death in SCORE, a multi-ethnic Singapore systemic sclerosis cohort.

PubMed

Santosa, A; Tan, C S; Teng, G G; Fong, W; Lim, A; Law, W G; Chan, G; Ng, S C; Low, Ahl

2016-11-01

To assess contemporary outcomes and predictors of mortality in the well-characterized multi-ethnic systemic sclerosis cohort Singapore (SCORE). From 2008, patients diagnosed with systemic sclerosis (SSc) fulfilling the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) or Very Early Diagnosis of Systemic Sclerosis (VEDOSS) criteria were recruited from three major tertiary rheumatology centres in Singapore. Mortality was verified with the Singapore National Registry of Deaths and in-hospital cause of death was determined by two independent reviewers, up to 10 December 2013. A Cox proportional hazard (PH) regression analysis was used to examine the association between demographic and clinical indices and mortality, controlling for age and race. Of the 349 patients (86.8% female; 77.7% Chinese), 97.4% fulfilled the ACR/EULAR 2013 criteria. The mean age at diagnosis was 46.2 years. The prevalence of limited (lcSSc), diffuse (dcSSc) cutaneous SSc, and SSc-overlap syndromes was 34.4, 37.1, and 26.8%, respectively. Thirty-five patients died after a mean follow-up of 2.1 years (743.6 person-years). Fifty-seven per cent of deaths were attributed to SSc, with pulmonary arterial hypertension (PAH), interstitial lung disease (ILD), and gastrointestinal (GI) complications as the leading causes of death. Multivariate analysis (n = 275) showed that smoking [hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.5-10.6], SSc-overlap (HR 6.0, 95% CI 1.8-19.1), baseline renal involvement (HR 2.5, 95% CI 1.1-6.0), pulmonary artery systolic pressure (PASP) ≥ 40 mmHg on echocardiography (HR 5.1, 95% CI 2.2-11.7), treatment for peripheral vasculopathy (HR 2.6, 95% CI 1.1-6.5), and parenteral nutrition (HR 8.8, 95% CI 2.2-34.3) were independent predictors of mortality. PAH, ILD, and GI complications were leading causes of death in this cohort. We identified a high-risk group of patients who would benefit from closer monitoring and early intervention.

Clinical and serologic factors associated with lupus pleuritis.

PubMed

Mittoo, Shikha; Gelber, Allan C; Hitchon, Carol A; Silverman, Earl D; Pope, Janet E; Fortin, Paul R; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Gladman, Dafna D; Urowitz, Murray B; Zummer, Michel; Clarke, Ann E; Bernatsky, Sasha; Hudson, Marie; Tucker, Lori B; Petty, Ross E; Peschken, Christine A

2010-04-01

Pleuritis is a common manifestation and independent predictor of mortality in systemic lupus erythematosus (SLE). We examined the prevalence of pleuritis and factors associated with pleuritis in a multicenter Canadian SLE cohort. We studied consecutive adults satisfying the American College of Rheumatology (ACR) classification criteria for SLE who had a completed Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) score, at least 1 evaluable extractable nuclear antigen assay, and either a SLE Disease Activity Index (SLEDAI) or a SLE Activity Measure score. Pleuritis was defined as having pleuritis by satisfying the ACR criteria or the SLEDAI. Factors related to pleuritis were examined using univariate and multivariate logistic regression. In our cohort of 876 patients, 91% were women, 65% Caucasian, mean age (+/- SD) was 46.8 +/- 13.5 years, and disease duration at study entry was 12.1 +/- 9.9 years; the prevalence of pleuritis was 34% (n = 296). Notably, greater disease duration (p = 0.002), higher SDI score (p cohort. Concomitant Sm and RNP seropositivity, greater cumulative damage, longer disease duration, and younger age at SLE disease onset were related to a higher rate of SLE pleural disease.

Male-only systemic lupus.

PubMed

Aggarwal, Rachna; Namjou, Bahram; Li, Shibo; D'Souza, Anil; Tsao, Betty P; Bruner, Benjamin F; James, Judith A; Scofield, R Hal

2010-07-01

Systemic lupus erythematosus (SLE) is more common among women than men, a ratio of about 10 to 1. We undertook this study to describe familial male SLE within a large familial SLE cohort. SLE families (2 or more patients) were identified from the Lupus Multiplex Registry and Repository. Genomic DNA and blood samples were obtained using standard methods. Autoantibodies were determined by multiple methods. Medical records were abstracted for SLE clinical data. Fluorescent in situ hybridization (FISH) was performed with X and Y centromere-specific probes, and a probe specific for the Toll-like receptor 7 gene on the X chromosome. Among 523 SLE families, we found 5 families in which all the SLE patients were male. FISH found no yaa gene equivalent in these families. SLE-unaffected primary female relatives from the 5 families with only-male SLE patients had a statistically increased rate of positive antinuclear antibodies compared to SLE-unaffected female relatives in other families. White men with SLE were 5 times more likely to have an offspring with SLE than White women with SLE, but there was no difference in this likelihood among Black men. Because women in the all-male families had positive antinuclear antibodies, and men are more likely to have children with SLE, these data suggest genetic susceptibility factors that act only in men.

Prolactin and Dehydroepiandrosterone Levels in Women with Systemic Lupus Erythematosus: The Role of the Extrapituitary Prolactin Promoter Polymorphism at -1149G/T.

PubMed

Treadwell, Edward L; Wiley, Kenneth; Word, Beverly; Melchior, William; Tolleson, William H; Gopee, Neera; Hammons, George; Lyn-Cook, Beverly D

2015-01-01

Systemic lupus erythematosus (SLE) has shown an association with high levels of prolactin, low levels of dehydroepiandrosterone (DHEA), and induction of inflammatory cytokines in the serum of patients with the disease. This preliminary study examined the relevance of a -1149G/T functional single-nucleotide polymorphism (SNP) (rs1341239) in the promoter of the extrapituitary prolactin gene in a cohort of African American and European American women with lupus. Examination of this SNP revealed that the -1149TT genotype was correlated with higher levels of prolactin in serum and prolactin gene expression (p = 0.0001) in peripheral blood mononuclear cells (PBMCs). Lower levels of DHEA in serum were demonstrated in lupus patients (p = 0.001); those with the -1149TT genotype had the lowest levels of DHEA. Furthermore, a small subset of women who were on DHEA therapy and had a TT genotype showed a significant decrease in prolactin gene expression and lower disease activity scores (SLEDAI). Lupus patients, particularly African Americans, had significantly higher levels of IL-6 (p = 0.0001) and TNF-α (p = 0.042). This study suggests that the -1149TT genotype may be a risk factor for lupus and may predict who could possibly benefit from DHEA therapy; therefore, these results should be validated in a larger cohort with all ethnic groups.

Newly reported lupus and rheumatoid arthritis in relation to deployment within proximity to a documented open-air burn pit in Iraq.

PubMed

Jones, Kelly A; Smith, Besa; Granado, Nisara S; Boyko, Edward J; Gackstetter, Gary D; Ryan, Margaret A K; Phillips, Christopher J; Smith, Tyler C

2012-06-01

To assess the relationship between possible exposure to smoke from documented open-air burn pits and newly reported lupus and rheumatoid arthritis among Millennium Cohort participants who have deployed in support of operations in Iraq and Afghanistan. Prospectively assessed self-reported lupus and rheumatoid arthritis among deployers who completed both 2004-2006 and 2007-2008 questionnaires. After exclusions, more than 18,000 participants were deployed, including more than 3000 participants deployed within a 3-mile radius of a documented burn pit. After adjustment, proximity within 3 miles of a burn pit was not significantly associated with rheumatoid arthritis or lupus in general; however, one location was associated with lupus, although few cases were at this site (n = 2). Results indicate deployers potentially exposed to documented burn pits in the combined three-camp analysis were not at an elevated risk of lupus or rheumatoid arthritis.

Diet and Nutrition With Lupus

MedlinePlus

... on Twitter Facebook Pinterest Email Print Diet and nutrition with lupus Lupus Foundation of America April 19, ... newsletter Related Resources Diet and Lupus ABCs of nutrition Thinking about drinking? Read this first. Stick to ...

Living with Lupus (For Parents)

MedlinePlus

... Videos for Educators Search English Español Living With Lupus KidsHealth / For Parents / Living With Lupus What's in ... disease for both doctors and their patients. About Lupus A healthy immune system produces proteins called antibodies ...

Validation of the Framingham general cardiovascular risk score in a multiethnic Asian population: a retrospective cohort study

PubMed Central

Gray, Sarah Yu Weng; Ching, Siew Mooi; Lim, Hooi Min; Chinna, Karuthan

2015-01-01

Objective This study aims to examine the validity of the Framingham general cardiovascular disease (CVD) risk chart in a primary care setting. Design This is a 10-year retrospective cohort study. Setting A primary care clinic in a teaching hospital in Malaysia. Participants 967 patients’ records were randomly selected from patients who were attending follow-up in the clinic. Main outcome measures Baseline demographic data, history of diabetes and smoking, blood pressure (BP), and serum lipids were captured from patient records in 1998. Each patient's Framingham CVD score was computed from these parameters. All atherosclerotic CVD events occurring between 1998 and 2007 were counted. Results In 1998, mean age was 57 years with 33.8% men, 6.1% smokers, 43.3% diabetics and 59.7% hypertensive. Median BP was 140/80 mm Hg and total cholesterol 6.0 mmol/L (1.3). The predicted median Framingham general CVD risk score for the study population was 21.5% (IQR 1.2–30.0) while the actual CVD events that occurred in the 10 years was 13.1% (127/967). The median CVD points for men was 30.0, giving them a CVD risk of more than 30%; for women it is 18.5, a CVD risk of 21.5%. Our study found that the Framingham general CVD risk score to have moderate discrimination with an area under the receiver operating characteristic curve (AUC) of 0.63. It also discriminates well for Malay (AUC 0.65, p=0.01), Chinese (AUC 0.60, p=0.03), and Indians (AUC 0.65, p=0.001). There was good calibration with Hosmer-Lemeshow test χ2=3.25, p=0.78. Conclusions Taking into account that this cohort of patients were already on treatment, the Framingham General CVD Risk Prediction Score predicts fairly accurately for men and overestimates somewhat for women. In the absence of local risk prediction charts, the Framingham general CVD risk prediction chart is a reasonable alternative for use in a multiethnic group in a primary care setting. PMID:25991451

Validation of the Framingham general cardiovascular risk score in a multiethnic Asian population: a retrospective cohort study.

PubMed

Chia, Yook Chin; Gray, Sarah Yu Weng; Ching, Siew Mooi; Lim, Hooi Min; Chinna, Karuthan

2015-05-19

This study aims to examine the validity of the Framingham general cardiovascular disease (CVD) risk chart in a primary care setting. This is a 10-year retrospective cohort study. A primary care clinic in a teaching hospital in Malaysia. 967 patients' records were randomly selected from patients who were attending follow-up in the clinic. Baseline demographic data, history of diabetes and smoking, blood pressure (BP), and serum lipids were captured from patient records in 1998. Each patient's Framingham CVD score was computed from these parameters. All atherosclerotic CVD events occurring between 1998 and 2007 were counted. In 1998, mean age was 57 years with 33.8% men, 6.1% smokers, 43.3% diabetics and 59.7% hypertensive. Median BP was 140/80 mm Hg and total cholesterol 6.0 mmol/L (1.3). The predicted median Framingham general CVD risk score for the study population was 21.5% (IQR 1.2-30.0) while the actual CVD events that occurred in the 10 years was 13.1% (127/967). The median CVD points for men was 30.0, giving them a CVD risk of more than 30%; for women it is 18.5, a CVD risk of 21.5%. Our study found that the Framingham general CVD risk score to have moderate discrimination with an area under the receiver operating characteristic curve (AUC) of 0.63. It also discriminates well for Malay (AUC 0.65, p=0.01), Chinese (AUC 0.60, p=0.03), and Indians (AUC 0.65, p=0.001). There was good calibration with Hosmer-Lemeshow test χ(2)=3.25, p=0.78. Taking into account that this cohort of patients were already on treatment, the Framingham General CVD Risk Prediction Score predicts fairly accurately for men and overestimates somewhat for women. In the absence of local risk prediction charts, the Framingham general CVD risk prediction chart is a reasonable alternative for use in a multiethnic group in a primary care setting. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Cardiac Magnetic Resonance-Measured Left Atrial Volume and Function and Incident Atrial Fibrillation: Results From MESA (Multi-Ethnic Study of Atherosclerosis).

PubMed

Habibi, Mohammadali; Samiei, Sanaz; Ambale Venkatesh, Bharath; Opdahl, Anders; Helle-Valle, Thomas M; Zareian, Mytra; Almeida, Andre L C; Choi, Eui-Young; Wu, Colin; Alonso, Alvaro; Heckbert, Susan R; Bluemke, David A; Lima, João A C

2016-08-01

Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases. In a case-cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01-1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48-0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40-0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52-0.95), but not active LA emptying fraction, were associated with incident AF. Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development. © 2016 American Heart Association, Inc.

Lupus anticoagulant, disease activity and low complement in the first trimester are predictive of pregnancy loss.

PubMed

Mankee, Anil; Petri, Michelle; Magder, Laurence S

2015-01-01

Multiple factors, including proteinuria, antiphospholipid syndrome, thrombocytopenia and hypertension, are predictive of pregnancy loss in systemic lupus erythematosus (SLE). In the PROMISSE study of predictors of pregnancy loss, only a battery of lupus anticoagulant tests was predictive of a composite of adverse pregnancy outcomes. We examined the predictive value of one baseline lupus anticoagulant test (dilute Russell viper venom time) with pregnancy loss in women with SLE. From the Hopkins Lupus Cohort, there were 202 pregnancies from 175 different women after excluding twin pregnancies and pregnancies for which we did not have a first trimester assessment of lupus anticoagulant. We determined the percentage of women who had a pregnancy loss in groups defined by potential risk factors. The lupus anticoagulant was determined by dilute Russell viper venom time with appropriate mixing and confirmatory testing. Generalised estimating equations were used to calculate p values, accounting for repeated pregnancies in the same woman. The age at pregnancy was <20 years (2%), 20-29 (53%), 30-39 (41%) and >40 (3%). 55% were Caucasian and 34% African-American. Among those with lupus anticoagulant during the first trimester, 6/16 (38%) experienced a pregnancy loss compared with only 16/186 (9%) of other pregnancies (p=0.003). In addition, those with low complement or higher disease activity had a higher rate of pregnancy loss than those without (p=0.049 and 0.005, respectively). In contrast, there was no association between elevated anticardiolipin in the first trimester and pregnancy loss. The strongest predictor of pregnancy loss in SLE in the first trimester is the lupus anticoagulant. In addition, moderate disease activity by the physician global assessment and low complement measured in the first trimester were predictive of pregnancy loss. These data suggest that treatment of the lupus anticoagulant could be considered, even in the absence of history of pregnancy

Influence of Education on Disease Activity and Damage in Systemic Lupus Erythematosus: Data From the 1000 Canadian Faces of Lupus.

PubMed

George, Angela; Wong-Pak, Andrew; Peschken, Christine A; Silverman, Earl; Pineau, Christian; Smith, C Douglas; Arbillaga, Hector; Zummer, Michel; Bernatsky, Sasha; Hudson, Marie; Hitchon, Carol; Fortin, Paul R; Nevskaya, Tatiana; Pope, Janet E

2017-01-01

To determine whether socioeconomic status assessed by education is associated with disease activity and the risk of organ damage in systemic lupus erythematosus (SLE). Data from the 1000 Canadian Faces of Lupus, a multicenter database of adult SLE patients, was used to compare education as either low (did not complete high school) or high (completed high school or further) for disease activity and damage. Education was also studied as a continuous variable. The relationships between education and SLE outcomes (any organ damage defined as a Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index [SDI] score ≥1, serious organ damage [SDI score ≥3], and end-stage renal disease) were evaluated using logistic regression analyses adjusted for age, sex, race/ethnicity, and disease duration. A total of 562 SLE patients met inclusion criteria (mean age 47 years, 91% female, and mean disease duration of 10 years); 81% had high education. The low education group was twice as likely to be work disabled (30%; P < 0.0001); they had higher disease activity and reduced renal function. Linear regression analysis revealed that low education was significantly associated with higher disease activity at enrollment into the 1000 Canadian Faces of Lupus database, after adjustment for age (at entry and at diagnosis), race/ethnicity, and sex (B 1.255 + 0.507 [SE], β = 0.115, P = 0.014). In our adjusted logistic regression models we were unable to demonstrate significant associations between education and SLE damage. Results did not change when varying the education variable. In this cohort, low education was associated cross-sectionally with higher disease activity and work disability, but not damage. © 2016, American College of Rheumatology.

Low prevalence of Pneumocystis pneumonia in hospitalized patients with systemic lupus erythematosus: review of a clinical data warehouse.

PubMed

Kapoor, T M; Mahadeshwar, P; Nguyen, S; Li, J; Kapoor, S; Bathon, J; Giles, J; Askanase, A

2017-12-01

Objective In the era of powerful immunosuppression, opportunistic infections are an increasing concern in systemic lupus erythematosus. One of the best-studied opportunistic infections is Pneumocystis pneumonia; however, the prevalence of Pneumocystis pneumonia in systemic lupus erythematosus is not clearly defined. This study evaluates the prevalence of Pneumocystis pneumonia in hospitalized systemic lupus erythematosus patients, with a focus on validating the Pneumocystis pneumonia and systemic lupus erythematosus diagnoses with clinical information. Methods This retrospective cohort study evaluates the prevalence of Pneumocystis pneumonia in all systemic lupus erythematosus patients treated at Columbia University Medical Center-New York Presbyterian Hospital between January 2000 and September 2014, using electronic medical record data. Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and patients with renal transplants (including both early and late post-transplant patients) represented immunocompromised control groups. Patients with systemic lupus erythematosus, Pneumocystis pneumonia, HIV/AIDS, or renal transplant were identified using diagnostic codes from the International Classification of Diseases, Ninth Revision (ICD-9). Results Out of 2013 hospitalized systemic lupus erythematosus patients, nine had presumed Pneumocystis pneumonia, yielding a low prevalence of Pneumocystis pneumonia in systemic lupus erythematosus of 0.45%. Three of the nine Pneumocystis pneumonia cases were patients with concomitant systemic lupus erythematosus and HIV/AIDS. Only one of these nine cases was histologically confirmed as Pneumocystis pneumonia, in a patient with concomitant systemic lupus erythematosus and HIV/AIDS and a CD4 count of 13 cells/mm 3 . The prevalence of Pneumocystis pneumonia in renal transplant patients and HIV/AIDS patients was 0.61% and 5.98%, respectively. Conclusion Given the reported high rate of adverse effects

Testing the Predictive Validity of the Healthy Eating Index-2015 in the Multiethnic Cohort: Is the Score Associated with a Reduced Risk of All-Cause and Cause-Specific Mortality?

PubMed Central

Panizza, Chloe E.; Shvetsov, Yurii B.; Harmon, Brook E.; Wilkens, Lynne R.; Le Marchand, Loic; Haiman, Christopher; Reedy, Jill

2018-01-01

The Healthy Eating Index-2015 (HEI-2015) was created to assess conformance of dietary intake with the Dietary Guidelines for Americans (DGA) 2015–2020. We assessed the association between the HEI-2015 and mortality from all-cause, cardiovascular disease (CVD), and cancer in the Multiethnic Cohort (MEC). White, African American, Native Hawaiian, Japanese American, and Latino adults (n > 215,000) from Hawaii and California completed a quantitative food-frequency questionnaire at study enrollment. HEI-2015 scores were divided into quintiles for men and women. Radar graphs were used to demonstrate how dietary components contributed to HEI-2015 scores. Mortality was documented over 17–22 years of follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using Cox proportional hazards models. High HEI-2015 scores were inversely associated with risk of mortality from all-cause, CVD, and cancer for men and women (p-trend <0.0001 for all models). For men, the HRs (CIs) for all-cause, CVD, and cancer comparing the highest to the lowest quintile were 0.79 (0.76, 0.82), 0.76 (0.71, 0.82), and 0.80 (0.75, 0.87), respectively. For women, the HRs were 0.79 (0.76, 0.82), 0.75 (0.70, 0.81), and 0.84 (0.78, 0.91), respectively. These results, in a multiethnic population, demonstrate that following a diet aligned with the DGAs 2015–2020 recommendations is associated with lower risk of mortality from all-cause, CVD, and cancer. PMID:29621192

Organ damage accrual and distribution in systemic lupus erythematosus patients followed-up for more than 10 years.

PubMed

Taraborelli, M; Cavazzana, I; Martinazzi, N; Lazzaroni, M Grazia; Fredi, M; Andreoli, L; Franceschini, F; Tincani, A

2017-10-01

Objective The aim of this study was to determine the prevalence, predictors and progression of organ damage in a monocentric cohort of systemic lupus erythematosus patients with a long follow-up. Organ damage was assessed by the Systemic Lupus International Collaborating Clinics Damage Index one year after diagnosis and every five years. Disease activity was measured by the systemic lupus erythematosus disease activity index (SLEDAI)-2K at the beginning of the follow-up. Univariate and multivariable analyses were used to detect items associated with damage. A total of 511 systemic lupus erythematosus patients (92% females, 95% Caucasian), prospectively followed from 1972 to 2014, were included. Results After a mean disease duration of 16 years (SD: 9.5) and a mean follow-up of 12.9 years (SD: 8.8), 354 patients (69.3%) had accrued some damage: 49.7% developed mild/moderate damage, while 19.5% showed severe damage. Damage was evident in 40% of 511 patients one year after diagnosis, and its prevalence linearly increased over time. Longer disease duration, higher SLEDAI, severe Raynaud's, chronic alopecia and cerebral ischaemia were significantly associated with organ damage. No associations between damage and autoantibodies, including anti-dsDNA, anti-Sm or antiphospholipid antibodies, were observed. Anyway, antiphospholipid syndrome and anticardiolipin antibodies predicted the development of neuropsychiatric damage. The ocular, musculoskeletal and neuropsychiatric systems were the most frequently damaged organs, with a linear increase during follow-up. Conclusion A high rate of moderate and severe damage has been detected early in a wide cohort of young lupus patients, with a linear trend of increase over time. Disease activity and long duration of disease predict damage, while antiphospholipid antibodies play a role in determining neuropsychiatric damage.

Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases.

PubMed

Komvilaisak, Patcharee; Wisanuyotin, Suwannee; Jettrisuparb, Arunee; Wiangnon, Surapon

2017-11-01

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

Hypogammaglobulinemia in pediatric systemic lupus erythematosus.

PubMed

Lim, E; Tao, Y; White, A J; French, A R; Cooper, M A

2013-11-01

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease typically associated with elevated serum immunoglobulin G (IgG). Hypogammaglobulinemia in SLE patients has been attributed to immunosuppressive treatment or a transient effect associated with nephrotic syndrome. We retrospectively reviewed pediatric SLE patients from a single institution to identify patients with hypogammaglobulinemia and risk factors for hypogammaglobulinemia. A total of 116 pediatric SLE cases from 1997 to 2011 were reviewed and patients with hypogammaglobulinemia (IgG < 500 mg/dl) were identified. The two cohorts were evaluated for association with age, sex, presence of lupus nephritis at SLE diagnosis, disease activity at diagnosis, initial IgG level, and drug treatment. Eighty-six patients were included in our study, with a median age of 15 years and a median follow-up of 39.5 months. Seven percent (six of 86) of patients had hypogammaglobulinemia with a median onset of 27 months (0-72 months) after SLE diagnosis. Significant associations were noted for white race (p value 0.029), male sex (p value 0.009), and the presence of lupus nephritis at SLE diagnosis (p value 0.004). Use of immunosuppressive treatment did not show a statistical association with hypogammaglobulinemia, although two of the patients with hypogammaglobulinemia did receive rituximab. Most patients with hypogammaglobulinemia received intravenous immunoglobulin (IVIG) replacement therapy because of infections and/or concern for infection. Measurement of immunoglobulin levels during treatment in SLE could help identify patients with hypogammaglobulinemia who might require more aggressive follow-up to monitor for increased risk of infection and need for IVIG treatment. A prospective study is needed to validate associated risk factors identified in this study.

Self-reported Ethnicity, Genetic Structure and the Impact of Population Stratification in a Multiethnic Study

PubMed Central

Wang, Hansong; Haiman, Christopher A.; Kolonel, Laurence N.; Henderson, Brian E.; Wilkens, Lynne R.; Le Marchand, Loïc; Stram, Daniel O.

2011-01-01

It is well-known that population substructure may lead to confounding in case-control association studies. Here, we examined genetic structure in a large racially and ethnically diverse sample consisting of 5 ethnic groups of the Multiethnic Cohort study (African Americans, Japanese Americans, Latinos, European Americans and Native Hawaiians) using 2,509 SNPs distributed across the genome. Principal component analysis on 6,213 study participants, 18 Native Americans and 11 HapMap III populations revealed 4 important principal components (PCs): the first two separated Asians, Europeans and Africans, and the third and fourth corresponded to Native American and Native Hawaiian (Polynesian) ancestry, respectively. Individual ethnic composition derived from self-reported parental information matched well to genetic ancestry for Japanese and European Americans. STRUCTURE-estimated individual ancestral proportions for African Americans and Latinos are consistent with previous reports. We quantified the East Asian (mean 27%), European (mean 27%) and Polynesian (mean 46%) ancestral proportions for the first time, to our knowledge, for Native Hawaiians. Simulations based on realistic settings of case-control studies nested in the Multiethnic Cohort found that the effect of population stratification was modest and readily corrected by adjusting for race/ethnicity or by adjusting for top PCs derived from all SNPs or from ancestry informative markers; the power of these approaches was similar when averaged across causal variants simulated based on allele frequencies of the 2,509 genotyped markers. The bias may be large in case-only analysis of gene by gene interactions but it can be corrected by top PCs derived from all SNPs. PMID:20499252

Visual Impairment in White, Chinese, Black, and Hispanic Participants from the Multi-Ethnic Study of Atherosclerosis Cohort.

PubMed

Fisher, Diana E; Shrager, Sandi; Shea, Steven J; Burke, Gregory L; Klein, Ronald; Wong, Tien Y; Klein, Barbara E; Cotch, Mary Frances

2015-01-01

To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Visual acuity data were obtained from 6134 participants, aged 46-87 years at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States. Visual impairment was defined as presenting visual acuity 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group. Among all participants, 6.6% (n = 421) had visual impairment, including 5.6% of men (n = 178) and 7.5% of women (n = 243). Prevalence of impairment ranged from 4.2% (n = 52) and 6.0% (n = 77) in white men and women, respectively, to 7.6% (n = 37) and 11.6% (n = 44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction, and not unexpectedly, a lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors. Even in the U.S. where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges.

Visual Impairment in White, Chinese, Black and Hispanic Participants from the Multi-Ethnic Study of Atherosclerosis Cohort

PubMed Central

Fisher, Diana E.; Shrager, Sandi; Shea, Steven J.; Burke, Gregory L.; Klein, Ronald; Wong, Tien Y.; Klein, Barbara E; Cotch, Mary Frances

2016-01-01

Purpose To describe the prevalence of visual impairment and examine its association with demographic, socioeconomic, and health characteristics in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Methods Visual acuity data was obtained from 6134 participants, aged 46 to 87 years old at time of examination between 2002 and 2004 (mean age 64 years, 47.6% male), from six communities in the United States (U.S.). Visual impairment was defined as a presenting visual acuity of 20/50 or worse in the better-seeing eye. Risk factors were included in multivariable logistic regression models to determine their impact on visual impairment for men and women in each racial/ethnic group. Results Among all participants, 6.6% (N=421) had visual impairment, including 5.6% (N=178) of men and 7.5% (N=243) of women. Prevalence of impairment ranged from 4.2% (N=52) and 6.0% (N=77) in White men and women, respectively, to 7.6% (N=37) and 11.6% (N=44) in Chinese men and women, respectively. Older age was significantly associated with visual impairment in both men and women, particularly in those with lower socioeconomic status, but the effects of increasing age were more pronounced in men. Two-thirds of participants already wore distance correction and not unexpectedly, lower prevalence of visual impairment was seen in this group; however, 2.4% of men and 3.5% of women with current distance correction had correctable visual impairment, most notably among seniors. Conclusion Even in the United States where prevalence of refractive correction is high, both visual impairment and uncorrected refractive error represent current public health challenges. PMID:26395659

Association between maternal haemoglobin and stillbirth: a cohort study among a multi-ethnic population in England.

PubMed

Nair, Manisha; Churchill, David; Robinson, Susan; Nelson-Piercy, Cathy; Stanworth, Simon J; Knight, Marian

2017-12-01

The study objectives were to examine the association of maternal haemoglobin with stillbirth and perinatal death in a multi-ethnic population in England. We conducted a retrospective cohort analysis using anonymised maternity data from 14 001 women with singleton pregnancies ≥24 weeks' gestation giving birth between 2013 and 2015 in two hospitals - the Royal Wolverhampton NHS Trust and Guy's and St Thomas' NHS Foundation Trust. Multivariable logistic regression analyses were undertaken to analyse the associations between maternal haemoglobin at first visit and at 28 weeks with stillbirth and perinatal death, adjusting for 11 other risk factors. Results showed that 46% of the study population had anaemia (haemoglobin <110 g/l) at some point during their pregnancy. The risk of stillbirth and perinatal death decreased linearly per unit increase in haemoglobin concentration at first visit (adjusted odds ratio [aOR] stillbirth = 0·70, 95% confidence interval [CI] 0·58-0·85, aOR perinatal death = 0·71, 95% CI 0·60-0·84) and at 28 weeks (aOR stillbirth = 0·83, 95% CI 0·66-1·04; aOR perinatal death = 0·86, 95%CI 0·67-1·12). Compared with women with haemoglobin ≥110 g/l, the risk of stillbirth and perinatal death was five- and three-fold higher in women with moderate-severe anaemia (haemoglobin <100 g/l) at first visit and 28 weeks, respectively. These findings have clinical and public health importance. © 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Improving Global Vascular Risk Prediction with Behavioral and Anthropometric Factors: The Multi-ethnic Northern Manhattan Cohort Study

PubMed Central

Sacco, Ralph L.; Khatri, Minesh; Rundek, Tatjana; Xu, Qiang; Gardener, Hannah; Boden-Albala, Bernadette; Di Tullio, Marco R.; Homma, Shunichi; Elkind, Mitchell SV; Paik, Myunghee C

2010-01-01

Objective To improve global vascular risk prediction with behavioral and anthropometric factors. Background Few cardiovascular risk models are designed to predict the global vascular risk of MI, stroke, or vascular death in multi-ethnic individuals, and existing schemes do not fully include behavioral risk factors. Methods A randomly-derived, population-based, prospective cohort of 2737 community participants free of stroke and coronary artery disease were followed annually for a median of 9.0 years in the Northern Manhattan Study (mean age 69 years; 63.2% women; 52.7% Hispanic, 24.9% African-American, 19.9% white). A global vascular risk score (GVRS) predictive of stroke, myocardial infarction, or vascular death was developed by adding variables to the traditional Framingham cardiovascular variables based on the likelihood ratio criterion. Model utility was assessed through receiver operating characteristics, calibration, and effect on reclassification of subjects. Results Variables which significantly added to the traditional Framingham profile included waist circumference, alcohol consumption, and physical activity. Continuous measures for blood pressure and fasting blood sugar were used instead of hypertension and diabetes. Ten -year event-free probabilities were 0.95 for the first quartile of GVRS, 0.89 for the second quartile, 0.79 for the third quartile, and 0.56 for the fourth quartile. The addition of behavioral factors in our model improved prediction of 10 -year event rates compared to a model restricted to the traditional variables. Conclusion A global vascular risk score that combines both traditional, behavioral, and anthropometric risk factors, uses continuous variables for physiological parameters, and is applicable to non-white subjects could improve primary prevention strategies. PMID:19958966

Predictors of kidney biopsy complication among patients with systemic lupus erythematosus.

PubMed

Chen, T K; Estrella, M M; Fine, D M

2012-07-01

Kidney biopsy is essential for the diagnosis and management of lupus nephritis. The risk of bleeding complication, however, is not defined in the systemic lupus erythematosus population. A retrospective cohort study was conducted to determine predictors of major and minor complications among patients with systemic lupus erythematosus undergoing percutaneous ultrasound-guided kidney biopsy. Major complications included bleeding necessitating intervention, hypotension requiring vasopressors or higher level of care or death. Minor complications included moderate or large (≥ 4 cm in largest diameter) perinephric hematoma, gross hematuria or voiding difficulties. All patients were observed for at least 23 h post-procedure. The overall incidence of bleeding was 10.5% (2.7% major, 7.8% minor). Adjusted logistic regression showed that for every 10,000 cells/mm(3) decrease in platelet count, risk for major and any complication increased by 27% (odds ratio 1.27; 95% confidence intervals 1.06-1.51; p = 0.01) and 8% (odds ratio 1.08; 95% confidence intervals 1.02-1.15; p = 0.01), respectively. Patients with a platelet count <150,000 cells/mm(3) were 30 times more likely to experience a major complication (p = 0.002). Other candidate predictors, including steroid exposure, kidney function, hematocrit and histopathology, were not significant. Kidney biopsies are well tolerated in patients with systemic lupus erythematosus. However, patients with pre-biopsy platelet counts <150,000 cells/mm(3) are at markedly increased risk for a major bleeding complication.

Incidence of cervical human papillomavirus infection in systemic lupus erythematosus women.

PubMed

Mendoza-Pinto, C; García-Carrasco, M; Vallejo-Ruiz, V; Méndez-Martínez, S; Taboada-Cole, A; Etchegaray-Morales, I; Muñóz-Guarneros, M; Reyes-Leyva, J; López-Colombo, A

2017-08-01

Objectives Our objective was to study the incidence, persistence and clearance of human papillomavirus infection in systemic lupus erythematosus women and assess risk factors for persistence of human papillomavirus infection. Methods We carried out a prospective, observational cohort study of 127 systemic lupus erythematosus women. Patients were evaluated at baseline and at three years. Traditional and systemic lupus erythematosus women-related disease risk factors were collected. Gynaecological evaluations and cervical cytology screening were made. Human papillomavirus detection and genotyping were made by polymerase chain reaction and linear array. Results The cumulative prevalence of human papillomavirus infection increased from 22.8% at baseline to 33.8% at three years; p = < 0.001: 20.1% of patients experienced 43 incident infections. The risk of any human papillomavirus infection was 10.1 per 1000 patient-months. At three years, 47 (88.6%) prevalent infections were cleared. Independent risk factors associated with incident human papillomavirus infection included more lifetime sexual partners (odds ratio = 1.8, 95% confidence interval = 1.11-3.0) and cumulative cyclophosphamide dose (odds ratio = 3.9, 95% confidence interval = 1.2-12.8). Conclusions In systemic lupus erythematosus women, the cumulative prevalence of human papillomavirus infection, including high risk-human papillomavirus and multiple human papillomavirus infections, may increase over time. Most persistent infections were low risk-human papillomavirus. The number of lifetime sexual partners and the cumulative cyclophosphamide dose were independently associated with incident human papillomavirus infection.

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study

PubMed Central

Park, Song-Yi; Wilkens, Lynne R.; Kolonel, Laurence N.; Henderson, Brian E.; Le Marchand, Loïc

2017-01-01

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re-examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow-up period of 16 years. In multivariable-adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61–0.89 for highest vs. lowest quintile, ptrend = 0.0020 in men and HR = 0.76, 95% CI: 0.62–0.91, ptrend = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74–0.89) compared to MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59–0.95, ptrend =0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (ptrend = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer. PMID:27137137

Determinants of Health-Related Quality of Life (HRQoL) in the Multiethnic Singapore Population - A National Cohort Study.

PubMed

Leow, Melvin Khee-Shing; Griva, Konstadina; Choo, Robin; Wee, Hwee-Lin; Thumboo, Julian; Tai, E Shyong; Newman, Stanton

2013-01-01

HRQoL is an important outcome to guide and promote healthcare. Clinical and socioeconomic factors may influence HRQoL according to ethnicity. A multiethnic cross-sectional national cohort (N = 7198) of the Singapore general population consisting of Chinese (N = 4873), Malay (N = 1167) and Indian (N = 1158) adults were evaluated using measures of HRQoL (SF-36 version 2), family functioning, health behaviours and clinical/laboratory assessments. Multiple regression analyses were performed to identify determinants of physical and mental HRQoL in the overall population and their potential differential effects by ethnicity. No a priori hypotheses were formulated so all interaction effects were explored. HRQoL levels differed between ethnic groups. Chinese respondents had higher physical HRQoL (PCS) than Indian and Malay participants (p<0.001) whereas mental HRQoL (MCS) was higher in Malay relative to Chinese participants (p<0.001). Regressions models explained 17.1% and 14.6% of variance in PCS and MCS respectively with comorbid burden, income and employment being associated with lower HRQoL. Age and family were associated only with MCS. The effects of gender, stroke and musculoskeletal conditions on PCS varied by ethnicity, suggesting non-uniform patterns of association for Chinese, Malay and Indian individuals. Differences in HRQoL levels and determinants of HRQoL among ethnic groups underscore the need to better or differentially target population segments to promote well-being. More work is needed to explore HRQoL and wellness in relation to ethnicity.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

PubMed

Lythgoe, H; Morgan, T; Heaf, E; Lloyd, O; Al-Abadi, E; Armon, K; Bailey, K; Davidson, J; Friswell, M; Gardner-Medwin, J; Haslam, K; Ioannou, Y; Leahy, A; Leone, V; Pilkington, C; Rangaraj, S; Riley, P; Tizard, E J; Wilkinson, N; Beresford, M W

2017-10-01

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients' classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

Myelopathy in systemic lupus erythematosus: clinical, laboratory, radiological and progression findings in a cohort of 1,193 patients.

PubMed

Costallat, Beatriz Lavras; Ferreira, Daniel Miranda; Costallat, Lilian Tereza Lavras; Appenzeller, Simone

2016-01-01

To describe clinical, laboratory, radiological and progression characteristics of myelopathy in systemic lupus erythematosus (SLE). A retrospective analysis was performed on a cohort of 1193 patients with SLE (ACR criteria) in order to identify patients with myelopathy (neuropsychiatric ACR). Disease activity was assessed by the SLE activity index (SLEDAI) on the date of the event and functional capacity was assessed by the Expanded Disability Status Scale (EDSS) at the last visit. We identified 14 (1.2%) patients with myelopathy. All were women with a mean age of 30±11.5 years. Myelopathy occurred at the diagnosis of SLE in four (28%) patients; and nine (64%) patients had another type of neuropsychiatric manifestation associated. Neurological recurrence was observed in one (7%) patient. Disease activity was observed in 2 (14%) patients. Cerebrospinal fluid presented pleocytosis on 7 (53%) patients; antiphospholipid antibodies were positive in 5 (45%). Magnetic resonance imaging (MRI) showed T2 hyperintensity with a predominance of longitudinal involvement in 6 (86%) patients. Most were treated with intravenous corticosteroids and cyclophosphamide. No patient had full recovery and four (36%) had high EDSS scores. Three (21%) patients died from sepsis early in the course of their myelopathy, during or after immunosuppressive therapy. Myelopathy occurred in 14 (1.2%) of the patients in our cohort and this may be the first manifestation of the disease occurring independently of systemic disease activity. Although rare, myelopathy shows great morbidity and mortality, can be recurrent and MRI is critical for diagnosis. Copyright © 2016. Published by Elsevier Editora Ltda.

Patent foramen ovale and the risk of ischemic stroke in a multiethnic population.

PubMed

Di Tullio, Marco R; Sacco, Ralph L; Sciacca, Robert R; Jin, Zhezhen; Homma, Shunichi

2007-02-20

We sought to assess the risk of ischemic stroke from a patent foramen ovale (PFO) in the multiethnic prospective cohort of northern Manhattan. Patent foramen ovale has been associated with increased risk of ischemic stroke, mainly in case-control studies. The actual PFO-related stroke risk in the general population is unclear. The presence of PFO was assessed at baseline by using transthoracic 2-dimensional echocardiography with contrast injection in 1,100 stroke-free subjects older than 39 years of age (mean age 68.7 +/- 10.0 years) from the Northern Manhattan Study (NOMAS). The presence of atrial septal aneurysm (ASA) also was recorded. Subjects were followed annually for outcomes. We assessed PFO/ASA-related stroke risk after adjusting for established stroke risk factors. We detected PFO in 164 subjects (14.9%); ASA was present in 27 subjects (2.5%) and associated with PFO in 19 subjects. During a mean follow-up of 79.7 +/- 28.0 months, an ischemic stroke occurred in 68 subjects (6.2%). After adjustment for demographics and risk factors, PFO was not found to be significantly associated with stroke (hazard ratio 1.64, 95% confidence interval [CI] 0.87 to 3.09). The same trend was observed in all age, gender, and race-ethnic subgroups. The coexistence of PFO and ASA did not increase the stroke risk (adjusted hazard ratio 1.25, 95% CI 0.17 to 9.24). Isolated ASA was associated with elevated stroke incidence (2 of 8, or 25%; adjusted hazard ratio 3.66, 95% CI 0.88 to 15.30). Patent foramen ovale, alone or together with ASA, was not associated with an increased stroke risk in this multiethnic cohort. The independent role of ASA needs further assessment in appositely designed and powered studies.

Genetics Home Reference: systemic lupus erythematosus

MedlinePlus

... Twitter Home Health Conditions Systemic lupus erythematosus Systemic lupus erythematosus Printable PDF Open All Close All Enable ... to view the expand/collapse boxes. Description Systemic lupus erythematosus (SLE) is a chronic disease that causes ...

Autoantibodies as Biomarkers for the Prediction of Neuropsychiatric Events in Systemic Lupus Erythematosus

PubMed Central

Hanly, J G; Urowitz, M B; Su, L; Bae, S-C; Gordon, C; Sanchez-Guerrero, J; Clarke, A; Bernatsky, S; Vasudevan, A; Isenberg, D; Rahman, A; Wallace, D J; Fortin, P R; Gladman, D; Dooley, M A; Bruce, I; Steinsson, K; Khamashta, M; Manzi, S; Ramsey-Goldman, R; Sturfelt, G; Nived, O; van Vollenhoven, R; Ramos-Casals, M; Aranow, C; Mackay, M; Kalunian, K; Alarcón, G S; Fessler, B J; Ruiz-Irastorza, G; Petri, M; Lim, S; Kamen, D; Peschken, C; Farewell, V; Thompson, K; Theriault, C; Merrill, J T

2015-01-01

Objective Neuropsychiatric (NP) events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. We examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrollment predicted subsequent NP events. Methods Patients with recent SLE diagnosis were assessed prospectively for up to 10 years for NP events using ACR case definitions. Decision rules of graded stringency determined whether NP events were attributable to SLE. Associations between the first NP event and baseline autoantibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrollment was 5.4±4.2 months, followup was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed ≥1 NP event (total 917 events). NP events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrollment 21.9% of patients had lupus anticoagulant, 13.4% anticardiolipin, 15.1% anti-β2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. Lupus anticoagulant at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (Hazard ratio, HR 2.54 (95% CI: 1.08–5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR: 3.92 (95% CI:1.23–12.5); p=0.02). Other autoantibodies did not predict NP events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, lupus anticoagulant and anti-ribosomal P antibodies are associated with an increased future risk for intracranial thrombosis and lupus psychosis respectively PMID:21893582

Incidence of Systemic Lupus Erythematosus in a Population Based Cohort using Revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinic Classification Criteria

PubMed Central

Ungprasert, Patompong; Sagar, Vinay; Crowson, Cynthia S.; Amin, Shreyasee; Makol, Ashima; Ernste, Floranne C.; Osborn, Thomas G.; Moder, Kevin G.; Niewold, Timothy B.; Maradit-Kremers, Hilal; Ramsey-Goldman, Rosalind; Chowdhary, Vaidehi R.

2016-01-01

In 2012, the Systemic Lupus International Collaborating Clinic (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We utilized the resource of the Rochetser Epidemiology Project to identify incident cases of SLE in Olmsted County, Minnesota from 1993-2005 who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p=0.04). The median duration from the appearance of first criteria to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria. PMID:27365370

Incidence of systemic lupus erythematosus in a population-based cohort using revised 1997 American College of Rheumatology and the 2012 Systemic Lupus International Collaborating Clinics classification criteria.

PubMed

Ungprasert, P; Sagar, V; Crowson, C S; Amin, S; Makol, A; Ernste, F C; Osborn, T G; Moder, K G; Niewold, T B; Maradit-Kremers, H; Ramsey-Goldman, R; Chowdhary, V R

2017-03-01

In 2012, the Systemic Lupus International Collaborating Clinics (SLICC) group published a new set of classification criteria for systemic lupus erythematosus (SLE). Studies applying these criteria to real-life scenarios have found either equal or greater sensitivity and equal or lower specificity to the 1997 ACR classification criteria (ACR 97). Nonetheless, there are no studies that have used the SLICC 12 criteria to investigate the incidence of lupus. We used the resource of the Rochester Epidemiology Project to identify incident SLE patients in Olmsted County, Minnesota, from 1993 to 2005, who fulfilled the ACR 97 or SLICC 12 criteria. A total of 58 patients met criteria by SLICC 12 and 44 patients met criteria by ACR 97. The adjusted incidence of 4.9 per 100,000 person-years by SLICC 12 was higher than that by ACR 97 (3.7 per 100,000 person-years, p = 0.04). The median duration from the appearance of first criterion to fulfillment of the criteria was shorter for the SLICC 12 than for ACR 97 (3.9 months vs 8.1 months). The higher incidence by SLICC 12 criteria came primarily from the ability to classify patients with renal-limited disease, the expansion of the immunologic criteria and the expansion of neurologic criteria.

Breastfeeding in mothers with systemic lupus erythematosus.

PubMed

Noviani, M; Wasserman, S; Clowse, M E B

2016-08-01

Breastfeeding is known to improve the well-being of a mother and her infant, and about half of all new mothers breastfeed, but it is unknown how breastfeeding is pursued in systemic lupus erythematosus (SLE; lupus) patients. We sought to determine the rate of breastfeeding and the factors influencing this among women with lupus. In addition, we reassessed the current safety data in lactation of lupus medications. Data were collected from lupus patients enrolled in a prospective registry who fulfilled the 2012 SLICC criteria, had a live birth, and for whom postpartum breastfeeding status was known. Data included physician assessments of lupus activity and medications, breastfeeding intentions during pregnancy and practice following pregnancy. The safety of medications in breastfed infants was assessed through a comprehensive review of LactMed, a national database about medications in lactation. A total of 51 pregnancies in 84 women with lupus were included in the study. Half of the lupus patients (n = 25, 49%) chose to breastfeed. The rate of breastfeeding was not significantly affected by socioeconomic factors. In contrast, low postpartum lupus activity, term delivery, and a plan to breastfeed early in pregnancy were significantly associated with breastfeeding in lupus patients. In reviewing the most up-to-date data, the majority of lupus medications appear to have very minimal transfer into breast milk and are likely compatible with breastfeeding. Half of women with lupus breastfed and most desire to breastfeed. Hydroxychloroquine, azathioprine, methotrexate, and prednisone have very limited transfer into breast milk and may be continued while breastfeeding. © The Author(s) 2016.

Quality of data in multiethnic health surveys.

PubMed Central

Pasick, R. J.; Stewart, S. L.; Bird, J. A.; D'Onofrio, C. N.

2001-01-01

OBJECTIVE: There has been insufficient research on the influence of ethno-cultural and language differences in public health surveys. Using data from three independent studies, the authors examine methods to assess data quality and to identify causes of problematic survey questions. METHODS: Qualitative and quantitative methods were used in this exploratory study, including secondary analyses of data from three baseline surveys (conducted in English, Spanish, Cantonese, Mandarin, and Vietnamese). Collection of additional data included interviews with investigators and interviewers; observations of item development; focus groups; think-aloud interviews; a test-retest assessment survey; and a pilot test of alternatively worded questions. RESULTS: The authors identify underlying causes for the 12 most problematic variables in three multiethnic surveys and describe them in terms of ethnic differences in reliability, validity, and cognitive processes (interpretation, memory retrieval, judgment formation, and response editing), and differences with regard to cultural appropriateness and translation problems. CONCLUSIONS: Multiple complex elements affect measurement in a multiethnic survey, many of which are neither readily observed nor understood through standard tests of data quality. Multiethnic survey questions are best evaluated using a variety of quantitative and qualitative methods that reveal different types and causes of problems. PMID:11889288

The chronic damage in systemic lupus erythematosus is driven by flares, glucocorticoids and antiphospholipid antibodies: results from a monocentric cohort.

PubMed

Conti, F; Ceccarelli, F; Perricone, C; Leccese, I; Massaro, L; Pacucci, V A; Truglia, S; Miranda, F; Spinelli, F R; Alessandri, C; Valesini, G

2016-06-01

Literature data suggest a significantly higher mortality in patients affected by systemic lupus erythematosus (SLE) developing chronic damage. Therefore, damage prevention is a major goal in the management of SLE patients. In the present study, we assessed damage by means of the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI), in a large cohort of SLE patients. Additionally, we aimed at evaluating its association with demographic and clinical features as well as with disease activity and laboratory findings. We enrolled consecutive patients affected by SLE diagnosed according to the American College of Rheumatology (ACR) 1997 revised criteria. Chronic damage was determined by SDI calculated at the last examination in all patients with at least six months of follow-up. Disease activity was assessed by the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); flare was defined as an increase of SLEDAI-2K ≥ 4 compared with the previous visit. We evaluated 349 SLE patients (M/F 25/324, mean age ± SD 42.7 ± 12.4 years, mean disease duration ± SD 164.9 ± 105.2 months). Among the enrolled patients, 125 (35.8%) showed a SDI ≥ 1 (mean SDI ± SD 1.7 ± 0.9, range 0-5). The musculo-skeletal was the most frequently involved organ/system in SDI score (41/349 patients, 11.7%), with deforming/erosive arthritis in 21/349 (6.0%). The presence of chronic damage was associated with age (P < 0.001), disease duration (P < 0.001), number of flares (P = 0.02) and with the use of glucocorticoids (P = 0.02). The logistic regression analysis revealed the association between neuropsychiatric damage and antiphospholipid syndrome (P = 0.01, OR = 3.9) and between the presence of cardiovascular damage and anti-β2GPI antibodies (P = 0.01, OR 6.2). In the present study chronic damage was identified in about one third of SLE patients. The

Characteristics of pleural effusions in systemic lupus erythematosus: differential diagnosis of lupus pleuritis.

PubMed

Choi, B Y; Yoon, M J; Shin, K; Lee, Y J; Song, Y W

2015-03-01

We investigated the clinical characteristics of pleural effusion in systemic lupus erythematosus (SLE). A prospective analysis of 17 SLE patients with pleural effusion (seven lupus pleuritis, eight transudative effusions and two parapneumonic effusions) was performed. Thirty non-SLE patients with pleural effusion were recruited as controls. A pleural fluid ANA titer ≥1:160 was found in 8/17 (47.1%) SLE patients and none of the 30 non-SLE patients (p = 0.0001). Pleural fluid to serum C3 ratios were significantly lower in SLE than in non-SLE (median (minimum-maximum) 0.29 (0.03-0.43) versus 0.52 (0.26-0.73), p = 0.0002). Among SLE patients, pleural fluid ANA titers ≥1:160 were more frequently found in patients with lupus pleuritis than in those with pleural effusion from causes other than lupus itself (85.7% versus 20.0%, p = 0.0152). Serum CRP levels were significantly increased in patients with lupus pleuritis compared with SLE patients with transudative pleural effusion (2.30 (0.30-5.66) versus 0.7 (0.12-1.47) mg/dl, p = 0.0062). In conclusion, pleural fluid ANA titer and serum CRP levels are significantly increased in lupus pleuritis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Identification of a systemic lupus erythematosus susceptibility locus at 11p13 between PDHX and CD44 in a multiethnic study.

PubMed

Lessard, Christopher J; Adrianto, Indra; Kelly, Jennifer A; Kaufman, Kenneth M; Grundahl, Kiely M; Adler, Adam; Williams, Adrienne H; Gallant, Caroline J; Anaya, Juan-Manuel; Bae, Sang-Cheol; Boackle, Susan A; Brown, Elizabeth E; Chang, Deh-Ming; Criswell, Lindsey A; Edberg, Jeffrey C; Freedman, Barry I; Gregersen, Peter K; Gilkeson, Gary S; Jacob, Chaim O; James, Judith A; Kamen, Diane L; Kimberly, Robert P; Martin, Javier; Merrill, Joan T; Niewold, Timothy B; Park, So-Yeon; Petri, Michelle A; Pons-Estel, Bernardo A; Ramsey-Goldman, Rosalind; Reveille, John D; Song, Yeong Wook; Stevens, Anne M; Tsao, Betty P; Vila, Luis M; Vyse, Timothy J; Yu, Chack-Yung; Guthridge, Joel M; Bruner, Gail R; Langefeld, Carl D; Montgomery, Courtney; Harley, John B; Scofield, R Hal; Gaffney, Patrick M; Moser, Kathy L

2011-01-07

Systemic lupus erythematosus (SLE) is considered to be the prototypic autoimmune disease, with a complex genetic architecture influenced by environmental factors. We sought to replicate a putative association at 11p13 not yet exceeding genome-wide significance (p < 5 × 10(-8)) identified in a genome-wide association study (GWAS). Our GWA scan identified two intergenic SNPs located between PDHX and CD44 showing suggestive evidence of association with SLE in cases of European descent (rs2732552, p = 0.004, odds ratio [OR] = 0.78; rs387619, p = 0.003, OR = 0.78). The replication cohort consisted of >15,000 subjects, including 3562 SLE cases and 3491 controls of European ancestry, 1527 cases and 1811 controls of African American (AA) descent, and 1265 cases and 1260 controls of Asian origin. We observed robust association at both rs2732552 (p = 9.03 × 10(-8), OR = 0.83) and rs387619 (p = 7.7 × 10(-7), OR = 0.83) in the European samples with p(meta) = 1.82 × 10(-9) for rs2732552. The AA and Asian SLE cases also demonstrated association at rs2732552 (p = 5 × 10(-3), OR = 0.81 and p = 4.3 × 10(-4), OR = 0.80, respectively). A meta-analysis of rs2732552 for all racial and ethnic groups studied produced p(meta) = 2.36 × 10(-13). This locus contains multiple regulatory sites that could potentially affect expression and functions of CD44, a cell-surface glycoprotein influencing immunologic, inflammatory, and oncologic phenotypes, or PDHX, a subunit of the pyruvate dehydrogenase complex.

Yes, Lupus Does Occur in Men

MedlinePlus

... out to other men who, like you, are learning to live and cope with lupus. You can connect with other men with lupus through the Lupus Foundation of America network of chapters and support groups . Related Resources Men ...

Early Lupus Project - A multicentre Italian study on systemic lupus erythematosus of recent onset.

PubMed

Sebastiani, G D; Prevete, I; Piga, M; Iuliano, A; Bettio, S; Bortoluzzi, A; Coladonato, L; Tani, C; Spinelli, F R; Fineschi, I; Mathieu, A

2015-10-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with a high degree of variability at onset that is problematic for a correct and prompt diagnosis. We undertook this project with the purpose of collecting an inception cohort of Italian patients with recent-onset SLE, in order to obtain information on the main clinical and serological characteristics at the beginning of the disease. In this first report we describe the characteristics of this cohort at study entry. All patients with a diagnosis of SLE (1997 ACR criteria) and a disease duration less than 12 months were consecutively enrolled between 1 January 2012 and 31 December 2013 in a multicentre prospective study. Information on clinical and serological characteristics at study entry and then every six months was collected into a specific electronic database. Statistical analysis was performed by means of the Openstat program. Among 122 patients enrolled (103 F) 94.3% were Caucasians. Mean age (SD) of patients at study entry was 37.3 (14.3) years, mean age at disease onset was 34.8 (14.3) years, mean age at diagnosis was 36.9 (14.3) years, and mean disease duration was 2.9 (3.9) months. The frequency of the manifestations included in the 1997 ACR criteria was as follows: ANA 97.5%, immunologic disorders (anti-dsDNA, anti-Sm, antiphospholipid antibodies) 85.2%, arthritis 61.8%, haematologic disorders 55.7%, malar rash 31.1%, photosensitivity 29.5%, serositis 27%, renal disorders 27%, oral/nasal ulcers 11.5%, neurologic disorders 8.2%, and discoid rash 5.7%. The cumulative frequency of mucocutaneous symptoms was 77.8%. At enrolment, autoantibody frequency was: ANA 100%, anti-dsDNA 83.6%, anti-SSA 28%, anticardiolipin 24.5%, anti-nRNP 20.4%, anti-beta2GPI 17.2%, lupus anticoagulant 16.3%, anti-Sm 16%, and anti-SSB 13.1%. In this paper we describe the main clinical and serological characteristics of an Italian inception cohort of patients with recent-onset SLE. At disease onset, mucocutaneous

Mood Disorders in Systemic Lupus Erythematosus

PubMed Central

Hanly, John G.; Su, Li; Urowitz, Murray B.; Romero-Diaz, Juanita; Gordon, Caroline; Bae, Sang-Cheol; Bernatsky, Sasha; Clarke, Ann E.; Wallace, Daniel J.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Ginzler, Ellen M.; Petri, Michelle; Bruce, Ian N.; Dooley, M. A.; Fortin, Paul; Gladman, Dafna D.; Sanchez-Guerrero, Jorge; Steinsson, Kristjan; Ramsey-Goldman, Rosalind; Khamashta, Munther A.; Aranow, Cynthia; Alarcón, Graciela S.; Fessler, Barri J.; Manzi, Susan; Nived, Ola; Sturfelt, Gunnar K.; Zoma, Asad A.; van Vollenhoven, Ronald F.; Ramos-Casals, Manuel; Ruiz-Irastorza, Guillermo; Lim, S. Sam; Kalunian, Kenneth C.; Inanc, Murat; Kamen, Diane L.; Peschken, Christine A.; Jacobsen, Soren; Askanase, Anca; Theriault, Chris; Thompson, Kara; Farewell, Vernon

2015-01-01

Objective To determine the frequency, clinical and autoantibody associations and outcome of mood disorders in a multi-ethnic/racial, prospective, inception cohort of SLE patients. Methods Patients were assessed annually for mood disorders (4 types as per DSM-IV) and 18 other neuropsychiatric (NP) events. Global disease activity (SLEDAI-2K), SLICC/ACR damage index (SDI) and SF-36 subscale, mental (MCS) and physical (PCS) component summary scores were collected. Time to event, linear and ordinal regressions and multi-state models were used as appropriate. Results Of 1,827 SLE patients, 88.9% were female, 48.9% Caucasian, mean ± SD age 35.1±13.3 years, disease duration 5.6±4.8 months and follow-up 4.73±3.45 years. Over the study 863 (47.2%) patients had 1,627 NP events. Mood disorders occurred in 232/1827 (12.7%) patients and 98/256 (38.3%) events were attributed to SLE. The estimated cumulative incidence of any mood disorder after 10 years was 17.7% (95%CI=[15.1%,20.2%]). There was a greater risk of mood disorder in patients with concurrent NP events (p ≤ 0.01) and lower risk with Asian race/ethnicity (p=0.01) and immunosuppressive drugs (p=0.003). Mood disorders were associated with lower mental health subscale and MCS scores but not with SLEDAI-2K, SDI scores or lupus autoantibodies. Antidepressants were used in 168/232 (72.4%) patients with depression. 126/256 (49.2%) mood disorders resolved in 117/232 (50.4%) patients. Conclusion Mood disorders, the second most frequent NP event in SLE patients, have a negative impact on HRQoL and improve over time. The lack of association with global SLE disease activity, cumulative organ damage and lupus autoantibodies emphasize their multifactorial etiology and a role for non-lupus specific therapies. PMID:25778456

Causes and predictors of mortality in hospitalized lupus patient in Sarawak General Hospital, Malaysia.

PubMed

Teh, C L; Ling, G R

2013-01-01

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that can be life threatening and fatal if left untreated. Causes and prognostic indicators of death in SLE have been well studied in developed countries but lacking in developing countries. We aimed to investigate the causes of mortality in hospitalized patients with SLE and determine the prognostic indicators of mortality during hospitalization in our center. All SLE patients who were admitted to Sarawak General Hospital from January 1, 2006 to December 31, 2010, were followed up in a prospective study using a standard protocol. Demographic data, clinical features, disease activities and damage indices were collected. Logistic regression and Cox regression analysis were used to determine the prognostic indicators of mortality in our patients. There were a total of 251 patients in our study, with the female to male ratio 10 to 1. Our study patients were of multiethnic origins. They had a mean age of 30.5 ± 12.2 years and a mean duration of illness of 36.5 ± 51.6 months. The main involvements were hematologic (73.3%), renal (70.9%) and mucocutaneous (67.3%). There were 26 deaths (10.4%), with the main causes being: infection and flare (50%), infection alone (19%), flare alone (19%) and others (12%). Independent predictors of mortality in our cohort of SLE patients were the presence of both infection and flare of disease (hazard ratio (HR) 5.56) and high damage indices at the time of admission (HR 1.91). Infection and flare were the main causes of death in hospitalized Asian patients with SLE. The presence of infection with flare and high damage indices at the time of admission were independent prognostic indicators of mortality.

Exploring Differences in the Aspirin-Colorectal Cancer Association by Sex and Race/Ethnicity: The Multiethnic Cohort Study.

PubMed

Park, Song-Yi; Wilkens, Lynne R; Kolonel, Laurence N; Monroe, Kristine R; Haiman, Christopher A; Marchand, Loïc Le

2017-02-01

Evidence has accumulated that long-term use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) protects against colorectal cancer. We tested whether the inverse associations between NSAIDs and colorectal cancer is similarly observed across sexes and five racial/ethnic groups (Japanese, Latino, African American, Native Hawaiian, and white) in the Multiethnic Cohort (MEC) Study. During a mean follow-up of 16.1 years, we identified 4,882 invasive incident colorectal cancer cases among 183,199 eligible participants. Cox proportional hazards models were used to calculate HRs and 95% confidence intervals (CI). Use of aspirin and other NSAIDs was associated with a lower incidence of colorectal cancer in men (HR = 0.77; 95% CI, 0.69-0.86 for current vs. never users of aspirin) but not in women (P interaction = 0.005). Among male current users, a reduced risk was observed with ≥6 years of aspirin or total NSAID use. The inverse association with current NSAID use in men was observed in all racial/ethnic groups, except for Native Hawaiians, and was stronger in whites. Our findings suggest that the benefit of NSAIDs for colorectal cancer may be strongest for white men and generalizes to African American, Japanese, and Latino, but not to Native Hawaiian men. The lack of inverse association observed in women and Native Hawaiian men in the MEC should be interpreted with caution. As only very few ethnic/racial groups are likely to be represented in trials of NSAIDs and colorectal cancer, it is important to conduct prospective observational studies in various populations to test the generalizability of their results. Cancer Epidemiol Biomarkers Prev; 26(2); 162-9. ©2016 AACR. ©2016 American Association for Cancer Research.

Disparity in liver cancer incidence and chronic liver disease mortality by nativity in Hispanics: The Multiethnic Cohort.

PubMed

Setiawan, Veronica Wendy; Wei, Pengxiao C; Hernandez, Brenda Y; Lu, Shelly C; Monroe, Kristine R; Le Marchand, Loic; Yuan, Jian Min

2016-05-01

Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are major causes of morbidity and mortality among Hispanics. Disparities in the incidence of HCC and in CLD deaths by nativity in Hispanics have been reported. Whether individual-level risk factors could explain these disparities was assessed in a prospective study of 36,864 Hispanics (18,485 US-born and 18,379 foreign-born) in the Multiethnic Cohort. Risk factors were assessed with a baseline questionnaire and Medicare claim files. During a 19.6-year follow-up, 189 incident cases of HCC and 298 CLD deaths were identified. The HCC incidence rate was almost twice as high for US-born Hispanic men versus foreign-born Hispanic men (44.7 vs 23.1), but the rates were comparable for women (14.5 vs 13.4). The CLD mortality rate was about twice as high for US-born Hispanics versus foreign-born Hispanics (66.3 vs 35.1 for men and 42.2 vs 19.7 for women). Heavy alcohol consumption was associated with HCC and CLD in foreign-born individuals, whereas the current smoking status, hepatitis B/C viral infection, and diabetes were associated with both HCC and CLD. After adjustments for these risk factors, the hazard rate ratios for HCC and CLD death were 1.58 (95% confidence interval, 1.00-2.51) and 1.85 (95% confidence interval, 1.25-2.73), respectively, for US-born Hispanics versus foreign-born Hispanics. US-born Hispanics, particularly males, are at greater risk for HCC and death from CLD than foreign-born Hispanics. Overall known differences in risk factors do not account for these disparities. Future studies are warranted to identify factors that contribute to the elevated risk of HCC development and CLD death in US-born Hispanics. Cancer 2016;122:1444-1452. © 2016 American Cancer Society. © 2016 American Cancer Society.

Association between various sedentary behaviours and all-cause, cardiovascular disease and cancer mortality: the Multiethnic Cohort Study

PubMed Central

Kim, Yeonju; Wilkens, Lynne R; Park, Song-Yi; Goodman, Marc T; Monroe, Kristine R; Kolonel, Laurence N

2013-01-01

Background It has been proposed that time spent sitting increases all-cause mortality, but evidence to support this hypothesis, especially the relative effects of various sitting activities alone or in combination, is very limited. Methods The association between various sedentary behaviours (time spent: sitting watching television (TV); in other leisure activities; in a car/bus; at work; and at meals) and mortality (all-cause and cause-specific) was examined in the Multiethnic Cohort Study, which included 61 395 men and 73 201 women aged 45–75 years among five racial/ethnic groups (African American, Latino, Japanese American, Native Hawaiian and White) from Hawaii and Los Angeles, USA. Results Median follow-up was 13.7 years and 19 143 deaths were recorded. Total daily sitting was not associated with mortality in men, whereas in women the longest sitting duration (≥10 h/day vs <5 h/day) was associated with increased all-cause (11%) and cardiovascular (19%) mortality. Multivariate hazard ratios (HR) for ≥5 h/day vs <1 h/day of sitting watching TV were 1.19 in men (95% confidence interval (CI) 1.10–1.29) and 1.32 in women (95% CI 1.21–1.44) for all-cause mortality. This association was consistent across four racial/ethnic groups, but was not seen in Japanese Americans. Sitting watching TV was associated with an increased risk for cardiovascular mortality, but not for cancer mortality. Time spent sitting in a car/bus and at work was not related to mortality. Conclusions Leisure time spent sitting, particularly watching television, may increase overall and cardiovascular mortality. Sitting at work or during transportation was not related to mortality. PMID:24062293

Ethnographic Depiction of a Multiethnic School: A Comparison to Desegregated Settings.

ERIC Educational Resources Information Center

Semons, Maryann

This report compares the findings of a recent ethnographic study of a multiethnic urban high school to some of the highlights of a series of ten-year-old ethnographic studies on court-ordered desegregated school settings. The study of the multiethnic urban school employed an ethnographic design whereby a participant-observer interviewed students…

Monogenic Lupus.

PubMed

Lo, Mindy S

2016-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease known for its clinical heterogeneity. Over time, new insights into the complex genetic origin of SLE have started to explain some of this clinical variability. These findings, reviewed here, have also yielded important understanding in the immune mechanisms behind SLE pathogenesis. Several new monogenic disorders with lupus-like phenotype have been described. These can be organized into physiologic pathways that parallel mechanisms of disease in SLE. Examples include genes important for DNA damage repair (e.g., TREX1), nucleic acid sensing and type I interferon overproduction (e.g., STING, TREX1), apoptosis (FASLG), tolerance (PRKCD), and clearance of self-antigen (DNASE1L3). Further study of monogenic lupus may lead to better genotype/phenotype correlations in SLE. Eventually, the ability to understand individual patients according to their genetic profile may allow the development of more targeted and personalized approaches to therapy.

[Lupus nephropathy in black patients with systemic lupus erythematosus in Senegal: 43 cases].

PubMed

Ka, E F; Cisse, M M; Lemrabott, A T; Fall, S; Diallo, M; Diallo, S; Faye, M; Niang, A; Diouf, B

2013-01-01

This study sought to assess the prevalence of lupus nephropathy and to determine its clinical, histological, therapeutic and outcome profiles. This retrospective study examined records covering a 10-year period from 1999 to 2009 at the nephrology department of the Aristide Le Dantec University Hospital Center. The records showed 43 patients with systemic lupus erythematosus (SLE), and 72% had lupus nephritis. The patients' mean age was 32.9 years; 40 were women and 3 men, for a sex ratio of 0.075. The lupus nephritis led to discovery of SLE in 27.9%. The mean proteinuria concentration was 2.01 g/dL. Seventeen patients had impaired renal function, and 26 had renal biopsies. It found class II nephritis in 2 patients, class IV in 10, and class V in 12. In addition, fifteen patients received combined corticosteroid + immunosuppressant treatment. Four patients died during the study period, one from SLE activity, two from complications of renal failure, and the fourth from sepsis. A larger study would be useful to assess more acurately the prevalence of various classes and severity of lupus nephropathy among blacks living in sub-Saharan Africa.

Inverse Association of Parkinson Disease With Systemic Lupus Erythematosus: A Nationwide Population-based Study.

PubMed

Liu, Feng-Cheng; Huang, Wen-Yen; Lin, Te-Yu; Shen, Chih-Hao; Chou, Yu-Ching; Lin, Cheng-Li; Lin, Kuen-Tze; Kao, Chia-Hung

2015-11-01

The effects of the inflammatory mediators involved in systemic lupus erythematous (SLE) on subsequent Parkinson disease have been reported, but no relevant studies have focused on the association between the 2 diseases. This nationwide population-based study evaluated the risk of Parkinson disease in patients with SLE.We identified 12,817 patients in the Taiwan National Health Insurance database diagnosed with SLE between 2000 and 2010 and compared the incidence rate of Parkinson disease among these patients with that among 51,268 randomly selected age and sex-matched non-SLE patients. A Cox multivariable proportional-hazards model was used to evaluate the risk factors of Parkinson disease in the SLE cohort.We observed an inverse association between a diagnosis of SLE and the risk of subsequent Parkinson disease, with the crude hazard ratio (HR) being 0.60 (95% confidence interval 0.45-0.79) and adjusted HR being 0.68 (95% confidence interval 0.51-0.90). The cumulative incidence of Parkinson disease was 0.83% lower in the SLE cohort than in the non-SLE cohort. The adjusted HR of Parkinson disease decreased as the follow-up duration increased and was decreased among older lupus patients with comorbidity.We determined that patients with SLE had a decreased risk of subsequent Parkinson disease. Further research is required to elucidate the underlying mechanism.

Inverse associations of dietary fiber and menopausal hormone therapy with colorectal cancer risk in the Multiethnic Cohort Study.

PubMed

Park, Song-Yi; Wilkens, Lynne R; Kolonel, Laurence N; Henderson, Brian E; Le Marchand, Loïc

2016-09-15

In the Multiethnic Cohort Study, we previously reported that dietary fiber intake was inversely associated with colorectal cancer risk in men only. In women, the inverse relationship was weaker and appeared to be confounded by menopausal hormone therapy (MHT). We re-examined this observation with a greatly increased power. Using Cox proportional hazards models, we analyzed data from 187,674 participants with 4,692 cases identified during a mean follow-up period of 16 years. In multivariable-adjusted models, dietary fiber intake was inversely associated with colorectal cancer risk in both sexes: HR = 0.73, 95% CI: 0.61-0.89 for highest vs. lowest quintile, ptrend  = 0.0020 in men and HR = 0.76, 95% CI: 0.62-0.91, ptrend  = 0.0067 in women. Postmenopausal women who ever used MHT had a 19% lower risk of colorectal cancer (95% CI: 0.74-0.89) compared with MHT never users. In a joint analysis of dietary fiber and MHT, dietary fiber intake was associated with a lower colorectal cancer risk in MHT never users (HR = 0.75, 95% CI: 0.59-0.95, ptrend  = 0.045), but did not appear to further decrease the colorectal cancer risk of MHT ever users (ptrend  = 0.11). Our results support the overall protective roles of dietary fiber and MHT against colorectal cancer and suggest that dietary fiber may not lower risk further among women who ever used MHT. If confirmed, these results would suggest that MHT and dietary fiber may share overlapping mechanisms in protecting against colorectal cancer. © 2016 UICC.

Visit-to-visit SBP variability and cardiovascular disease in a multiethnic primary care setting: 10-year retrospective cohort study.

PubMed

Chia, Yook Chin; Ching, Siew Mooi; Lim, Hooi Min

2017-05-01

The current study aims to determine the relationship of long-term visit-to-visit variability of SBP to cardiovascular disease (CVD) in a multiethnic primary care setting. This is a retrospective study of a cohort of 807 hypertensive patients over a period of 10 years. Three-monthly clinic blood pressure readings were used to derive blood pressure variability (BPV), and CVD events were captured from patient records. Mean age at baseline was 57.2 ± 9.8 years with 63.3% being women. The BPV and mean SBP over 10 years were 14.7 ± 3.5 and 142 ± 8 mmHg, respectively. Prevalence of cardiovascular event was 13%. In multivariate logistic regression analysis, BPV was the predictor of CVD events, whereas the mean SBP was not independently associated with cardiovascular events in this population. Those with lower SBP and lower BPV had fewer cardiovascular events than those with the same low mean SBP but higher BPV (10.5 versus 12.8%). Similarly those with higher mean SBP but lower BPV also had fewer cardiovascular events than those with the same high mean and higher BPV (11.6 versus 16.7%). Other variables like being men, diabetes and Indian compared with Chinese are more likely to be associated with cardiovascular events. BPV is associated with an increase in CVD events even in those who have achieved lower mean SBP. Thus, we should prioritize not only control of SBP levels but also BPV to reduce CVD events further.

Dietary patterns using the Food Guide Pyramid groups are associated with sociodemographic and lifestyle factors: the multiethnic cohort study.

PubMed

Park, Song-Yi; Murphy, Suzanne P; Wilkens, Lynne R; Yamamoto, Jennifer F; Sharma, Sangita; Hankin, Jean H; Henderson, Brian E; Kolonel, Laurence N

2005-04-01

Dietary patterns have been used to identify typical combinations of foods that may be associated with disease risks. We defined dietary patterns among 195,298 participants of the Multiethnic Cohort Study in Hawaii and Los Angeles in 1993-1996. Intakes of Food Guide Pyramid groups were calculated from a quantitative FFQ for subjects of 5 ethnic groups (African Americans, Hawaiians, Japanese Americans, Latinos, and whites). Three distinct dietary patterns, "Fat and Meat," "Vegetables," and "Fruit and Milk," were identified by exploratory factor analysis with a varimax rotation and validated by confirmatory factor analysis. Similar factor loadings were found for each of 10 ethnic-gender groups in stratified analyses. The odds ratios (OR) for being above the median scores for each factor were calculated. Age, gender, and ethnicity had relatively strong associations with dietary patterns whereas education showed only weak associations. BMI > or = 30 was strongly positively associated with the Fat and Meat pattern (OR = 2.14, 95% CI: 2.08-2.20, vs. BMI < 25). Current smokers showed a positive association with the Fat and Meat pattern (OR = 1.67, CI: 1.62-1.72, vs. nonsmokers) and inverse associations with the Vegetables (OR = 0.66, CI: 0.64-0.68) and Fruit and Milk patterns (OR = 0.53, CI: 0.52-0.55). Physical activity was positively associated with the Vegetables and Fruit and Milk patterns but not with the Fat and Meat pattern. These findings support the hypothesis that dietary patterns are influenced by interrelated sociocultural, demographic, and other lifestyle factors and may be useful in investigations of diet-disease relations.

Chinese lupus treatment and research group (CSTAR) registry: X. family history in relation to lupus clinical and immunological manifestations.

PubMed

Leng, Xiaomei; Li, Mengtao; Li, Xiangpei; Zhang, Xiao; Liu, Shengyun; Wu, Lijun; Ma, Li; Bi, Liqi; Zuo, Xiaoxia; Sun, Lingyun; Huang, Cibo; Zhao, Jiuliang; Zhao, Yan; Zeng, Xiaofeng

2018-01-01

This study aimed to examine the associations between family history and clinical manifestations and immunologic characteristics of lupus in China. Based on their family history, lupus patients from the Chinese lupus treatment and research group (CSTAR) registry were categorised: familial lupus (FL), family history of other rheumatic disorders (RD), and sporadic lupus (SL). Demographic data, clinical manifestations, and laboratory data were compared among these three groups. A total of 2,104 patients from CSTAR were included, with 34 (1.6%) in the FL group, 50 (2.4%) in the RD group, and 2,020 (96.0%) in the SL group. There were no significant differences in age or gender among these groups (p=0.36 and p=0.75, respectively). The prevalence of discoid rash and positivity of anti-RNP antibodies differed significantly among the three groups. Photosensitivity and neurological disorder were marginally significantly different among the three groups (p=0.05). No statistical differences were observed in other clinical manifestations or laboratory results. In the FL group, first-degree relatives (25/34, 73.5%) had higher susceptibility to lupus. Rheumatoid arthritis (RA) (35/50, 70.0%) was the most frequent non-lupus rheumatic disorder in the RD group. Among lupus patients, the rate of familial lupus was lower in Chinese patients than among other ethnicities. Familial lupus cases are found mainly among their first-degree relatives. A family history of lupus did not significantly affect clinical phenotypes, except for higher frequency of discoid rash and anti-RNP in the FL group, and more anti-RNP positivity in the RD group.

[Pulmonary manifestations in systemic lupus erythematosus].

PubMed

Vincze, Krisztina; Odler, Balázs; Müller, Veronika

2016-07-01

Systemic lupus erythematosus is the most common connective tissue disease that is associated with pulmonary manifestations. Although lupus has the potential to affect any organ, lung involvement is observed during the course of the disease in most cases and it is prognostic for outcome. Pulmonary manifestations in lupus can be classified into five groups based on the anatomical involvement: pleura, lung parenchyma, bronchi and bronchioli, lung vasculature and respiratory muscles can be involved. The most common respiratory manifestations attributable to lupus are pleuritis with or without pleural effusion, pulmonary vascular disease, upper and lower airway dysfunction, parenchymal disease, and diaphragmatic dysfunction (shrinking lung syndrome). In this article the authors summarize lung involvement of lupus, its diagnosis, therapy and prognosis. Orv. Hetil., 2016, 157(29), 1154-1160.

Clinical and immunological pattern and outcome of Egyptian systemic lupus erythematosus patients: a single center experience.

PubMed

Mahmoud, G A; Shahin, A A; Zayed, H S; Moghazy, A; Eissa, B M

2018-01-01

Objective The objective of this study was to describe the clinical and immunological pattern and disease outcome in Egyptian systemic lupus erythematosus patients. Patients and methods The medical records of 770 systemic lupus erythematosus patients who were followed from 2002-2015 at Kasr Alainy Hospital, Cairo University, were retrospectively reviewed. Results There were 707 (91.8%) females. The mean age at disease onset was 22.1 ± 8.6 and the disease duration was 6.1 ± 4.5 years. The main clinical manifestations were mucocutaneous (90.8% with oral ulcers affecting 52.5%), arthritis (80.3%), nephritis (67.8%), hematologic involvement (64.9%), serositis (55.2%) and neuropsychiatric manifestations (44.3%). The frequencies of antinuclear antibodies were 94.3%, anti-dsDNA 74.8%, anti-Smith 11%, anticardiolipin antibodies 29.5% and lupus anticoagulant 19.8%. Infections, predominantly bacterial, affected 337 (43.8%) patients. Thirty-three (4.3%) patients died. The main causes of death were sepsis and disease activity. The five- and 10-year survival rates for the total cohort were 97.4% and 96.3%, respectively, and were 96% and 92%, respectively for those with nephritis ( p = 0.008). Autoimmune hemolytic anemia, thrombocytopenia, elevated serum creatinine, a higher damage index, infections, a higher glucocorticoid dose and cyclophosphamide use ≥ six months were associated with an increased risk of mortality with odds ratios of 3.69, p < 0.01; 4.12, p < 0.001; 1.54, p < 0.001; 1.43, p < 0.001; 5.08, p < 0.001; 5.04, p < 0.001 and 2.25, p = 0.03, respectively. Conclusion Compared to other cohorts, a relatively lower mean age at systemic lupus erythematosus onset and higher frequencies of oral ulcers, serositis and nephritis were found.

Childhood-onset bullous systemic lupus erythematosus.

PubMed

Lourenço, D M R; Gomes, R Cunha; Aikawa, N E; Campos, L M A; Romiti, R; Silva, C A

2014-11-01

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Parental history of lupus and rheumatoid arthritis and risk in offspring in a nationwide cohort study: does sex matter?

PubMed

Somers, Emily C; Antonsen, Sussie; Pedersen, Lars; Sørensen, Henrik Toft

2013-04-01

To examine the familial risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), including juvenile rheumatoid/idiopathic arthritis (JRA), in a population-based setting; and to determine whether patterns of transmission differ according to the sex of the parent or offspring, in order to provide insight into the potential impact of X-chromosomal factors on sex disparities in these autoimmune diseases. A population-based cohort of parent-offspring triads from Denmark (1977-2010) was established. SLE and RA incidence rates among offspring were calculated, and Cox regression was performed to assess the sex-specific risk of disease in offspring according to maternal or paternal disease history. Among 3 513 817 parent-offspring triads, there were 1258 SLE cases among offspring (1095 female, 163 male) and 9118 cases of RA/JRA (6086 female, 3032 male). Among female offspring, SLE risk was nearly the same according to maternal (HR 14.1) or paternal (HR 14.5) history (p=NS); likewise among male offspring, risk according to maternal (HR 5.5) and paternal (no cases) history were similar (p=NS). For RA, all risk estimates were similar, regardless of the sex of the offspring or parent (HR 2.6-2.9; p=NS). The authors quantified the familial risk of SLE and RA in a nationwide cohort study. For both diseases, transmission was comparable among both female and male offspring of maternal and paternal cases. These data provide evidence at the population level that X-chromosomal factors do not play a major role in sex disparities associated with the risk of SLE and RA.

Systemic lupus erythematosus in three ethnic groups. V. Acculturation, health-related attitudes and behaviors, and disease activity in Hispanic patients from the LUMINA cohort. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.

PubMed

Alarcón, G S; Rodríguez, J L; Benavides, G; Brooks, K; Kurusz, H; Reveille, J D

1999-08-01

To assess the relationship between acculturation and clinical, socioeconomic-demographic, and behavioral/psychosocial features in Hispanic patients with systemic lupus erythematosus (SLE) from the LUMINA (Lupus in Minority Populations, Nature versus Nurture) cohort. An empirically derived questionnaire was administered to 67 Mexican American SLE patients participating in a longitudinal study of outcome. This questionnaire inquired about place of birth, upbringing and length of stay in the United States, language (proficiency, usage, and preferences; English/bilingual versus Spanish), type of neighborhood, self-identity, and social interactions. Responses to this questionnaire and an informal interaction with a single bilingual, bicultural Mexican American research assistant were used to generate a score on a 10-cm anchored visual analog scale (VAS) (0 = no acculturation and 10 = maximum acculturation). The responses to the questionnaire were then quantified and scored by a physician who was unaware of the VAS. A composite score was then obtained utilizing 4 of the 6 components of the instrument. The VAS was found to have adequate sensitivity (91%), specificity (88%), and overall predictive value (89%) when the composite score was used as the validity criterion. Therefore, the VAS was used in all subsequent analyses; the median in this VAS separated patients into high and low acculturation groups. The relationship between acculturation and sociodemographic, behavioral/psychosocial (social support, abnormal illness-related behaviors, and helplessness) and clinical variables (disease duration, onset type, number of American College of Rheumatology criteria met, disease activity, and damage) at study entry was then explored. Patients in the low acculturation group had fewer years of education, were less likely to have private health insurance, and had less social support as compared with those in the high acculturation group; they also exhibited less disease activity

Childhood-onset systemic lupus erythematosus in Singapore: clinical phenotypes, disease activity, damage, and autoantibody profiles.

PubMed

Tan, J H T; Hoh, S F; Win, M T M; Chan, Y H; Das, L; Arkachaisri, T

2015-08-01

Childhood-onset systemic lupus erythematosus (cSLE) is a multisystem autoimmune disease characterized by immune dysregulation affecting patients less than 18 years old. One-fifth of SLE cases are diagnosed during childhood. cSLE presents differently from adults and has a more severe and aggressive course. We describe the clinical and antibody profiles in our cSLE Singapore cohort. All cSLE patients who satisfied the 1997 American College of Rheumatology diagnostic criteria were captured in our lupus registry from January 2009 to January 2014. Data including demographic, cumulative clinical, serologic data, and damage indices were collected. Adjusted mean SLEDAI-2K (AMS) was used to summarize disease activity over multiple visits. Cluster analysis using non-hierarchical K-means procedure was performed on eight selected antibodies. The 64 patients (female:male ratio 5:1; Chinese 45.3%, Malay 28.1%, Indian 9.4%, and other races 17.2%) had a mean onset age of 11.5 years (range 2.1-16.7) and mean age at diagnosis was 11.9 years (range 2.6-18.0). Our study demonstrated differences in clinical manifestations for which hematologic involvement was the most common manifestation with less renal disease and uncommon neurologic manifestation as compared to other cSLE cohorts reported in our region. Antibody clusters were identified in our cohort but their clinical association/discrimination and outcome prediction required further validation study. Outcomes of our cohort in regard to disease activity after therapy and organ damages were comparable if not better to other cSLE cohorts elsewhere. Steroid-related damage, including symptomatic multifocal avascular necrosis and cataract, were not uncommon locally. Infection remains the major cause of death for the continent. Nevertheless, the five year survival rate of our cohort (98.4%) was high. © The Author(s) 2015.

Accrual of organ damage over time in patients with systemic lupus erythematosus.

PubMed

Gladman, Dafna D; Urowitz, Murray B; Rahman, Proton; Ibañez, Dominique; Tam, Lai-Shan

2003-09-01

To determine the pattern of accumulation of damage in an inception cohort of patients with systemic lupus erythematosus (SLE) followed yearly for at least 15 years, and to identify damage items that might be related to corticosteroid therapy. An inception cohort was identified from among patients with SLE followed prospectively in the University of Toronto Lupus Clinic. Only patients who had at least yearly evaluations and were followed for at least 15 years were included. Using the SLICC/ACR damage index (SDI) accumulated damage was calculated at yearly intervals. Each new organ system involved was designated as either definitely, possibly, or not at all related to corticosteroid therapy. Of the 73 patients, 85% were women and 87.7% were Caucasian. Their mean age at diagnosis was 34.9 years. The mean (range) SLEDAI at presentation was 11.9 (0-37). Prednisone was used by 87.7% of the patients (mean maximum dose 37.7 mg/day, mean cumulative dose 36.8 g) for a mean of 117.1 months. Antimalarial drugs were used by 70% of the patients and 50% were taking immunosuppressive agents. The mean SDI for the whole cohort increased over time from 0.33 (0.89) during the first year to 1.90 (1.99) at 15 years. A significant proportion of the damage both early and late could be attributed to corticosteroid therapy, and this damage accumulated over time such that it constituted most of the damage at 15 years. While the overall accrual of damage is gradual, the specific systems demonstrate varying patterns of damage accrual.

Lupus and Kidney Disease (Lupus Nephritis)

MedlinePlus

... such as infections, viruses, toxic chemicals or pollutants (car fumes, factory smoke) may play a role in causing the disease. Men and women of all ages and races get lupus. However, about 90 percent of people ...

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c.

PubMed

Rudland, Victoria L; Hinchcliffe, Marcus; Pinner, Jason; Cole, Stuart; Mercorella, Belinda; Molyneaux, Lynda; Constantino, Maria; Yue, Dennis K; Ross, Glynis P; Wong, Jencia

2016-01-01

Glucokinase monogenic diabetes (GCK-maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5-1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Treatment of Cutaneous Lupus Erythematosus

PubMed Central

Kim, Grace K.; Del Rosso, James Q.

2013-01-01

The treatment of cutaneous lupus erythematosus is centered upon formulating a regimen of topical and systemic therapies designed to reduce disease activity and minimize cosmetic damage. Sun avoidance and sunscreen are important preventative measures proven to minimize cutaneous lupus erythematosus exacerbations. Limited disease is typically managed with topical corticosteroids or calcineurin inhibitors. Antimalarial therapy is the gold standard of systemic therapy. Many other treatments have been studied in patients with recalcitrant cutaneous lupus erythematosus, and their use must be evaluated based on individual risk-benefit concerns. R-salbutamol and pulsed dye laser therapy have proven to be effective topical alternatives. Additional systemic agents include retinoids, immunosuppressants, immunomodulators, biologics, and other experimental therapies with novel modes of action. According to the Oxford Centre for Evidence-based Medicine criteria for evaluating the strength of evidence supporting an individual treatment measure, no therapy for cutaneous lupus erythematosus has achieved Level 1 status. This demonstrates the need for randomized, controlled trials and systematic reviews of all cutaneous lupus erythematosus interventions in order to meet increasing standards and demand for evidence-based practice. PMID:23320123

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus.

PubMed

Pandhi, Deepika; Verma, Prashant; Singal, Archana; Sharma, Sonal; Tondon, Anupama

2012-01-01

Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon. We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.

European genetic ancestry is associated with a decreased risk of lupus nephritis.

PubMed

Richman, Ilana B; Taylor, Kimberly E; Chung, Sharon A; Trupin, Laura; Petri, Michelle; Yelin, Edward; Graham, Robert R; Lee, Annette; Behrens, Timothy W; Gregersen, Peter K; Seldin, Michael F; Criswell, Lindsey A

2012-10-01

African Americans, East Asians, and Hispanics with systemic lupus erythematosus (SLE) are more likely to develop renal disease than are SLE patients of European descent. This study was undertaken to investigate whether European genetic ancestry protects against the development of lupus nephritis, with the aim of exploring the genetic and socioeconomic factors that might explain this effect. This was a cross-sectional study of SLE patients from a multiethnic case collection. Participants were genotyped for 126 single-nucleotide polymorphisms (SNPs) informative for ancestry. A subset of participants was also genotyped for 80 SNPs in 14 candidate genes for renal disease in SLE. Logistic regression was used to test the association between European ancestry and renal disease. Analyses were adjusted for continental ancestries, socioeconomic status (SES), and candidate genes. Participants (n = 1,906) had, on average, 62.4% European, 15.8% African, 11.5% East Asian, 6.5% Amerindian, and 3.8% South Asian ancestry. Among the participants, 656 (34%) had renal disease. A 10% increase in the proportion of European ancestry estimated in each participant was associated with a 15% reduction in the odds of having renal disease, after adjustment for disease duration and sex (odds ratio 0.85, 95% confidence interval 0.82-0.87; P = 1.9 × 10(-30) ). Adjustment for other genetic ancestries, measures of SES, or SNPs in the genes most associated with renal disease (IRF5 [rs4728142], BLK [rs2736340], STAT4 [rs3024912], and HLA-DRB1*0301 and DRB1*1501) did not substantively alter this relationship. European ancestry is protective against the development of renal disease in SLE, an effect that is independent of other genetic ancestries, candidate risk alleles, and socioeconomic factors. Copyright © 2012 by the American College of Rheumatology.

Quality of Life in Cutaneous Lupus Erythematosus

PubMed Central

Klein, Rachel; Moghadam-Kia, Siamak; Taylor, Lynne; Coley, Christopher; Okawa, Joyce; LoMonico, Jonathan; Chren, Mary-Margaret; Werth, Victoria P.

2010-01-01

Background Little is known about quality of life in patients with cutaneous lupus erythematosus. Objective We sought to determine how cutaneous lupus affects quality of life and which independent variables are associated with poor quality of life. Methods 157 patients with cutaneous lupus completed surveys related to quality of life, including the Skindex-29 and the SF-36. Results Quality of life in cutaneous lupus is severely impaired, particularly with respect to emotional well-being. Patients with cutaneous lupus have worse quality of life than those with other common dermatologic conditions, such as acne, non-melanoma skin cancer, and alopecia. With respect to mental health status, patients with cutaneous lupus have similar or worse scores than patients with hypertension, type 2 diabetes mellitus, recent myocardial infarction, and congestive heart failure. Factors related to poor quality of life include female gender, generalized disease, severe disease, distribution of lesions, and younger age. Limitations The study was done at a single referral-only center. Conclusion Patients with cutaneous lupus have very impaired quality of life, particularly from an emotional perspective. PMID:21397983

The stellar population of the Lupus clouds

NASA Technical Reports Server (NTRS)

Hughes, Joanne; Hartigan, Patrick; Krautter, Joachim; Kelemen, Janos

1994-01-01

We present photometric and spectroscopic observations of the H alpha emission stars in the Lupus dark cloud complex. We estimate the effective temperatures of the stars from their spectral types and calculate the reddening towards each object from the (R-I) colors. From these data, we derive mass and age distributions for the Lupus stars using a new set of pre-main sequence evolutionar tracks. We compare the results for the Lupus stars with those for a similar population of young stellar objects in Taurus-Auriga and Chamaeleon and with the initial mass function for field stars in the solar neighborhood. From the H-R diagrams, Lupus appears to contain older stars than Taurus. The Lupus dark clouds form a greater proportion of low mass stars than the Taurus complex. Also, the proportion of low mass stars in Lupus is higher than that predicted by the Miller-Scalo initial mass function, and the lowest mass stars in Lupus are less active than similar T Tauri stars in other regions.

Murine Models of Systemic Lupus Erythematosus

PubMed Central

Perry, Daniel; Sang, Allison; Yin, Yiming; Zheng, Ying-Yi; Morel, Laurence

2011-01-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci from which several candidate genes have emerged. Meanwhile, induced models of lupus have provided insight into the role of environmental factors in lupus pathogenesis as well as provided a better understanding of cellular mechanisms involved in the onset and progression of disease. The SLE-like phenotypes present in these models have also served to screen numerous potential SLE therapies. Due to the complex nature of SLE, it is necessary to understand the effect specific targeted therapies have on immune homeostasis. Furthermore, knowledge gained from mouse models will provide novel therapy targets for the treatment of SLE. PMID:21403825

Urinary sediment suggests lupus nephritis histology.

PubMed

Martínez-Martínez, M U; Llamazares-Azuara, L M de G; Martínez-Galla, D; Mandeville, P B; Valadez-Castillo, F; Román-Acosta, S; Borjas-García, J A; Abud-Mendoza, C

2017-05-01

Objectives The objective of this paper was to evaluate correlations between kidney biopsy indexes (activity and chronicity) and urinary sediment findings; the secondary objective was to find which components of urinary sediment can discriminate proliferative from other classes of lupus nephritis. Methods Lupus nephritis patients scheduled for a kidney biopsy were included in our study. The morning before the kidney biopsy, we took urine samples from each patient. Receiver operating characteristic (ROC) curves were plotted to determine the area under the curve (AUC) of each test for detecting proliferative lupus nephritis; a classification tree was calculated to select a set of values that best-predicted lupus nephritis classes. Results We included 51 patients, 36 of whom were women (70.6%). Correlations of lupus nephritis activity index with the counts in the urinary sediment of erythrocytes (isomorphic and dysmorphic), acanthocytes, and leukocytes were 0.65 ( p < 0.0001) 0.62 ( p < 0.0001) and 0.22 ( p = 0.1228), respectively. Correlations of lupus nephritis chronicity index with the counts of erythrocytes, acanthocytes, and leukocytes were 0.60 ( p ≤ 0.0001), 0.52 ( p = 0.0001) and 0.17 ( p = 0.2300), respectively. Our classification tree had an accuracy of 84.3%. Conclusions Evaluation of urine sediment reflects lupus nephritis histology.

"Ich kam unter die Schweizer": Teaching Switzerland as a Multi-Ethnic Society

ERIC Educational Resources Information Center

Baumgartner, Karin

2012-01-01

This article describes a five-week module on "Switzerland as a multi-ethnic society" intended to counteract the popular image of Switzerland as a homogenous country concerned mostly with tourism, chocolate, and watches. Instead, the module treats Switzerland through topics such as the definition of identity in a multi-ethnic society, the…

Lupus pneumonitis as the initial presentation of systemic lupus erythematosus: case series from a single institution.

PubMed

Wan, S A; Teh, C L; Jobli, A T

2016-11-01

Objective The aim of this study was to examine the clinical features, treatment and outcome of systemic lupus erythematosus (SLE) patients in our centre who presented with lupus pneumonitis as the initial manifestation. Methods We performed a retrospective review of all patients who presented with lupus pneumonitis during the initial SLE manifestation from March 2006 to March 2015. Results There were a total of five patients in our study who presented with fever and cough as the main clinical features. All patients had pulmonary infiltrates on chest radiographs. High-resolution computed tomography, which was performed in two patients, showed ground glass opacities with patchy consolidations bilaterally. All patients received high-dose steroids, 80% received intravenous cyclophosphamide and 60% received intravenous immunoglobulin. Two patients died from severe lupus pneumonitis within 2 weeks of admission despite treatment with ventilation, steroids, cyclophosphamide and intravenous immunoglobulin. Conclusions Acute lupus pneumonitis is an uncommon presentation of SLE. Mortality in this case series is 40%.

Dietary intakes and health-related behaviours of Korean American women born in the USA and Korea: the Multiethnic Cohort Study.

PubMed

Park, Song-Yi; Murphy, Suzanne P; Sharma, Sangita; Kolonel, Laurence N

2005-10-01

This study assessed and compared heath-related behaviours and nutrient and food group intakes between US-born and Korea-born Korean American women. Cross-sectional analyses were performed for ethnic Koreans who participated in the Multiethnic Cohort Study in Hawaii and Los Angeles in 1993-1996. The sample included 492 Korean American women aged 45-75 years who were born in the USA (n = 274) or Korea (n = 218). Participants were recruited using driver's license files as a primary sampling source and completed a self-administered questionnaire, including a quantitative food frequency section. The proportion overweight or obese was 31.4% in US-born and 9.4% in Korea-born women. US-born women had higher intakes of total fat and fat as a percentage of energy, and lower intakes of sodium, vitamin C, beta-carotene and carbohydrate as a percentage of energy, than Korea-born women. Comparing intakes of food group servings from the Food Guide Pyramid, US-born women reported more whole grains, red meat and nuts, and less soy products, than did Korea-born women. US-born women also consumed fewer vegetables and fruit than those born in Korea. Few women in either group reported intakes that met the recommendations for dairy foods. Intake of discretionary fat from the Pyramid tip was higher in US-born than in Korea-born women. These findings indicate that the acculturation of Korean immigrants affects dietary intakes in ways that may alter risks of several chronic diseases. Further studies will be necessary to examine the effects of dietary acculturation on disease patterns.

A Prospective Study of Lupus and Rheumatoid Arthritis in Relation to Deployment in Support of Iraq and Afghanistan: The Millennium Cohort Study

DTIC Science & Technology

2011-01-01

personnel may experience several environmental and occupational expo- sures, including pesticides (environmental and topical), paints, solvents, and...uniform treatments) and environmental pesticides . 2.3. Outcomes. Lupus and RA were investigated using the baseline survey question “Has your doctor or...to newly report lupus were female , non- Hispanic black and Hispanic, not married, and of lower mental and physical health. The following variables

The incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus in New Zealand Maori and Pacific Island children: the Starship experience (2000-2010).

PubMed

Concannon, A; Rudge, S; Yan, J; Reed, P

2013-10-01

To describe the incidence, diagnostic clinical manifestations and severity of juvenile systemic lupus erythematosus (jSLE) in a cohort of New Zealand Maori and Pacific Island children compared to European children. A chart review was conducted of children with jSLE seen by the Starship paediatric rheumatology and/or renal services between January 2000 and November 2010. Diagnostic clinical data and lupus nephritis data at anytime were collated while classic British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were derived retrospectively. Thirty-two children were diagnosed with jSLE with an annual incidence of 0.52 per 100,000 per year. Compared with European children (0.31 per 100,000 per year) the incidence of jSLE was higher among Maori and Pacific (0.67 per 100,000 per year, p=0.06) and significantly higher among Asian children (1.17 per 100,000 per year, p=0.01). Compared with European children, Maori and Pacific children were more frequently diagnosed with lupus nephritis (80% vs 40%, p=0.09) and severe (WHO class 4 or 5) renal lesions (60% vs 40%, p=0.43) at presentation. Similarly, at any time during the study, lupus nephritis (100% vs 40%, p=0.001) and severe (WHO class 4 or 5) renal lesions (73.3% vs 40%, p=0.12) were more frequent among Maori and Pacific compared with European children. Furthermore, retrospective BILAG assessment of diagnostic disease severity demonstrated that Maori and Pacific children experienced the majority of severe "Category A" disease (56.8% vs 22.7%, p=0.17) which was predominantly renal (73.3% vs 40%, p=0.12) in nature. This is the first description of the incidence and clinical manifestations of jSLE in a cohort of New Zealand children. Although limited by the small numbers involved it confirmed anecdotal suspicions that the incidence of jSLE among Maori, Pacific and Asian children is higher than European children. Lupus nephritis is also more frequent and severe

The lupus impact tracker is responsive to changes in clinical activity measured by the systemic lupus erythematosus responder index.

PubMed

Devilliers, H; Bonithon-Kopp, C; Jolly, M

2017-04-01

Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.

Association of Asian ethnicity with disease activity in SLE: an observational study from the Monash Lupus Clinic.

PubMed

Golder, V; Connelly, K; Staples, M; Morand, E; Hoi, A

2013-11-01

Systemic lupus erythematosus (SLE), an autoimmune condition with diverse clinical manifestations, is reported to have different expression in populations of different ancestry. Most previous studies compared patients of different ethnic groups from geographically distinct cohorts. In our study, we aimed to characterize disease manifestations in patients of different ethnic groups from a single centre, and studied patterns of disease activity over time. Demographics, baseline disease characteristics and autoantibody profiles, and disease activity (SLEDAI) measured at each visit, were captured from all consenting patients prospectively followed between 2007 and 2011 in an urban teaching hospital lupus clinic. Ethnicity was self-reported. Asian ethnicity was significantly associated with more clinically severe SLE. Time-adjusted mean SLEDAI (p = 0.01) and maximum SLEDAI (p = 0.0018) were significantly higher in Asian patients. Asians were more likely to have renal disease (OR 2.9, 95% CI 1.4-5.98; p = 0.004) and persistently active disease (PAD) (OR 2.14, 95% CI 1.05-4.38, p = 0.04). Asian lupus patients also had a significantly higher proportion of autoantibody positivity to anti-dsDNA, anti-RNP, anti-Sm, anti-Ro and anti-La, as well as increased likelihood of hypocomplementaemia and immunosuppressant use. In this single-cohort study, Asian ethnicity was found to be associated with increased SLE disease activity. This suggests significant inter-ethnic genetic contributions to the regulation of autoimmune responses and disease severity in SLE.

Clinicopathological findings, treatment response and predictors of long-term outcome in a cohort of lupus nephritis patients managed according to the Euro-lupus regime: a retrospective analysis in Sri Lanka.

PubMed

Herath, Nalaka; Ratnatunga, Neelakanthi; Weerakoon, Kosala; Wazil, Abdul; Nanayakkara, Nishantha

2017-02-02

Despite the improvement in survival of patients with lupus nephritis (LN) globally, there is sparse data from Sri Lanka (SL). The current study aims to describe the clinicopathological findings, treatment response and predictors of long-term outcome of patients with WHO class III-IV LN in SL, managed according to the Euro-lupus regime. Of 72 patients, 64 were females. In half of them, LN was diagnosed within the 1st year of the illness. The most common presenting feature was sub-nephrotic proteinuria. Sixteen and twenty patients had nephrotic syndrome and abnormal renal function respectively at the time of diagnosis. Fifty-four patients (75%) responded to the Euro-lupus regimen [CR, 20 (28%); PR, 34(47%)]. Later at 6 months, 65 patients (90%) achieved remission [CR, 31(43%); PR, 34 (47%)]. Seven patients experienced treatment failure. During the total duration of follow up, 54 patients remained in complete or partial remission, 26 developed renal relapses, and 19 suffered severe infective episodes. Renal relapses were more common in people who achieved partial remission than complete remission. The long term renal outcome was not associated with age, sex, severity of proteinuria, class of LN or initial renal function. Patients who achieved remission at 6 months had a good long-term outcome. The demographic and clinical features of WHO class III and IV LN in Sri Lankan patients were similar to that reported in the global literature. 75% of patients responded to the Euro-lupus regimen. Therefore, this regime is a suitable initial regimen for LN patients in SL. Good long-term renal outcome can be predicted by early response to therapy. Further studies are necessary to explore better treatment options for patients who fail to achieve remission during initial therapy.

Health related quality of life in Mexican women with systemic lupus erythematosus: a descriptive study using SF-36 and LupusQoL(C).

PubMed

García-Carrasco, M; Mendoza-Pinto, C; Cardiel, M H; Méndez-Martínez, S; García-Villaseñor, A; Jiménez-Hernández, C; Alonso-García, N E; Briones-Rojas, R; Ramos-Álvarez, G; López-Colombo, A

2012-10-01

The LupusQoL© questionnaire is a disease-specific health related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The Short Form-36 (SF-36) is a generic instrument that captures the physical, psychological, and social impact. We conducted a descriptive study of women aged ≥ 18 years attending our Lupus Clinic. HRQOL was assessed by applying the LupusQoL© and SF-36. Lupus activity was measured using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed using descriptive statistics, the chi-square test and Pearson's product moment correlation coefficient. A total of 127 patients were included with a mean age of 40.5 ± 12.6 years. The mean disease duration was 8.2 ± 5.6 years, the mean disease activity score was 2.4 ± 3.0, and the mean SDI score 0.77 ± 1.06. The mean SF-36 score was 58.1 ± 21.1 and the mean LupusQoL© score was 69 ± 22.7. The correlation between global scores of the SF-36 and LupusQoL© was rho = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36 and the LupusQoL© was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively. The correlation between the SDI and the SF-36 and the LupusQoL© was -0.28 (p = 0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL© and SF-36 were useful instruments in assessing HRQOL in Mexican lupus female patients. The usefulness of the LupusQoL© should be evaluated in lupus patients with moderate to severe disease activity.

Seizure disorders in Systemic Lupus Erythematosus

PubMed Central

Hanly, John G.; Urowitz, Murray B.; Su, Li; Gordon, Caroline; Bae, Sang-Cheol; Sanchez-Guerrero, Jorge; Romero-Diaz, Juanita; Wallace, Daniel J; Clarke, Ann E.; Ginzler, E.M.; Merrill, Joan T.; Isenberg, David A.; Rahman, Anisur; Petri, M.; Fortin, Paul R.; Gladman, D. D.; Bruce, Ian N.; Steinsson, Kristjan; Dooley, M.A.; Khamashta, Munther A.; Alarcón, Graciela S.; Fessler, Barri J.; Ramsey-Goldman, Rosalind; Manzi, Susan; Zoma, Asad A.; Sturfelt, Gunnar K.; Nived, Ola; Aranow, Cynthia; Mackay, Meggan; Ramos-Casals, Manuel; van Vollenhoven, R.F.; Kalunian, Kenneth C.; Ruiz-Irastorza, Guillermo; Lim, Sam; Kamen, Diane L.; Peschken, Christine A.; Inanc, Murat; Theriault, Chris; Thompson, Kara; Farewell, Vernon

2015-01-01

Objective To describe the frequency, attribution, outcome and predictors of seizures in SLE Methods The Systemic Lupus International Collaborating Clinics (SLICC) performed a prospective inception cohort study. Demographic variables, global SLE disease activity (SLEDAI-2K), cumulative organ damage (SLICC/ACR Damage Index (SDI)) and neuropsychiatric events were recorded at enrollment and annually. Lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor antibodies were measured at enrollment. Physician outcomes of seizures were recorded. Patient outcomes were derived from the SF-36 mental (MCS) and physical (PCS) component summary scores. Statistical analyses included Cox and linear regressions. Results The cohort was 89.4% female with a mean follow up of 3.5±2.9 years. 75/1631 (4.6%) had ≥1 seizure, the majority around the time of SLE diagnosis. Multivariate analysis indicated a higher risk of seizures with African race/ethnicity (HR(CI):1.97 (1.07–3.63); p=0.03) and lower education status (1.97 (1.21–3.19); p<0.01). Higher damage scores (without NP variables) were associated with an increased risk of subsequent seizures (SDI=1:3.93 (1.46–10.55)); SDI=2 or 3:1.57 (0.32–7.65); SDI≥4:7.86 (0.89–69.06); p=0.03). There was an association with disease activity but not with autoantibodies. Seizures attributed to SLE frequently resolved (59/78(76%)) in the absence of anti-seizure drugs. There was no significant impact on the MCS or PCS scores. Anti-malarial drugs in absence of immunosuppressive agents were associated with reduced seizure risk (0.07(0.01–0.66); p=0.03). Conclusion Seizures occurred close to SLE diagnosis, in patients with African race/ethnicity, lower educational status and cumulative organ damage. Most seizures resolved without a negative impact on health-related quality of life. Anti-malarial drugs were associated with a protective effect. PMID:22492779

Predictors of non-response and non-compliance in African American lupus patients: Findings from the Balancing Lupus Experiences with Stress Strategies (BLESS) Study.

PubMed

Williams, Edith M; Zhang, Jiajia; Zhou, Jie; Kamen, Diane; Oates, James C

2014-02-01

Arthritis self-management education has demonstrated significant improvements in health distress, self-reported global health, and activity limitation, with trends toward improvement in self efficacy and mental stress management. Consequently, numerous national agencies have recommended arthritis self-management education to complement medical care. Despite these recommendations, arthritis self-management education has reached only a limited number of people. Compliance is also a persistent problem in standardized programs. As part of the Balancing Lupus Experiences with Stress Strategies (BLESS) Study, a validated psychosocial stress intervention was piloted among a cohort of African American lupus patients participating in an SLE database project at the Medical University of South Carolina (MUSC). Recruitment attempts were made with the 330 database participants who met eligibility requirements for the study. While enrollment was limited to 30 participants (n=15 controls and n=15 intervention), two of the participants assigned to the intervention group did not attend any intervention sessions and several participants did not complete post-intervention questionnaires. Therefore, data were analyzed on 30 participants at baseline, 25 (n=13 controls and n=12 intervention) at post-intervention, and 22 (n=12 controls and n=10 intervention) at four months post-intervention. In an effort to characterize those who fully participated in the study and those who were non-compliant or non-responsive to recruitment attempts, we obtained descriptive data from African-American Lupus patients participating in the SLE Clinic Database Project. This information can be used to develop and refine future intervention activities.

Effect of long-term hydroxychloroquine on vascular events in patients with systemic lupus erythematosus: a database prospective cohort study.

PubMed

Hsu, Chung-Yuan; Lin, Yu-Sheng; Su, Yu-Jih; Lin, Hsing-Fen; Lin, Ming-Shyan; Syu, Ya-Jhu; Cheng, Tien-Tsai; Yu, Shan-Fu; Chen, Jia-Feng; Chen, Tien-Hsing

2017-12-01

The incidence of thromboembolism in patients with SLE is higher than that in the general population. HCQ, widely used to treat lupus, may have vascular protective effects. The aim of this study was to determine whether long-term HCQ exposure is associated with decreased thromboembolism risk in SLE. We designed a prospective cohort study within an SLE population based on the National Health Insurance Research Database in Taiwan. We divided participants into HCQ and control groups according to HCQ prescription during the first year. These groups were defined by medication possession ratio (MPR) ⩾80% and MPR = 0%, respectively. Patients with an MPR between 0 and 80% were excluded. The primary outcome was a composite vascular event, including acute coronary syndrome, ischaemic stroke, pulmonary embolism, deep vein thrombosis and peripheral arterial disease 1 year after inclusion. We excluded patients from the cohort if they had outcomes within the first year. A total of 8397 patients were eligible for analysis. After propensity-score matching, we included 1946 patients in each group. During a mean follow-up of 7.4 years, the number of events was 139 in the HCQ group (7.1%) and 149 in the control group (7.7%). The risk of vascular events in the HCQ group was similar to that in the control group (hazard ratio = 0.91; 95% CI: 0.72, 1.15). Further subgroup analyses confirmed no statistically significant differences between the groups. Long-term HCQ appears to have no vascular protective effect in patients with SLE. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

THE CAROLINA LUPUS STUDY (CLU)

EPA Science Inventory

Carolina Lupus (CLU) Study, an epidemiologic study of risk factors for systemic lupus erythematosus (SLE). SLE is a severe, chronic, systemic autoimmune disease that disproportionately affects women and African-Americans. The CLU Study focuses on measures of endogenous hormone ex...

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

PubMed

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2�

Psychometric structure of the Chinese Multiethnic Adolescent Cultural Identity Questionnaire.

PubMed

Hu, Fa-Wen; Wang, Pei; Li, Li-Ju

2014-12-01

In this study, we used the Chinese Multiethnic Adolescent Cultural Identity Questionnaire (CMACIQ) and collected valid data from 1,036 participants to systematically examine the mental model of cultural identity in Chinese multiethnic adolescents. Exploratory factor analysis and structural equation modeling were performed on the data to discover the factor structure and dimensions of cultural identity. The psychometric properties of the scale were rigorously validated in 2,744 new multiethnic participants from 5 native ethnic groups in Yunnan province in China. The results indicated that CMACIQ had reasonable metric properties and good fit indices. The hierarchical model of cultural identity consisted of 2 second-order factors, Ethnic Cultural Identity and Mainstream Cultural Identity in School. The first higher order factor was composed of preference for ethnic things, ethnic acceptance, religious belief, and ethnic convention, while the second comprised 2 first-order factors, Social Norms and Dominant Culture. The potential application and limitations of CMACIQ are discussed. (c) 2014 APA, all rights reserved.

A rare case of unilateral discoid lupus erythematosus mimicking lupus vulgaris.

PubMed

Verma, Parul; Pathania, Sucheta; Kubba, Asha

2017-11-08

Discoidlupus erythematosus (DLE) is a chronic type of cutaneous lupus erythematosus which can present in various morphologies, and the diagnosis can be rather confounding. Prompt evaluation and treatment is necessary to prevent disfigurement and systemic involvement associated with DLE. The following case presented a diagnostic dilemma as the lesion mimicked lupus vulgaris. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Apolipoprotein H promoter polymorphisms in relation to lupus and lupus-related phenotypes.

PubMed

Suresh, Sangita; Demirci, F Yesim K; Jacobs, Erin; Kao, Amy H; Rhew, Elisa Y; Sanghera, Dharambir K; Selzer, Faith; Sutton-Tyrrell, Kim; McPherson, David; Bontempo, Franklin A; Kammerer, Candace M; Ramsey-Goldman, Rosalind; Manzi, Susan; Kamboh, M Ilyas

2009-02-01

Sequence variation in gene promoters is often associated with disease risk. We tested the hypothesis that common promoter variation in the APOH gene (encoding for ss(2)-glycoprotein I) is associated with systemic lupus erythematosus (SLE) risk and SLE-related clinical phenotypes in a Caucasian cohort. We used a case-control design and genotyped 345 women with SLE and 454 healthy control women for 8 APOH promoter single-nucleotide polymorphisms (SNP; -1284C>G, -1219G>A, -1190G>C, -759A>G, -700C>A, -643T>C, -38G>A, and -32C>A).Association analyses were performed on single SNP and haplotypes. Haplotype analyses were performed using EH (Estimate Haplotype-frequencies) and Haploview programs. In vitro reporter gene assay was performed in COS-1 cells. Electrophoretic mobility shift assay (EMSA) was performed using HepG2 nuclear cells. Overall haplotype distribution of the APOH promoter SNP was significantly different between cases and controls (p = 0.009). The -643C allele was found to be protective against carotid plaque formation (adjusted OR 0.37, p = 0.013) among patients with SLE. The -643C allele was associated with a ~2-fold decrease in promoter activity as compared to wild-type -643T allele (mean +/- standard deviation: 3.94 +/- 0.05 vs 6.99 +/- 0.68, p = 0.016). EMSA showed that the -643T>C SNP harbors a binding site for a nuclear factor. The -1219G>A SNP showed a significant association with the risk of lupus nephritis (age-adjusted OR 0.36, p = 0.016). Our data indicate that APOH promoter variants may be involved in the etiology of SLE, especially the risk for autoimmune-mediated cardiovascular disease.

Medicare Utilization and Expenditures Around Incident Dementia in a Multiethnic Cohort.

PubMed

Zhu, Carolyn W; Cosentino, Stephanie; Ornstein, Katherine; Gu, Yian; Scarmeas, Nikolaos; Andrews, Howard; Stern, Yaakov

2015-11-01

Few studies have examined patterns of health care utilization and costs during the period around incident dementia. Participants were drawn from the Washington Heights-Inwood Columbia Aging Project, a multiethnic, population-based, prospective study of cognitive aging of Medicare beneficiaries in a geographically defined area of northern Manhattan. Medicare utilization and expenditure were examined in individuals with clinically diagnosed dementia from 2 years before until 2 years after the initial diagnosis. A sample of non-demented individuals who were matched on socio-demographic and clinical characteristics at study enrollment was used as controls. Multivariable regression analysis estimated effects on Medicare utilization and expenditures associated with incident dementia. During the 2 years before incident dementia, rates of inpatient admissions and outpatient visits were similar between dementia patients and non-demented controls, but use of home health and skilled nursing care and durable medical equipment were already higher in dementia patients. Results showed a small but significant excess increase associated with incident dementia in inpatient admissions but not in other areas of care. In the 2 years before incident dementia, total Medicare expenditures were already higher in dementia patients than in non-demented controls. But we found no excess increases in Medicare expenditures associated with incident dementia. Demand for medical care already is increasing and costs are higher at the time of incident dementia. There was a small but significant excess risk of inpatient admission associated with incident dementia. Published by Oxford University Press on behalf of the Gerontological Society of America 2015.

Epstein-Barr virus infection induces lupus autoimmunity.

PubMed

Harley, John B; James, Judith A

2006-01-01

Systemic lupus erythematosus (SLE or lupus) is a systemic autoimmune disease characterized by a constellation of varied clinical presentations, although the nearly universal presence of autoantibodies is a salient unifying feature. Ongoing research efforts focus on understanding the complex combination of genetic and environmental factors that lead to SLE in select individuals. Our previous work has demonstrated that years before diagnosis abnormal autoantibody responses are present in the sera of patients who will subsequently develop lupus and, further, that the initial targets of two of these key responses (anti-Sm B' and anti-60 kD Ro alone) have been identified for some patients. Indeed, our results suggest that the first lupus-specific autoantibodies arise from particular antibodies directed against Epstein-Barr virus Nuclear Antigen-1 (EBNA-1) and that infection with Epstein-Barr virus (EBV) is an environmental risk factor for lupus. The predicted sequence of events is normal immunity, followed by Epstein- Barr virus infection, the generation of anti-EBNA-1 antibodies, then followed by those particular anti-EBNA-1 antibodies that also bind lupus-specific autoantigens (Sm or Ro), followed by the development of more complex autoimmune responses, and, finally, culminating in clinical disease. Studies from others and those underway suggest that lupus patients have unusual immune responses to Epstein-Barr virus. In aggregate, these results are consistent with an immune response against Epstein-Barr virus being important in at least some patients for the initiation of lupus autoimmunity.

What People with Lupus Need to Know about Osteoporosis

MedlinePlus

... Need to Know About Osteoporosis What People With Lupus Need to Know About Osteoporosis What Is Lupus? Lupus is an autoimmune disease, a disorder in ... new habits for healthy bones. The Link Between Lupus and Osteoporosis Studies have found an increase in ...

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

Development Education and Multi-Ethnic Education: Some Tensions. Development Education Paper No. 21.

ERIC Educational Resources Information Center

Storm, Michael

The document examines the relationships between multi-ethnic and development education in Great Britain. Multi-ethnic education, initially with a national focus, has a global dimension, and development education, initially with a global focus, has a national and even local dimension. A common interest in human diversity and human inequalities…

Dietary choline and betaine intakes vary in an adult multiethnic population.

PubMed

Yonemori, Kim M; Lim, Unhee; Koga, Karin R; Wilkens, Lynne R; Au, Donna; Boushey, Carol J; Le Marchand, Loïc; Kolonel, Laurence N; Murphy, Suzanne P

2013-06-01

Choline and betaine are important nutrients for human health, but reference food composition databases for these nutrients became available only recently. We tested the feasibility of using these databases to estimate dietary choline and betaine intakes among ethnically diverse adults who participated in the Multiethnic Cohort (MEC) Study. Of the food items (n = 965) used to quantify intakes for the MEC FFQ, 189 items were exactly matched with items in the USDA Database for the Choline Content of Common Foods for total choline, choline-containing compounds, and betaine, and 547 items were matched to the USDA National Nutrient Database for Standard Reference for total choline (n = 547) and 148 for betaine. When a match was not found, choline and betaine values were imputed based on the same food with a different form (124 food items for choline, 300 for choline compounds, 236 for betaine), a similar food (n = 98, 284, and 227, respectively) or the closest item in the same food category (n = 6, 191, and 157, respectively), or the values were assumed to be zero (n = 1, 1, and 8, respectively). The resulting mean intake estimates for choline and betaine among 188,147 MEC participants (aged 45-75) varied by sex (372 and 154 mg/d in men, 304 and 128 mg/d in women, respectively; P-heterogeneity < 0.0001) and by race/ethnicity among Caucasians, African Americans, Japanese Americans, Latinos, and Native Hawaiians (P-heterogeneity < 0.0001), largely due to the variation in energy intake. Our findings demonstrate the feasibility of assessing choline and betaine intake and characterize the variation in intake that exists in a multiethnic population.

Antiphospholipid antibodies and non-thrombotic manifestations of systemic lupus erythematosus.

PubMed

İlgen, U; Yayla, M E; Ateş, A; Okatan, İ E; Yurteri, E U; Torgutalp, M; Keleşoğlu, A B D; Turgay, T M; Kınıklı, G

2018-04-01

Objectives The aim of this study was to investigate the association between antiphospholipid antibodies and non-thrombotic and non-gestational manifestations of systemic lupus erythematosus. Methods Systemic lupus erythematosus patients with persistently positive antiphospholipid antibodies or lupus anticoagulant were identified and grouped as systemic lupus erythematosus with antiphospholipid syndrome (SLE-APS), systemic lupus erythematosus with positive antiphospholipid antibodies/lupus anticoagulant without antiphospholipid syndrome (SLE-aPL), and systemic lupus erythematosus with negative aPLs (SLE-No aPL). Groups were compared in terms of non-thrombotic systemic lupus erythematosus manifestations and laboratory features retrospectively. Results A total of 150 systemic lupus erythematosus patients, 26 with SLE-APS, 25 with SLE-aPL, and 99 with SLE-No aPL, were identified. Livedo reticularis, neurologic involvement, and thrombocytopenia were more common in antiphospholipid antibody positive systemic lupus erythematosus cases. Malar rash, arthritis, and pleuritis were more common in the SLE-No aPL, SLE-APS, and SLE-aPL groups, respectively. Positivity rates and titers of specific antiphospholipid antibodies did not differ between the SLE-APS and SLE-aPL groups. Conclusions Presence of antiphospholipid syndrome or persistent antiphospholipid antibodies may be related to non-thrombotic and non-gestational systemic lupus erythematosus manifestations. Patients with systemic lupus erythematosus plus antiphospholipid syndrome and persistent antiphospholipid antibodies without antiphospholipid syndrome also differ in terms of systemic lupus erythematosus manifestations.

Definition and initial validation of a Lupus Low Disease Activity State (LLDAS).

PubMed

Franklyn, Kate; Lau, Chak Sing; Navarra, Sandra V; Louthrenoo, Worawit; Lateef, Aisha; Hamijoyo, Laniyati; Wahono, C Singgih; Chen, Shun Le; Jin, Ou; Morton, Susan; Hoi, Alberta; Huq, Molla; Nikpour, Mandana; Morand, Eric F

2016-09-01

Treating to low disease activity is routine in rheumatoid arthritis, but no comparable goal has been defined for systemic lupus erythematosus (SLE). We sought to define and validate a Lupus Low Disease Activity State (LLDAS). A consensus definition of LLDAS was generated using Delphi and nominal group techniques. Criterion validity was determined by measuring the ability of LLDAS attainment, in a single-centre SLE cohort, to predict non-accrual of irreversible organ damage, measured using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Consensus methodology led to the following definition of LLDAS: (1) SLE Disease Activity Index (SLEDAI)-2K ≤4, with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever) and no haemolytic anaemia or gastrointestinal activity; (2) no new lupus disease activity compared with the previous assessment; (3) a Safety of Estrogens in Lupus Erythematosus National Assessment (SELENA)-SLEDAI physician global assessment (scale 0-3) ≤1; (4) a current prednisolone (or equivalent) dose ≤7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents. Achievement of LLDAS was determined in 191 patients followed for a mean of 3.9 years. Patients who spent greater than 50% of their observed time in LLDAS had significantly reduced organ damage accrual compared with patients who spent less than 50% of their time in LLDAS (p=0.0007) and were significantly less likely to have an increase in SDI of ≥1 (relative risk 0.47, 95% CI 0.28 to 0.79, p=0.005). A definition of LLDAS has been generated, and preliminary validation demonstrates its attainment to be associated with improved outcomes in SLE. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Validation of the LupusPRO version 1.8: an update to a disease-specific patient-reported outcome tool for systemic lupus erythematosus.

PubMed

Azizoddin, D R; Weinberg, S; Gandhi, N; Arora, S; Block, J A; Sequeira, W; Jolly, M

2018-04-01

Objectives LupusPRO has shown good measurement properties as a disease-specific patient-reported outcome tool in systemic lupus erythematosus (SLE). For the purpose of clinical trials, the version 1.7 (v1.7) domain of Pain-Vitality was separated into distinct Pain, Vitality and Sleep domains in v1.8, and the psychometric properties examined. Methods A total of 131 consecutive SLE patients were self-administered surveys assessing fatigue (FACIT, SF-36), pain (Pain Inventory, SF-36), insomnia (Insomnia Severity Index), emotional health (PHQ-9, SF-36) and quality of life (SF-36, LupusPRO) at routine care visits. Internal consistency reliability (ICR) for each domain was obtained using Cronbach's alpha. The convergent construct validity of LupusPRO domains with corresponding SF-36 domains or tools were tested using Spearman correlation. Varimax rotations were conducted to assess factor structures of the LupusPRO v1.8. Results Mean (SD) age was 40.04 (14.10) years. Scores from the LupusPRO-Sleep domain strongly correlated with insomnia scores, while LupusPRO-Vitality correlated strongly with fatigue (FACIT) and SF-36 vitality. The LupusPRO-Pain domain correlated strongly with pain (SF36 Bodily-Pain, Pain Inventory) scores. Similarly, the LupusPRO domains of Physical and Emotional Health had significant correlations with corresponding SF-36 domains. The ICR for HRQoL and non-HRQoL were 0.96 and 0.81. LupusPRO (domains HRQoL and QoL) scores correlated with disease activity. Principal component analysis included seven factor loadings presenting for the HRQOL subscales (combined Sleep, Vitality, and Pain), and three factors for the NHRQoL (Combined Coping and Social Support). Conclusions LupusPRO v1.8 (including its Sleep, Vitality, and Pain domains) has acceptable reliability and validity. Use of LupusPRO as an outcome measure in clinical trials would facilitate responsiveness assessment.

Initial digital vasculitis in a large multicenter cohort of childhood-onset systemic lupus erythematosus.

PubMed

Sakamoto, Ana Paula; Silva, Clovis Artur; Silva, Marco Felipe Castro da; Lopes, Anandreia Simões; Russo, Gleice Clemente Souza; Sallum, Adriana Maluf Elias; Kozu, Katia; Bonfá, Eloisa; Saad-Magalhães, Claudia; Pereira, Rosa Maria Rodrigues; Len, Claudio Arnaldo; Terreri, Maria Teresa

To assess clinical digital vasculitis (DV) as an initial manifestation of childhood-onset systemic lupus erythematosus (cSLE) within a large population. Multicenter cross-sectional study including 852 cSLE patients (ACR criteria) followed in ten Pediatric Rheumatology centers in São Paulo State, Brazil. DV was observed in 25/852 (3%) cSLE patients. Periungual hemorrhage was diagnosed in 12 (48%), periungual infarction in 7 (28%), tip finger ulceration in 4 (16%), painful nodules in 1 (4%) and gangrene in 1 (4%). A poor outcome, with digital resorption, occurred in 5 (20%). Comparison of patients with and without DV revealed higher frequency of malar rash (80% vs. 53%, p=0.008), discoid rash (16% vs. 4%, p=0.017), photosensitivity (76% vs. 45%, p=0.002) and other cutaneous vasculitides (80% vs. 19%, p<0.0001), whereas the frequency of overall constitutional features (32% vs. 61%, p=0.003), fever (32% vs. 56%, p=0.020) and hepatomegaly (4% vs. 23%, p=0.026) were lower in these patients. Frequency of female gender, severe multi-organ involvement, autoantibodies profile and low complement were alike in both groups (p>0.05). SLEDAI-2K median, DV descriptor excluded, was significantly lower in patients with DV compared to those without this manifestation [10 (0-28) vs. 14 (0-58), p=0.004]. Visceral vasculitis or death were not observed in this cSLE cohort. The frequency of cyclophosphamide use (0% vs. 18%, p=0.014) was significantly lower in the DV group. Our large multicenter study identified clinical DV as one of the rare initial manifestation of active cSLE associated with a mild multisystemic disease, in spite of digital resorption in some of these patients. Copyright © 2017. Published by Elsevier Editora Ltda.

Dyslipidemia in systemic lupus erythematosus: just another comorbidity?

PubMed

Tselios, Konstantinos; Koumaras, Charalambos; Gladman, Dafna D; Urowitz, Murray B

2016-04-01

Among traditional atherosclerotic risk factors, dyslipidemia is believed to decisively affect the long-term prognosis of lupus patients, not only with regard to cardiovascular events but also by influencing other manifestations, such as lupus nephritis. The aim of this study was to review the epidemiology, pathogenesis, evidence for its impact on atherosclerosis manifestations and management of dyslipidemia in lupus patients. English-restricted MEDLINE database search (Medical Subject Headings: lupus or systemic lupus erythematosus and dyslipidemia or hyperlipidemia). The prevalence of dyslipidemia in systemic lupus erythematosus (SLE) ranges from 36% at diagnosis to 60% or even higher after 3 years, depending on definition. Multiple pathogenetic mechanisms are implicated, including antibodies against lipoprotein lipase and cytokines affecting the balance between pro- and anti-atherogenic lipoproteins. Dyslipidemia has a clear impact on clinical cardiovascular disease and surrogate markers for subclinical atherosclerosis. Moreover, it negatively affects end-organ damage (kidneys and brain). Treatment with statins yielded contradictory results as per minimizing cardiovascular risk. Dyslipidemia is a significant comorbidity of lupus patients with multiple negative effects in the long term. Its treatment represents a modifiable risk factor; prompt and adequate treatment can minimize unnecessary burden in lupus patients, thus reducing hospitalizations and their overall morbidity and mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

Clinical predictors of fetal and maternal outcome in systemic lupus erythematosus: a prospective study of 103 pregnancies.

PubMed

Cortés-Hernández, J; Ordi-Ros, J; Paredes, F; Casellas, M; Castillo, F; Vilardell-Tarres, M

2002-06-01

Our aim was to assess the outcome of pregnancy in a cohort of patients with SLE and to evaluate clinical and laboratory markers for fetal outcome and maternal flares. Sixty patients with 103 pregnancies were evaluated prospectively between 1984 and 1999. There were 68 live births, 15 spontaneous abortions, 12 stillbirths and eight therapeutic abortions. Of liveborn infant births, 19 were premature, 24 had suffered intrauterine growth restriction and one had neonatal lupus. Maternal lupus flares occurred in 33% of pregnancies, mostly in the second trimester (26%) and in the post-partum period (51%). Flares during pregnancy showed a statistically significant association with discontinuation of chloroquine treatment, a history of more than three flares before gestation, and a SLEDAI (Systemic Lupus Erythematosus Disease Activity Index) score of >or=5 in these flares. Antiphospholipid antibodies, C3 hypocomplementaemia and hypertension during pregnancy were significantly associated with fetal loss, prematurity and intrauterine growth restriction. Patients with more active SLE and those with aPL antibodies and hypertension should be monitored and managed carefully during pregnancy.

How Does Lupus Affect the Blood?

MedlinePlus

... Up for Our Newsletter Donate Share on Twitter Facebook Pinterest Email Print How lupus affects the blood Lupus Foundation of America October 17, 2017 Dr. Michael Rosove Resource Content Blood is made ...

Risk of autism spectrum disorder in children born to mothers with systemic lupus erythematosus and rheumatoid arthritis in Taiwan.

PubMed

Tsai, Ping-Han; Yu, Kuang-Hui; Chou, I-Jun; Luo, Shue-Fen; Tseng, Wen-Yi; Huang, Lu-Hsiang; Kuo, Chang-Fu

2017-11-26

To determine whether offspring of Taiwanese mothers with systemic lupus erythematosus or rheumatoid arthritis have a higher risk of autism spectrum disorder. Using the National Health Insurance database and National Birth Registry, we identified a cohort of all live births in Taiwan between 2001 and 2012. Children born to mothers with systemic lupus erythematosus or rheumatoid arthritis were identified and matched with up to 8 controls by maternal age, 1-minute Apgar score, 5-minute Apgar score, mode of delivery, sex of the child, gestational age, birth weight and place of residence. Marginal Cox proportional hazard models were used to estimate relative risk (RR) with 95% confidence intervals (CI) for ASD in offspring. Of 1,893,244 newborns, 0.08% (n=1594) were born to systemic lupus erythematosus mothers, and 0.04% (n=673) were born to rheumatoid arthritis mothers. Overall, 5 of 673 (0.74%) offspring of rheumatoid arthritis mothers, 7 of 1594 (0.44%) offspring of systemic lupus erythematosus mothers and 10,631 of 1,893,244 (0.56%) offspring of all mothers developed autism spectrum disorder. Autism spectrum disorder incidence (per 100,000 person-years) was 140.39 (95% CI, 45.58-327.62) for the rheumatoid arthritis group and 76.19 (95% CI, 30.63-156.97) for the systemic lupus erythematosus group. Autism spectrum disorder risk was not significantly higher for children born to mothers with rheumatoid arthritis (HR, 1.42; 95% CI, 0.60-3.40) or systemic lupus erythematosus (HR, 0.76; 95% CI, 0.36-1.59). Children born to women with systemic lupus erythematosus or rheumatoid arthritis do not have a higher risk of autism spectrum disorder. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Treatment of coexistent psoriasis and lupus erythematosus.

PubMed

Varada, Sowmya; Gottlieb, Alice B; Merola, Joseph F; Saraiya, Ami R; Tintle, Suzanne J

2015-02-01

The coexistence of psoriasis and lupus erythematosus (LE) is rare. Anecdotal evidence suggests that anti-tumor necrosis factor alfa (TNF-α) agents may be efficacious in LE, although their use is commonly avoided in this disease because of concern for lupus flare. We sought to describe the epidemiology, serologic findings, and therapeutic choices in patients with coexistent psoriasis/psoriatic arthritis and LE and to determine the risk of lupus flares with TNF-α inhibitors. We performed a retrospective multicenter study of patients given the diagnoses of psoriasis (or psoriatic arthritis) and lupus erythematosus (systemic LE or cutaneous LE, including either subacute cutaneous LE or discoid LE) at 2 academic tertiary-care centers. A total of 96 patients with a mean age of 56 years was included. We report higher-than-expected rates of white race and psoriatic arthritis. One clinical lupus flare was observed in a patient receiving a TNF-α inhibitor, resulting in an incidence of 0.92% lupus flares per patient-year of TNF-α inhibitor use. Retrospective chart review, small sample size, and limited documentation. Anti-TNF-α agents, ustekinumab, and abatacept may be valid treatment options for patients with concomitant LE and psoriasis. Clinical lupus flares in LE patients treated with TNF-α inhibitors were infrequent. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study.

PubMed

Lai, Kah Nyin; Ho, Weang Kee; Kang, In Nee; Kang, Peter Choon Eng; Phuah, Sze Yee; Mariapun, Shivaani; Yip, Cheng-Har; Mohd Taib, Nur Aishah; Teo, Soo-Hwang

2017-02-22

Genetic testing for BRCA1 and BRCA2 has led to the accurate identification of individuals at higher risk of cancer and the development of new therapies. Approximately 10-20% of the genetic testing for BRCA1 and BRCA2 leads to the identification of variants of uncertain significance (VUS), with higher proportions in Asians. We investigated the functional significance of 7 BRCA1 and 25 BRCA2 variants in a multi-ethnic Asian cohort using a case-control approach. The MassARRAY genotyping was conducted in 1,394 Chinese, 406 Malay and 310 Indian breast cancer cases and 1,071 Chinese, 167 Malay and 255 Indian healthy controls. The association of individual variant with breast cancer risk was analyzed using logistic regression model adjusted for ethnicity, age and family history. Our study confirmed BRCA2 p.Ile3412Val is presented in >2% of unaffected women and is likely benign, and BRCA2 p.Ala1996Thr which is predicted to be likely pathogenic by in-silico models is presented in 2% of healthy Indian women suggesting that it may not be associated with breast cancer risk. Single-variant analysis suggests that BRCA1 p.Arg762Ser may be associated with breast cancer risk (OR = 7.4; 95% CI, 0.9-62.3; p = 0.06). Our study shows that BRCA2 p.Ile3412Val and p.Ala1996Thr are likely benign and highlights the need for population-specific studies to determine the likely functional significance of population-specific variants. Our study also suggests that BRCA1 p.Arg762Ser may be associated with increased risk of breast cancer but other methods or larger studies are required to determine a more precise estimate of breast cancer risk.

A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus

PubMed Central

Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D

2017-01-01

Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11–23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little

A randomized, open-label study to investigate the effect of belimumab on pneumococcal vaccination in patients with active, autoantibody-positive systemic lupus erythematosus.

PubMed

Chatham, W; Chadha, A; Fettiplace, J; Kleoudis, C; Bass, D; Roth, D; Gordon, D

2017-12-01

Objective Intravenous belimumab 10 mg/kg is approved as an add-on therapy in patients with active, autoantibody-positive systemic lupus erythematosus. This study aimed to assess the impact of belimumab on immune response to pneumococcal vaccination in patients with systemic lupus erythematosus. Methods This was a Phase 4, open-label study (GSK BEL115470; NCT01597492) conducted in the United States. Patients were randomized (7:9) to receive a 23-valent pneumococcal vaccination four weeks prior to (pre-belimumab cohort) or 24 weeks after (belimumab-concurrent cohort) commencing four-weekly belimumab 10 mg/kg intravenous treatment plus standard systemic lupus erythematosus therapy. Analyses of vaccine titers were performed on the as-treated population (received ≥1 dose of belimumab). The primary endpoint was the proportion of patients with positive antibody responses (≥2-fold increase from pre-vaccination levels, or post-vaccination level ≥ 0.6 µg/mL if pre-vaccination levels were unquantifiable) to ≥1 of 23 pneumococcal vaccine serotypes, four weeks post vaccination. Other endpoints included the proportion of patients with positive antibody responses to ≥2 to ≥10, and ≥11-23 (post hoc analysis) of serotypes. Safety was assessed by monitoring adverse events. Results Seventy-nine patients received pneumococcal vaccination (pre-belimumab cohort, n = 34; belimumab-concurrent cohort, n = 45). The majority (87.3% [69/79]) completed the study; 10 (12.7%) withdrew (patient request, n = 3; adverse event, n = 3; lost to follow-up, n = 2; other, n = 2). At Week 4 post-vaccination, 97.0% (32/33) and 97.6% (40/41) of patients (pre-belimumab and concurrent belimumab cohorts, respectively) had a positive response to ≥1 of 23 pneumococcal serotypes. Over 85% of patients in both cohorts responded to ≥10 of serotypes, approximately 80% responded to ≥12 serotypes, and approximately two-thirds responded to ≥16 serotypes. Little

Prognostic factors for treatment response in patients with lupus nephritis.

PubMed

Miranda-Hernández, Dafhne; Cruz-Reyes, Claudia; Angeles, Ulises; Jara, Luis Javier; Saavedra, Miguel Angel

2014-01-01

To identify prognostic factors associated with response to induction therapy in lupus nephritis (LN) according to the stage of treatment. We analyzed a retrospective cohort of patients of systemic lupus erythematosus (SLE) with biopsy-proven LN from January 2001 to December 2008. LN was classified according to WHO. All patients received induction therapy and had a minimum follow-up period of two years. We analyzed 18 clinical and laboratory variables that potentially have predictive value for response to therapy. We identified predictors of therapeutic response at 6, 12 and 24 months by univariate and multivariate analysis; odds ratios (OR) with confidence intervals (CI) 95% were also calculated. We reviewed the clinical records of 168 patients, 141 female (84%). The response rate was 69% at 6 months, 86.9% at 12 months and 79.7% at 24 months. Multivariate analysis found that > 25 years of age at diagnosis of LN and the presence of microhematuria were factors associated with good response to induction treatment. At 12 months, baseline creatinine clearance < 30ml/min was associated with a poor response to treatment. Finally at 24 months, delay in treatment was a predictor of poor response to treatment and the presence of a histological proliferative NL and low C3 were associated with good response to treatment. There are treatment-modifiable factors that can alter aberrant immunologic activity of NF. Therefore, intensive early treatment of lupus nephritis is associated with favorable response to two years. Copyright © 2013 Elsevier España, S.L. All rights reserved.

The influence of energy standardisation on the alternate Mediterranean diet score and its association with mortality in the Multiethnic Cohort.

PubMed

Shvetsov, Yurii B; Harmon, Brook E; Ettienne, Reynolette; Wilkens, Lynne R; Le Marchand, Loic; Kolonel, Laurence N; Boushey, Carol J

2016-11-01

The alternate Mediterranean diet (aMED) score is an adaptation of the original Mediterranean diet score. Raw (aMED) and energy-standardised (aMED-e) versions have been used. How the diet scores and their association with health outcomes differ between the two versions is unclear. We examined differences in participants' total and component scores and compared the association of aMED and aMED-e with all-cause, CVD and cancer mortality. As part of the Multiethnic Cohort, 193 527 men and women aged 45-75 years from Hawaii and Los Angeles completed a baseline FFQ and were followed up for 13-18 years. The association of aMED and aMED-e with mortality was examined using Cox's regression, with adjustment for total energy intake. The correlation between aMED and aMED-e total scores was lower among people with higher BMI. Participants who were older, leaner, more educated and consumed less energy scored higher on aMED-e components compared with aMED, except for the red and processed meat and alcohol components. Men reporting more physical activity scored lower on most aMED-e components compared with aMED, whereas the opposite was observed for the meat component. Higher scores of both aMED and aMED-e were associated with lower risk of all-cause, CVD and cancer mortality. Although individuals may score differently with aMED and aMED-e, both scores show similar reductions in mortality risk for persons scoring high on the index scale. Either version can be used in studies of diet and mortality. Comparisons can be performed across studies using different versions of the score.

Law, Language, and the Multiethnic State.

ERIC Educational Resources Information Center

De Varennes, Fernand

1996-01-01

Examines why language policies should be considered in a multiethnic state and suggests that there are human rights issues that mandate some recognition of language demands and usage beyond what some states may provide. The article emphasizes that questions of language, ethnicity, and nationalism must be addressed in a rational and coherent…

Discrimination and Cumulative Disease Damage Among African American Women With Systemic Lupus Erythematosus.

PubMed

Chae, David H; Drenkard, Cristina M; Lewis, Tené T; Lim, S Sam

2015-10-01

We examined associations between unfair treatment, attributions of unfair treatment to racial discrimination, and cumulative disease damage among African American women with systemic lupus erythematosus (SLE). We used multivariable regression models to examine SLE damage among 578 African American women in metropolitan Atlanta, Georgia, recruited to the Georgians Organized Against Lupus cohort. When we controlled for demographic, socioeconomic, and health-related covariates, reporting any unfair treatment was associated with greater SLE damage compared with reporting no unfair treatment (b = 0.55; 95% confidence interval = 0.14, 0.97). In general, unfair treatment attributed to nonracial factors was more strongly associated with SLE damage than was unfair treatment attributed to racial discrimination, although the difference was not statistically significant. Unfair treatment may contribute to worse disease outcomes among African American women with SLE. Unfair treatment attributed to nonracial causes may have a more pronounced negative effect on SLE damage. Future research may further examine possible differences in the effect of unfair treatment by attribution.

Pregnancy and contraception in systemic and cutaneous lupus erythematosus.

PubMed

Guettrot-Imbert, G; Morel, N; Le Guern, V; Plu-Bureau, G; Frances, C; Costedoat-Chalumeau, N

2016-10-01

A causal link has long been described between estrogen and systemic lupus erythematosus activity. Contraceptive and pregnancy management is now common for lupus patients, but pregnancy continues to be associated with higher maternal and fetal mortality/morbidity in systemic lupus erythematosus patients than among the general population. Potential complications include lupus flares, obstetric complications (fetal loss, in utero growth retardation, premature birth) and neonatal lupus syndrome. Association with antiphospholipid antibodies or antiphospholipid syndrome increases the risk of obstetric complications. Anti-SSA and/or anti-SSB antibodies put fetuses at risk for neonatal lupus. Improving the outcome of such pregnancies depends upon optimal systematic planning of pregnancy at a preconception counseling visit coupled with a multidisciplinary approach. Absence of lupus activity, use of appropriate medication during pregnancy based on the patient's medical history and risk factors, and regular monitoring constitute the best tools for achieving a favorable outcome in such high-risk pregnancies. The aim of this review is to provide an update on the management of contraception and pregnancy in systemic lupus erythematosus, cutaneous lupus and/or antiphospholipid syndrome in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Environmental Exposures, Epigenetic Changes and the Risk of Lupus

PubMed Central

Somers, Emily C; Richardson, Bruce C

2013-01-01

A dose-dependent combination of environmental exposures, estrogenic hormones and genetic predisposition is thought to be required for lupus to develop and flare, but how the environment modifies the immune system in genetically predisposed people is unclear. Current evidence indicates that environmental agents that inhibit DNA methylation can convert normal antigen-specific CD4+ T lymphocytes into autoreactive, cytotoxic, pro-inflammatory cells that are sufficient to cause lupus-like autoimmunity in animal models, and that the same changes in DNA methylation characterize CD4+ T cells from patients with active lupus. Environmental agents implicated in inhibiting T cell DNA methylation include the lupus-inducing drugs procainamide and hydralazine, as well as diet, and agents causing oxidative stress, such as smoking, UV light exposure, and infections, which have been associated with lupus onset or disease activity. Other studies demonstrate that demethylated T cells cause only anti-DNA antibodies in mice lacking a genetic predisposition to lupus, but are sufficient to cause lupus-like autoimmunity in genetically predisposed mice and likely people, and that estrogens augment the disease. Collectively, these studies suggest that environmental agents that inhibit DNA methylation, together with lupus genes and estrogens or endocrine disruptors, combine in a dose-dependent fashion to cause lupus flares. PMID:24763540

Analysis of disease activity and response to treatment in a large Spanish cohort of patients with systemic lupus erythematosus.

PubMed

Pego-Reigosa, J M; Rúa-Figueroa, Í; López-Longo, F J; Galindo-Izquierdo, M; Calvo-Alén, J; Olivé-Marqués, A; del Campo, V; García-Yébenes, M J; Loza-Santamaría, E; Blanco, R; Melero-González, R; Vela-Casasempere, P; Otón-Sánchez, T; Tomero-Muriel, E; Uriarte-Isacelaya, E; Fito-Manteca, M C; Freire-González, M; Narváez, J; Fernández-Nebro, A; Zea-Mendoza, A; Rosas, J; Carlos Rosas, J

2015-06-01

The objectives of this paper are to study the impact of disease activity in a large cohort of patients with systemic lupus erythematosus (SLE) and estimate the rate of response to therapies. We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients. Data on demographics, disease characteristics: activity (SELENA-SLEDAI), damage, severity, hospitalizations and therapies were collected. Factors associated with refractory disease were identified by logistic regression. A total of 3658 patients (90% female; median SLE duration (interquartile range): 10.4 years (5.3-17.1)) were included. At the time of their last evaluation, 14.7% of the patients had moderate-severe SLE (SELENA-SLEDAI score ≥6). There were 1954 (53.4%) patients who were hospitalized for activity at least once over the course of the disease. At some stage, 84.6% and 78.8% of the patients received glucocorticoids and antimalarials, respectively, and 51.3% of the patients received at least one immunosuppressant. Owing to either toxicity or ineffectiveness, cyclophosphamide was withdrawn in 21.5% of the cases, mycophenolate mofetil in 24.9%, azathioprine in 40.2% and methotrexate in 46.8%. At some stage, 7.3% of the patients received at least one biologic. A total of 898 (24.5%) patients had refractory SLE at some stage. Renal, neuropsychiatric, vasculitic, hematological and musculoskeletal involvement, a younger age at diagnosis and male gender were associated with refractory disease. A significant percentage of patients have moderately-to-severely active SLE at some stage. Disease activity has a big impact in terms of need for treatment and cause of hospitalization. The effectiveness of the standard therapies for reducing disease activity is clearly insufficient. Some clinical features are associated with refractory SLE. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

The caregiver burden in lupus: findings from UNVEIL, a national online lupus survey in the United States.

PubMed

Al Sawah, S; Daly, R P; Foster, S A; Naegeli, A N; Benjamin, K; Doll, H; Bond, G; Moshkovich, O; Alarcón, G S

2017-01-01

Lupus imposes a substantial burden on patients; however, little is known about its impact on those caring for patients with the disease. In this study, we examined the impact 'caring for patients with lupus' has on caregivers from their own perspective. UNVEIL was a one-time online national cross-sectional survey developed in partnership with the Lupus Foundation of America and fielded targeting the US Lupus Foundation of America constituents in 2014. Eligible caregivers were adults who self-identified as unpaid caregivers of patients with lupus. Eligible caregivers had to complete a series of sociodemographic questions as well as a series of well established outcome measures, such as the Short Form 12v2 Health Survey, the Work Productivity and Activity Index, the Caregiver Burden Inventory, and the Perceived Benefits of Caregiving Scale. A total of 253 caregivers completed the survey. The majority of caregivers (90.1%) were aged 60 years or younger, more than half (54.2%) were men, and more than half (59.7%) identified themselves as either a spouse or a partner to the patient with lupus they were caring for. Overall health-related quality of life was close to the norm mean of the general US population. Caregivers who were employed missed an average of 12.8% of paid work time due to caregiving responsibilities and reported a 33.5% reduction in on-the-job effectiveness. Nearly half of the caregivers surveyed (49.4%) indicated that their caregiving responsibilities impacted their ability to socialize with friends, and almost all caregivers (97.6%) reported experiencing increased anxiety and stress in relation to their caregiving role. Caregiving for patients with lupus has a substantial impact on the work productivity and the social and emotional functioning of caregivers. Healthcare professionals and policymakers should continually assess the impact of healthcare decisions on the well-being of those caring for patients with lupus. © The Author(s) 2016.

Alveolar hemorrhage in systemic lupus erythematosus: a cohort review.

PubMed

Andrade, C; Mendonça, T; Farinha, F; Correia, J; Marinho, A; Almeida, I; Vasconcelos, C

2016-01-01

Diffuse alveolar hemorrhage (DAH) is a rare but potentially catastrophic manifestation with a high mortality. Among rheumatologic diseases, it occurs most frequently in patients with systemic lupus erythematosus (SLE) and systemic vasculitis. Despite new diagnostic tools and therapies, it remains a diagnostic and therapeutic challenge. The aim of this work was to characterize the SLE patients with an episode of alveolar hemorrhage followed in our Clinical Immunology Unit (CIU). A retrospective chart review was carried out for all patients with SLE followed in CIU between 1984 and the end of 2013. We reviewed the following data: demographic characteristics, clinical and laboratory data, radiologic investigations, histologic studies, treatment, and outcome. We identified 10 episodes of DAH, corresponding to seven patients, all female. These represent 1.6% of SLE patients followed in our Unit. The age at DAH attack was 42.75 ± 18.9 years. The average time between diagnosis of SLE and the onset of DAH was 7.1 years. Three patients had the diagnosis of SLE and the DAH attack at the same time. Disease activity according to SLEDAI was high, ranging from 15 to 41. All patients were treated with methylprednisolone, 37.5% cyclophosphamide and 28.6% plasmapheresis. The overall mortality rate was 28.6%. © The Author(s) 2015.

Neuropsychiatric Systemic Lupus Erythematosus

PubMed Central

Popescu, Alexandra; Kao, Amy H

2011-01-01

Neuropsychiatric systemic lupus erythematosus (NPSLE) is the least understood, yet perhaps the most prevalent manifestation of lupus. The pathogenesis of NPSLE is multifactorial and involves various inflammatory cytokines, autoantibodies, and immune complexes resulting in vasculopathic, cytotoxic and autoantibody-mediated neuronal injury. The management of NPSLE is multimodal and has not been subjected to rigorous study. Different treatment regimens include nonsteroidal anti-inflammatory drugs, anticoagulation, and immunosuppressives such as cyclophosphamide, azathioprine, mycophenolate mofetil, and methotrexate. For refractory NPSLE, intravenous immunoglobulin (IVIG), plasmapheresis, and rituximab have been used. Adjunctive symptomatic treatment complements these therapies by targeting mood disorders, psychosis, cognitive impairment, seizures or headaches. Several new biological agents are being tested including Belimumab, a human monoclonal antibody that targets B lymphocyte stimulator. This review focuses on the pathophysiology, treatment, and new potential therapies for neuropsychiatric manifestations of systemic lupus erythematosus. PMID:22379459

Changing patterns in clinical-histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis.

PubMed

Moroni, Gabriella; Vercelloni, Paolo Gilles; Quaglini, Silvana; Gatto, Mariele; Gianfreda, Davide; Sacchi, Lucia; Raffiotta, Francesca; Zen, Margherita; Costantini, Gloria; Urban, Maria Letizia; Pieruzzi, Federico; Messa, Piergiorgio; Vaglio, Augusto; Sinico, Renato Alberto; Doria, Andrea

2018-05-05

To evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time. We studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970-1985, P2 1986-2001 and P3 2002-2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test. A progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD. Clinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression

PubMed Central

Lu, Xiaoming; Zoller, Erin E.; Weirauch, Matthew T.; Wu, Zhiguo; Namjou, Bahram; Williams, Adrienne H.; Ziegler, Julie T.; Comeau, Mary E.; Marion, Miranda C.; Glenn, Stuart B.; Adler, Adam; Shen, Nan; Nath, Swapan K.; Stevens, Anne M.; Freedman, Barry I.; Tsao, Betty P.; Jacob, Chaim O.; Kamen, Diane L.; Brown, Elizabeth E.; Gilkeson, Gary S.; Alarcón, Graciela S.; Reveille, John D.; Anaya, Juan-Manuel; James, Judith A.; Sivils, Kathy L.; Criswell, Lindsey A.; Vilá, Luis M.; Alarcón-Riquelme, Marta E.; Petri, Michelle; Scofield, R. Hal; Kimberly, Robert P.; Ramsey-Goldman, Rosalind; Joo, Young Bin; Choi, Jeongim; Bae, Sang-Cheol; Boackle, Susan A.; Graham, Deborah Cunninghame; Vyse, Timothy J.; Guthridge, Joel M.; Gaffney, Patrick M.; Langefeld, Carl D.; Kelly, Jennifer A.; Greis, Kenneth D.; Kaufman, Kenneth M.; Harley, John B.; Kottyan, Leah C.

2015-01-01

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1. PMID:25865496

Actigraphy Measured Sleep Indices and Adiposity: The Multi-Ethnic Study of Atherosclerosis (MESA)

PubMed Central

Ogilvie, Rachel P.; Redline, Susan; Bertoni, Alain G.; Chen, Xiaoli; Ouyang, Pamela; Szklo, Moyses; Lutsey, Pamela L.

2016-01-01

Study Objectives: To investigate the cross-sectional relationship between objectively measured sleep characteristics and multiple indices of adiposity in racially/ethnically diverse older adults within the MESA Sleep study (n = 2,146). Methods: 7-day actigraphy was used to assess sleep duration, sleep efficiency, and night-to-night variability. Body mass index (BMI), waist circumference, and total body fat were modeled continuously and according to obesity cut-points. Models were adjusted for demographic, socioeconomic, and behavioral variables. Results: Participants who slept less than 6 hours a night had significantly higher BMI, waist circumference, and body fat relative to those who slept 7–8 hours. Those who slept less than 5 hours had a 16% higher prevalence of general obesity (BMI ≥ 30 vs. < 25 kg/m2) (95% [CI]: 0.08–0.24) and a 9% higher prevalence of abdominal obesity (waist circumference: women ≥ 88 centimeters, men ≥ 102 centimeters; 95% CI: 0.03–0.16) compared to those who slept 7–8 hours. Results were similar for sleep efficiency and night-to-night sleep variability. Conclusions: Among an older multi-ethnic cohort, we found robust associations across multiple indices of sleep and adiposity. Targeting sleep characteristics may be of benefit in obesity interventions, but more research is needed to rule out reverse causality. Citation: Ogilvie RP, Redline S, Bertoni AG, Chen X, Ouyang P, Szklo M, Lutsey PL. Actigraphy measured sleep indices and adiposity: the Multi-Ethnic Study of Atherosclerosis (MESA). SLEEP 2016;39(9):1701–1708. PMID:27306270

I Am Newly Diagnosed with Lupus

MedlinePlus

... therapies can help control joint and muscle pain. article Learning to accept your lupus Learning to live with lupus involves making some changes -- physical, emotional, and spiritual. blog ... article Strategies for managing fatigue The common causes of ...

Treatment of severe lupus nephritis: the new horizon.

PubMed

Chan, Tak Mao

2015-01-01

Lupus nephritis is a common and severe manifestation of systemic lupus erythematosus, and an important cause of both acute kidney injury and end-stage renal disease. Despite its aggressive course, lupus nephritis is amenable to treatment in the majority of patients. The paradigm of immunosuppressive treatment for lupus nephritis has evolved over the past few decades from corticosteroids alone to corticosteroids combined with cyclophosphamide. Sequential treatment regimens using various agents have been formulated for induction and long-term maintenance therapy, and mycophenolate mofetil has emerged as a standard of care option for both induction and maintenance immunosuppressive treatment. The current era has witnessed the emergence of multiple novel therapeutic options, such as calcineurin inhibitors and biologic agents that target key pathogenetic mechanisms of lupus nephritis. Clinical outcomes have improved in parallel with these therapeutic advances. This Review discusses the evidence in support of current standard of care immunosuppressive treatments and emerging therapies, and describes their roles and relative merits in the management of patients with lupus nephritis.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus.

PubMed

Kwon, H H; Bang, S Y; Won, S; Park, Y; Yi, J H; Joo, Y B; Lee, H S; Bae, S C

2018-01-01

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were

Immunometabolism in systemic lupus erythematosus.

PubMed

Morel, Laurence

2017-05-01

Systemic lupus erythematosus (SLE) is an autoimmune disease mediated by pathogenic autoantibodies directed against nucleoprotein complexes. Beyond the activation of autoreactive B cells, this process involves dysregulation in many other types of immune cells, including CD4 + T cells, dendritic cells, macrophages and neutrophils. Metabolic substrate utilization and integration of cues from energy sensors are critical checkpoints of effector functions in the immune system, with common as well as cell-specific programmes. Patients with SLE and lupus-prone mice present with activated metabolism of CD4 + T cells, and the use of metabolic inhibitors to normalize these features is associated with therapeutic effects. Far less is known about the metabolic requirements of B cells and myeloid cells in SLE. This article reviews current knowledge of the alterations in metabolism of immune cells in patients with SLE and mouse models of lupus in the context of what is known about the metabolic regulation of these cells during normal immune responses. How these alterations might contribute to lupus pathogenesis and how they can be targeted therapeutically are also discussed.

Clozapine-induced systemic lupus erythematosus.

PubMed

Rami, Abu Fanne; Barkan, Daniel; Mevorach, Dror; Leitersdorf, Eran; Caraco, Yoseph

2006-05-01

To report a case of classic clozapine-induced systemic lupus erythematosus that also developed on rechallenge. A 32-year-old white woman diagnosed with schizophrenia presented in 1996 with clinical characteristics and laboratory markers consistent with drug-induced lupus (DIL). Clozapine, started 1 year prior, was withdrawn, with complete biological and clinical remission within 3 months. In 2004, 1 week after rechallenge with clozapine for uncontrolled schizophrenia, the patient developed clinical and biological signs and symptoms consistent with the diagnosis of DIL. Again, discontinuation of clozapine was followed by full remission within 2-3 months. DIL was first described more than 50 years ago, with multiple drugs implicated in the causation. Clozapine-induced lupus was reported recently, but does not meet the usual criteria for a diagnosis of DIL. We report a classic case of clozapine-induced lupus that, according to the Naranjo probability scale, demonstrates a highly probable relationship between DIL and clozapine. DIL demands a high index of suspicion for diagnosis. Although clozapine has an extensive safety profile, DIL must be considered as one of its serious adverse effects.

Malignancy in Pediatric-onset Systemic Lupus Erythematosus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Zahedi Niaki, Omid; Labrecque, Jeremy; Schanberg, Laura E; Silverman, Earl D; Hayward, Kristen; Imundo, Lisa; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; Oen, Kiem; Wagner-Weiner, Linda; Rosenberg, Alan M; O'Neil, Kathleen M; Duffy, Ciarán M; von Scheven, Emily; Joseph, Lawrence; Lee, Jennifer L; Ramsey-Goldman, Rosalind

2017-10-01

To determine cancer incidence in a large pediatric-onset systemic lupus erythematosus (SLE) population. Data were examined from 12 pediatric SLE registries in North America. Patients were linked to their regional cancer registries to detect cancers observed after cohort entry, defined as date first seen in the clinic. The expected number of malignancies was obtained by multiplying the person-years in the cohort (defined from cohort entry to end of followup) by the geographically matched age-, sex-, and calendar year-specific cancer rates. The standardized incidence ratio (SIR; ratio of cancers observed to expected) was generated, with 95% CI. A total of 1168 patients were identified from the registries. The mean age at cohort entry was 13 years (SD 3.3), and 83.7% of the subjects were female. The mean duration of followup was 7.6 years, resulting in a total observation period of 8839 years spanning the calendar period 1974-2009. During followup, fourteen invasive cancers occurred (1.6 cancers per 1000 person-yrs, SIR 4.13, 95% CI 2.26-6.93). Three of these were hematologic (all lymphomas), resulting in an SIR for hematologic cancers of 4.68 (95% CI 0.96-13.67). SIR were increased for both male and female patients, and across age groups. Although cancer remains a relatively rare outcome in pediatric-onset SLE, our data do suggest an increase in cancer for patients followed an average of 7.6 years. About one-fifth of the cancers were hematologic. Longer followup, and study of drug effects and disease activity, is warranted.

Genome-Wide Association Study in African-Americans with Systemic Lupus Erythematosus

DTIC Science & Technology

2013-09-01

Americans with Systemic Lupus Erythematosus PRINCIPAL INVESTIGATOR: John Harley, M.D., Ph.D...SUPPLEMENTARY NOTES 14. ABSTRACT Systemic lupus erythematosus ( lupus ) is a potentially deadly systemic autoimmune disease that disproportionately... Systemic lupus erythematosus ( lupus ) is a potentially deadly systemic autoimmune disease that disproportionately afflicts women and African

The needs of persons with lupus and health care providers: a qualitative study aimed toward the development of the Lupus Interactive Navigator™.

PubMed

Neville, C; Da Costa, D; Mill, C; Rochon, M; Aviña-Zubieta, J A; Pineau, C A; Eng, D; Fortin, P R

2014-02-01

Systemic lupus erythematosus is an inflammatory autoimmune disease associated with high morbidity and unacceptable mortality. A major challenge for persons with lupus is coping with their illness and complex care. Our objective was to identify the informational and resource needs of persons with lupus, rheumatologists, and allied health professionals treating lupus. Our findings will be applied toward the development of an innovative web-based technology, the Lupus Interactive Navigator (LIN™), to facilitate and support engagement and self-management for persons with lupus. Eight focus groups were conducted: four groups of persons with lupus (n=29), three groups of rheumatologists (n=20), and one group of allied health professionals (n=8). The groups were held in British Columbia, Ontario, and Quebec. All sessions were audio-recorded and transcribed verbatim. Qualitative analysis was performed using grounded theory. The transcripts were reviewed independently and coded by the moderator and co-moderator using 1) qualitative data analysis software developed by Provalis Research, Montreal, Canada, and 2) manual coding. Four main themes emerged: 1) specific information and resource needs; 2) barriers to engagement in health care; 3) facilitators of engagement in health care; and 4) tools identified as helpful for the self-management of lupus. These findings will help guide the scope of LIN™ with relevant information topics and specific tools that will be most helpful to the diverse needs of persons with lupus and their health care providers.

Dietary Choline and Betaine Intakes Vary in an Adult Multiethnic Population123

PubMed Central

Yonemori, Kim M.; Lim, Unhee; Koga, Karin R.; Wilkens, Lynne R.; Au, Donna; Boushey, Carol J.; Le Marchand, Loïc; Kolonel, Laurence N.; Murphy, Suzanne P.

2013-01-01

Choline and betaine are important nutrients for human health, but reference food composition databases for these nutrients became available only recently. We tested the feasibility of using these databases to estimate dietary choline and betaine intakes among ethnically diverse adults who participated in the Multiethnic Cohort (MEC) Study. Of the food items (n = 965) used to quantify intakes for the MEC FFQ, 189 items were exactly matched with items in the USDA Database for the Choline Content of Common Foods for total choline, choline-containing compounds, and betaine, and 547 items were matched to the USDA National Nutrient Database for Standard Reference for total choline (n = 547) and 148 for betaine. When a match was not found, choline and betaine values were imputed based on the same food with a different form (124 food items for choline, 300 for choline compounds, 236 for betaine), a similar food (n = 98, 284, and 227, respectively) or the closest item in the same food category (n = 6, 191, and 157, respectively), or the values were assumed to be zero (n = 1, 1, and 8, respectively). The resulting mean intake estimates for choline and betaine among 188,147 MEC participants (aged 45–75) varied by sex (372 and 154 mg/d in men, 304 and 128 mg/d in women, respectively; P-heterogeneity < 0.0001) and by race/ethnicity among Caucasians, African Americans, Japanese Americans, Latinos, and Native Hawaiians (P-heterogeneity < 0.0001), largely due to the variation in energy intake. Our findings demonstrate the feasibility of assessing choline and betaine intake and characterize the variation in intake that exists in a multiethnic population. PMID:23616508

Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens

PubMed Central

Lech, Maciej; Kulkarni, Onkar P.; Pfeiffer, Stephanie; Savarese, Emina; Krug, Anne; Garlanda, Cecilia; Mantovani, Alberto; Anders, Hans-Joachim

2008-01-01

The Sigirr gene (also known as Tir8) encodes for an orphan receptor of the Toll-like receptor (TLR)/interleukin 1 receptor family that inhibits TLR-mediated pathogen recognition in dendritic cells. Here, we show that Sigirr also inhibits the activation of dendritic cells and B cells upon exposure to RNA and DNA lupus autoantigens. To evaluate the functional role of Sigirr in the pathogenesis of systemic lupus erythematosus (SLE), we generated Sigirr-deficient C57BL/6-lpr/lpr mice. These mice developed a progressive lymphoproliferative syndrome followed by severe autoimmune lung disease and lupus nephritis within 6 mo of age as compared with the minor abnormalities observed in C57BL/6-lpr/lpr mice. Lack of Sigirr was associated with enhanced activation of dendritic cells and increased expression of multiple proinflammatory and antiapoptotic mediators. In the absence of Sigirr, CD4 T cell numbers were increased and CD4+CD25+ T cell numbers were reduced. Furthermore, lack of Sigirr enhanced the activation and proliferation of B cells, including the production of autoantibodies against multiple nuclear lupus autoantigens. These data identify Sigirr as a novel SLE susceptibility gene in mice. PMID:18644972

Multicultural and Multiethnic Education in Japan

ERIC Educational Resources Information Center

Nomoto, Hiroyuki

2009-01-01

In Japan, the Ainu people have been living mainly in Hokkaido and many Koreans continue to live since the end of the World War Two. Since 1990's, the number of migrant workers has increased rapidly. In this sense, Japanese society has been multicultural and multiethnic. However, those minority groups have been strictly discriminated against in…

Immune Cell Metabolism in Systemic Lupus Erythematosus.

PubMed

Choi, Seung-Chul; Titov, Anton A; Sivakumar, Ramya; Li, Wei; Morel, Laurence

2016-11-01

Cellular metabolism represents a newly identified checkpoint of effector functions in the immune system. A solid body of work has characterized the metabolic requirements of normal T cells during activation and differentiation into polarized effector subsets. Similar studies have been initiated to characterize the metabolic requirements for B cells and myeloid cells. Only a few studies though have characterized the metabolism of immune cells in the context of autoimmune diseases. Here, we review what is known on the altered metabolic patterns of CD4 + T cells, B cells, and myeloid cells in lupus patients and lupus-prone mice and how they contribute to lupus pathogenesis. We also discuss how defects in immune metabolism in lupus can be targeted therapeutically.

Current and Emerging Therapies for Lupus Nephritis

PubMed Central

Parikh, Samir V.

2016-01-01

The introduction of corticosteroids and later, cyclophosphamide dramatically improved survival in patients with proliferative lupus nephritis, and combined administration of these agents became the standard-of-care treatment for this disease. However, treatment failures were still common and the rate of progression to ESRD remained unacceptably high. Additionally, treatment was associated with significant morbidity. Therefore, as patient survival improved, the goals for advancing lupus nephritis treatment shifted to identifying therapies that could improve long-term renal outcomes and minimize treatment-related toxicity. Unfortunately, progress has been slow and the current approaches to the management of lupus nephritis continue to rely on high-dose corticosteroids plus a broad-spectrum immunosuppressive agent. Over the past decade, an improved understanding of lupus nephritis pathogenesis fueled several clinical trials of novel drugs, but none have been found to be superior to the combination of a cytotoxic agent and corticosteroids. Despite these trial failures, efforts to translate mechanistic advances into new treatment approaches continue. In this review, we discuss current therapeutic strategies for lupus nephritis, briefly review recent advances in understanding the pathogenesis of this disease, and describe emerging approaches developed on the basis of these advances that promise to improve upon the standard-of-care lupus nephritis treatments. PMID:27283496

Minneapolis Multi-Ethnic Curriculum Development Teacher's Guide.

ERIC Educational Resources Information Center

Tipple, Bruce E.; Whitehead, Pamela

The teacher's guide describes learning activities and teaching methods for the Minneapolis Multi-Ethnic Curriculum Project for secondary schools. It is divided into eight sections. Section I lists knowledge generalizations and important concepts for each section. The remaining seven sections are entitled ethnicity, migration, acculturation, ethnic…

Minneapolis Multi-Ethnic Curriculum Project. Unit Overviews.

ERIC Educational Resources Information Center

Skjervold, Christian K.; Tipple, Bruce

The document presents unit overviews describing activities in the Minneapolis Multi-Ethnic Curriculum Project for secondary schools. It is divided into seven sections, each relating to a specific topic. Sections are entitled ethnicity, migration, acculturation, ethnic enclaves, family, prejudice/discrimination, and power. Each section offers from…

Impact of hydroxychloroquine on preterm delivery and intrauterine growth restriction in pregnant women with systemic lupus erythematosus: a descriptive cohort study.

PubMed

Leroux, M; Desveaux, C; Parcevaux, M; Julliac, B; Gouyon, J B; Dallay, D; Pellegrin, J L; Boukerrou, M; Blanco, P; Lazaro, E

2015-11-01

The aim of this study was to evaluate the effect of hydroxychloroquine (HCQ) on fetal preterm delivery and intrauterine growth restriction (IUGR) in a cohort of pregnant women with systemic lupus erythematosus (SLE). Over an 11-year period (January 1, 2001 to December 31, 2011), all women with SLE and admitted to deliver after 22 weeks of gestation to Bordeaux University Hospital (France), were retrospectively enrolled in the present study. The population was then split into two groups based on the treatment they received: HCQ exposed (HCQ+) versus HCQ non-exposed (HCQ-) group. 118 pregnancies were included, 41 in the HCQ+ group and 77 in the HCQ- group. The rate of adverse fetal outcome was significantly lower in the HCQ+ group (p = 0.001), particularly in terms of preterm delivery, 15.8% versus 44.2% (p = 0.006), and IUGR, 10.5% versus 28.6% (p = 0.03). No adverse outcomes were reported in the HCQ+ group. HCQ reduces neonatal morbidity in women with SLE by significantly decreasing the rate of prematurity and intrauterine growth restriction. © The Author(s) 2015.

Parenting, Family Processes, Relationships, and Parental Support in Multiracial and Multiethnic Families: An Exploratory Study of Youth Perceptions

ERIC Educational Resources Information Center

Lorenzo-Blanco, Elma I.; Bares, Cristina B.; Delva, Jorge

2013-01-01

Mixed-race or multiethnic youth are at risk for mental and physical health problems. We used data from the National Longitudinal Study of Youth 1997 to compare family characteristics of adolescents of a mixed-race or multiethnic background with those of a monoracial or monoethnic background. Mixed-race or multiethnic youth reported feeling less…

Lupus erythematosus: considerations about clinical, cutaneous and therapeutic aspects*

PubMed Central

Moura Filho, Jucélio Pereira; Peixoto, Raiza Luna; Martins, Lívia Gomes; de Melo, Sillas Duarte; de Carvalho, Ligiana Leite; Pereira, Ana Karine F. da Trindade C.; Freire, Eutilia Andrade Medeiros

2014-01-01

Systemic Lupus Erythematosus is a chronic inflammatory disease with multifactorial etiology. Although clinical manifestations are varied, the skin is an important target-organ, which contributes to the inclusion of skin lesions in 4 out of the 17 new criteria for the diagnosis of the disease, according to the Systemic Lupus International Collaborating Clinics. The cutaneous manifestations of lupus are pleomorphic. Depending on their clinical characteristics, they can be classified into Acute Cutaneous Lupus Erythematosus, Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus and Intermittent Cutaneous Lupus Erythematosus. Treatment is based on preventive measures, reversal of inflammation, prevention of damage to target organs and relief of adverse events due to pharmacological therapy. The most commonly used treatment options are topical, systemic and surgical treatment, as well as phototherapy. The correct handling of the cases depends on a careful evaluation of the morphology of the lesions and the patient's general status, always taking into consideration not only the benefits but also the side effects of each therapeutic proposal. PMID:24626656

Antibodies against C1q Are a Valuable Serological Marker for Identification of Systemic Lupus Erythematosus Patients with Active Lupus Nephritis

PubMed Central

Chi, Shuhong; Yu, Yunxia; Shi, Juan; Zhang, Yurong; Yang, Jijuan; Yang, Lijuan; Liu, Xiaoming

2015-01-01

Objective. An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the diagnostic values of circulating autoantibodies to C1q alone or in combination with other markers for accessing active SLE and LN were evaluated. Methods. The diagnostic value of anti-C1q autoantibodies for identification of patients with active SLE disease and LN was evaluated by analyzing the level of anti-C1q antibodies in sera from 95 SLE patients, 40 non-SLE patients, and 34 healthy cohorts. Results. The prevalence of anti-C1q antibodies was significantly higher in patients with SLE (50/95, 52.6%), active SLE (40/51, 78.4%), and LN (30/35, 85.7%) in comparison with non-SLE patient controls, patients with inactive SLE, and non-LN, respectively. A combination of anti-C1q with anti-dsDNA and/or levels of complements C3 and C4 exhibited an increased specificity but a decreased sensitivity for identification of patients with active SLE and LN diseases relative to each of these markers alone. Conclusion. Anti-C1q antibodies were strongly associated with disease activity and LN in SLE patients, suggesting that it may be a reliable serological marker for identification of SLE patients with active LN and active SLE disease. PMID:26549923

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2013-12-01

RhoB. 15. SUBJECT TERMS RhoB, animal model, antibody secretion, antibody therapy, Systemic lupus erythematosus , autoantibodies. 16. SECURITY...9. Other Achievements 10. References 11. Appendices 1. INTRODUCTION: Systemic lupus erythematosus (SLE) affects approximately 300,000 to over...therapy, Systemic lupus erythematosus , autoantibodies. 3. OVERALL PROJECT SUMMARY: Objective to complete in the award period of 18 months

Minneapolis Multi-Ethnic Curriculum Project--Migration Unit.

ERIC Educational Resources Information Center

Minneapolis Public Schools, Minn. Dept. of Intergroup Education.

The student booklet presents short chapters illustrating the migration unit of the Minneapolis Multi-Ethnic Curriculum Project for secondary schools. Sixteen brief chapters describe migration, immigration, and emigration in the United States. The first six chapters offer first person accounts of immigrants from Norway, Korea, Egypt, Hitler's…

Minneapolis Multi-Ethnic Curriculum Project--Acculturation Unit.

ERIC Educational Resources Information Center

Skjervold, Christian K.; And Others

The student booklet presents short case studies illustrating the acculturation unit of the Minneapolis Multi-Ethnic Curriculum Project for secondary schools. It is presented in nine chapters. Chapter I provides background information on immigration and points out ways acculturation takes place. Chapter II, "Barrio Boy," tells of life in…

The treatment of systemic lupus proliferative nephritis.

PubMed

Punaro, Marilynn G

2013-11-01

Lupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE) in childhood affecting more than 80% of patients. Treatment of this complication has undergone significant evolution in recent years. A series of randomized controlled trials has clarified the role of a variety of immunomodulating regimens including some novel biologic medications. This review touches on the major trials that have influenced practice and shaped current thinking about the treatment of proliferative lupus glomerulonephritis.

Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary

PubMed Central

Pons-Estel, Guillermo J.; Molineros, Julio; Wojdyla, Daniel; McGwin, Gerald; Nath, Swapan K.; Pons-Estel, Bernardo A.; Alarcón-Riquelme, Marta; Alarcón, Graciela S.

2016-01-01

Objective. To evaluate disease features and outcomes in two populations with significant Amerindian ancestry. Methods. Hispanic patients (from Texas) from the Lupus in Minorities: Nature versus Nurture (LUMINA) cohort and Mestizo patients from the Grupo Latino Americano De Estudio del Lupus or Latin American Group for the Study of Lupus (GLADEL) cohort were included. Disease features and outcomes were evaluated at baseline and last visit. Admixture informative markers of Mestizo Genoma de Lupus Eritematoso Sistémico Network consortium (GENLES) patients and Hispanic LUMINA patients were compared. Univariable analyses were performed using Chi square or Student’s t test as appropriate. Multivariable analyses adjusting for possible confounders were carried out using Poisson, logistic or Cox regression models as appropriate. Results. A total of 114 LUMINA and 619 GLADEL patients were included. GLADEL patients had accrued more damage at baseline, but the opposite was the case at last visit. Being from LUMINA was a risk factor for damage accrual, even after adjusting for possible confounders [relative risk (RR) 1.33, 95% CI 1.12, 1.58]. Also, LUMINA patients have a higher risk of mortality than GLADEL patients [hazard ratio (HR) 2.37, 95% CI 1.10, 5.15], having 5-year survival of 85.6% and 94.5%, respectively. In addition, 79 LUMINA patients and 744 Mestizo GENLES patients were evaluated in order to compare genetic ancestry between the two groups; GENLES patients had a higher proportion of European ancestry (48.5% vs 43.3%, P = 0.003) and a lower proportion of Asian ancestry (3.7% vs 4.9%, P = 0.048), but the proportions of Amerindian and African ancestry were comparable in both. Conclusion. USA Hispanic patients seemed to have a poorer prognosis than their counterparts from Latin America, despite having a comparable genetic background. Socioeconomic factors may account for these observations. PMID:26412809

Rituximab in systemic lupus erythematosus and lupus nephritis.

PubMed

Beckwith, Hannah; Lightstone, Liz

2014-01-01

Treatment options for systemic lupus erythematosus (SLE) and lupus nephritis (LN) have high associated morbidity and mortality. Side effects, particularly from long-term corticosteroid usage, limit patient adherence, with subsequent impacts on treatment efficacy. In addition, a subset of patients with SLE/LN fails to respond to current standard immunotherapy. There is an urgent need to develop steroid-sparing treatment regimens as well as novel therapies for the management of refractory disease. Rituximab is a chimeric mouse/human monoclonal antibody directed against the B cell CD20 receptor. It has been used in the treatment of non-Hodgkin's lymphoma for over 30 years and has an excellent safety profile. Recent work has demonstrated a role for B cell depletion therapy in the management of autoimmune disease, and the efficacy of rituximab in many observational studies in SLE and LN has been noted. Unfortunately, two large randomised controlled trials evaluating rituximab for the treatment of renal and non-renal lupus failed to meet their primary endpoints. Reasons for this have been discussed extensively within the medical community with a general consensus that trial design (steroid use, trial size and endpoints used) was the principal reason for the failures. Despite the lack of trial evidence, clinical experience means many physicians firmly believe in the value of rituximab in SLE/LN treatment and have continued to use it in their clinical practice. Recent work has demonstrated the efficacy of rituximab as a steroid-sparing agent and as an alternative therapeutic option for refractory SLE/LN. There are two further rituximab randomised controlled trials planned/started in LN – one using a steroid-minimising regimen with rituximab for induction and one evaluating rituximab for LN refractory to 6 months standard of care treatment. Rituximab remains a problematic drug in lupus and LN – it is a biologically plausible agent with a huge amount of supportive

Fruit and Vegetable Intakes Are Associated with Lower Risk of Bladder Cancer among Women in the Multiethnic Cohort Study12

PubMed Central

Park, Song-Yi; Ollberding, Nicholas J.; Woolcott, Christy G.; Wilkens, Lynne R.; Henderson, Brian E.; Kolonel, Laurence N.

2013-01-01

Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients, phytochemicals, and antioxidants with potentially anticarcinogenic properties. In a prospective analysis of 185,885 older adults participating in the Multiethnic Cohort Study, we examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk. Cox proportional hazards models were used to calculate HRs and 95% CIs for bladder cancer in relation to dietary intakes. A total of 581 invasive bladder cancer cases (429 men and 152 women) were diagnosed over a mean follow-up period of 12.5 y. In women, total fruits and vegetables [HR = 0.35 (95% CI: 0.22, 0.56); highest vs. lowest quartile], total vegetables [HR = 0.49 (95% CI: 0.29, 0.83)], yellow-orange vegetables [HR = 0.48 (95% CI: 0.30, 0.77)], total fruits [HR = 0.54 (95% CI: 0.34, 0.85)], and citrus fruits [HR = 0.56 (95% CI: 0.34, 0.90)] were inversely associated with the risk of invasive bladder cancer in risk factor-adjusted models. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids α-carotene, β-carotene, and β-cryptoxanthin; and folate had a lower risk of bladder cancer. For men, no associations for fruits, vegetables, or nutrients were found overall, although inverse associations were observed for vegetable intake among current smokers, and in ethnic-specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of invasive bladder cancer among women and highlight the need for specific subgroup analyses in future studies. PMID:23739308

A priori-defined diet quality indices, biomarkers and risk for type 2 diabetes in five ethnic groups: the Multiethnic Cohort.

PubMed

Jacobs, Simone; Boushey, Carol J; Franke, Adrian A; Shvetsov, Yurii B; Monroe, Kristine R; Haiman, Christopher A; Kolonel, Laurence N; Le Marchand, Loic; Maskarinec, Gertraud

2017-08-01

Dietary indices have been related to risk for type 2 diabetes (T2D) predominantly in white populations. The present study evaluated this association in the ethnically diverse Multiethnic Cohort and examined four diet quality indices in relation to T2D risk, homoeostatic model assessment-estimated insulin resistance (HOMA-IR) and biomarkers of dyslipidaemia, inflammation and adipokines. The T2D analysis included 166 550 white, African American, Native Hawaiian, Japanese American and Latino participants (9200 incident T2D cases). Dietary intake was assessed at baseline using a quantitative FFQ and T2D status was based on three self-reports and confirmed by administrative data. Biomarkers were assessed about 10 years later in a biomarker subcohort (n 10 060). Sex- and ethnicity-specific hazard ratios were calculated for the Healthy Eating Index-2010 (HEI-2010), the alternative HEI-2010 (AHEI-2010), the alternate Mediterranean diet score (aMED) and the Dietary Approaches to Stop Hypertension (DASH). Multivariable-adjusted means of biomarkers were compared across dietary index tertiles in the biomarker subcohort. The AHEI-2010, aMED (in men only) and DASH scores were related to a 10-20 % lower T2D risk, with the strongest associations in whites and the direction of the relationships mostly consistent across ethnic groups. Higher scores on the four indices were related to lower HOMA-IR, TAG and C-reactive protein concentrations, not related to leptin, and the DASH score was directly associated with adiponectin. The AHEI-2010 and DASH were directly related to HDL-cholesterol in women. Potential underlying biological mechanisms linking diet quality and T2D risk are an improved lipid profile and reduced systemic inflammation and, with regards to DASH alone, an improved adiponectin profile.

Hair and Scalp Changes in Cutaneous and Systemic Lupus Erythematosus.

PubMed

Udompanich, Siriorn; Chanprapaph, Kumutnart; Suchonwanit, Poonkiat

2018-06-09

Cutaneous and systemic lupus erythematosus (SLE) commonly involves the hair and scalp. Alopecia can result from direct activity of disease on the scalp or from the state of physical stress in the form of telogen effluvium. Discoid lupus erythematosus and lupus panniculitis/profundus are known to cause scarring alopecia, while accumulation of recent studies has shown that non-scarring alopecia in SLE may have different subtypes, comprising lupus erythematosus-specific and lupus erythematosus-nonspecific changes on histology. This review aims to summarize the clinical pattern, trichoscopic, histopathological, and direct immunofluorescence features of different types of alopecia in cutaneous and systemic lupus erythematosus, as well as exploring their relationship with SLE disease activity.

The Non-Muscle Myosin Heavy Chain 9 Gene (MYH9) Is Not Associated with Lupus Nephritis in African Americans

PubMed Central

Freedman, Barry I.; Edberg, Jeffrey C.; Comeau, Mary E.; Murea, Mariana; Bowden, Donald W.; Divers, Jasmin; Alarcón, Graciela S.; Brown, Elizabeth E.; McGwin, Gerald; Kopp, Jeffrey B.; Winkler, Cheryl A.; Nelson, George W.; Illei, Gabor; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Vilá, Luis M.; Langefeld, Carl D.; Kimberly, Robert P.

2010-01-01

Background African Americans (AA) disproportionately develop lupus nephritis (LN) relative to European Americans and familial clustering supports causative genes. Since MYH9 underlies approximately 40% of end-stage renal disease (ESRD) in AA, we tested for genetic association with LN. Methods Seven MYH9 single nucleotide polymorphisms (SNPs) and the E1 risk haplotype were tested for association with LN in three cohorts of AA. Results A preliminary analysis revealed that the MYH9 E1 risk haplotype was associated with ESRD in 25 cases with presumed systemic lupus erythematosus (SLE)-associated ESRD, compared to 735 non-SLE controls (odds ratio 3.1; p = 0.010 recessive). Replication analyses were performed in 583 AA with SLE in the PROFILE cohort (318 with LN; 265 with SLE but without nephropathy) and 60 AA from the NIH (39 with LN; 21 with SLE but without nephropathy). Analysis of the NIH and larger PROFILE cohorts, as well as a combined analysis, did not support this association. Conclusions These results suggest that AA with ESRD and coincident SLE who were recruited from dialysis clinics more likely have kidney diseases in the MYH9-associated spectrum of focal segmental glomerulosclerosis. PROFILE and NIH participants, recruited from rheumatology practices, demonstrate that MYH9 does not contribute substantially to the development of LN in AA. PMID:20523037

Serum calcification propensity is independently associated with disease activity in systemic lupus erythematosus

PubMed Central

Chalikias, George; Tziakas, Dimitrios; Chizzolini, Carlo; Ribi, Camillo; Trendelenburg, Marten; Eisenberger, Ute; Hauser, Thomas; Pasch, Andreas; Huynh-Do, Uyen; Arampatzis, Spyridon

2018-01-01

Background Systemic lupus erythematosus (SLE) is associated with severe cardiovascular complications. The T50 score is a novel functional blood test quantifying calcification propensity in serum. High calcification propensity (or low T50) is a strong and independent determinant of all-cause mortality in various patient populations. Methods A total of 168 patients with ≥ 4 American College of Rheumatology (ACR) diagnostic criteria from the Swiss Systemic lupus erythematosus Cohort Study (SSCS) were included in this analysis. Serum calcification propensity was assessed using time-resolved nephelometry. Results The cohort mainly consisted of female (85%), middle-aged (43±14 years) Caucasians (77%). The major determinants of T50 levels included hemoglobin, serum creatinine and serum protein levels explaining 43% of the variation at baseline. Integrating disease activity (SELENA-SLEDAI) into this multivariate model revealed a significant association between disease activity and T50 levels. In a subgroup analysis considering only patients with active disease (SELENA-SLEDAI score ≥4) we found a negative association between T50 and SELENA-SLEDAI score at baseline (Spearman’s rho -0.233, P = 0.02). Conclusions Disease activity and T50 are closely associated. Moreover, T50 levels identify a subgroup of SLE patients with ongoing systemic inflammation as mirrored by increased disease activity. T50 could be a promising biomarker reflecting SLE disease activity and might offer an earlier detection tool for high-risk patients. PMID:29364894

Locating Multiethnic Families in a Globalizing World

ERIC Educational Resources Information Center

Trask, Bahira Sherif

2013-01-01

To derive new insights into the growing number of multiethnic, immigrant, transnational families in the United States and abroad, we need to incorporate the concept of globalization into our analysis. As the world becomes increasingly interconnected, an ever-growing number of heterogeneous individuals are associating with each other and being…

ABIN1 dysfunction as a genetic basis for lupus nephritis.

PubMed

Caster, Dawn J; Korte, Erik A; Nanda, Sambit K; McLeish, Kenneth R; Oliver, Rebecca K; G'sell, Rachel T; Sheehan, Ryan M; Freeman, Darrell W; Coventry, Susan C; Kelly, Jennifer A; Guthridge, Joel M; James, Judith A; Sivils, Kathy L; Alarcon-Riquelme, Marta E; Scofield, R Hal; Adrianto, Indra; Gaffney, Patrick M; Stevens, Anne M; Freedman, Barry I; Langefeld, Carl D; Tsao, Betty P; Pons-Estel, Bernardo A; Jacob, Chaim O; Kamen, Diane L; Gilkeson, Gary S; Brown, Elizabeth E; Alarcon, Graciela S; Edberg, Jeffrey C; Kimberly, Robert P; Martin, Javier; Merrill, Joan T; Harley, John B; Kaufman, Kenneth M; Reveille, John D; Anaya, Juan-Manuel; Criswell, Lindsey A; Vila, Luis M; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A; Vyse, Timothy J; Niewold, Timothy B; Cohen, Philip; Powell, David W

2013-11-01

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity.

ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis

PubMed Central

Caster, Dawn J.; Korte, Erik A.; Nanda, Sambit K.; McLeish, Kenneth R.; Oliver, Rebecca K.; G'Sell, Rachel T.; Sheehan, Ryan M.; Freeman, Darrell W.; Coventry, Susan C.; Kelly, Jennifer A.; Guthridge, Joel M.; James, Judith A.; Sivils, Kathy L.; Alarcon-Riquelme, Marta E.; Scofield, R. Hal; Adrianto, Indra; Gaffney, Patrick M.; Stevens, Anne M.; Freedman, Barry I.; Langefeld, Carl D.; Tsao, Betty P.; Pons-Estel, Bernardo A.; Jacob, Chaim O.; Kamen, Diane L.; Gilkeson, Gary S.; Brown, Elizabeth E.; Alarcon, Graciela S.; Edberg, Jeffrey C.; Kimberly, Robert P.; Martin, Javier; Merrill, Joan T.; Harley, John B.; Kaufman, Kenneth M.; Reveille, John D.; Anaya, Juan-Manuel; Criswell, Lindsey A.; Vila, Luis M.; Petri, Michelle; Ramsey-Goldman, Rosalind; Bae, Sang-Cheol; Boackle, Susan A.; Vyse, Timothy J.; Niewold, Timothy B.; Cohen, Philip

2013-01-01

The genetic factors underlying the pathogenesis of lupus nephritis associated with systemic lupus erythematosus are largely unknown, although animal studies indicate that nuclear factor (NF)-κB is involved. We reported previously that a knockin mouse expressing an inactive form of ABIN1 (ABIN1[D485N]) develops lupus-like autoimmune disease and demonstrates enhanced activation of NF-κB and mitogen-activated protein kinases in immune cells after toll-like receptor stimulation. In the current study, we show that ABIN1[D485N] mice develop progressive GN similar to class III and IV lupus nephritis in humans. To investigate the clinical relevance of ABIN1 dysfunction, we genotyped five single-nucleotide polymorphisms in the gene encoding ABIN1, TNIP1, in samples from European-American, African American, Asian, Gullah, and Hispanic participants in the Large Lupus Association Study 2. Comparing cases of systemic lupus erythematosus with nephritis and cases of systemic lupus erythematosus without nephritis revealed strong associations with lupus nephritis at rs7708392 in European Americans and rs4958881 in African Americans. Comparing cases of systemic lupus erythematosus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans but not at rs4958881 in African Americans. Our data suggest that variants in the TNIP1 gene are associated with the risk for lupus nephritis and could be mechanistically involved in disease development via aberrant regulation of NF-κB and mitogen-activated protein kinase activity. PMID:23970121

The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus.

PubMed

Taraborelli, M; Lazzaroni, M G; Martinazzi, N; Fredi, M; Cavazzana, I; Franceschini, F; Tincani, A

2016-12-16

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

The incidence and prevalence of systemic lupus erythematosus in the UK, 1999-2012.

PubMed

Rees, Frances; Doherty, Michael; Grainge, Matthew; Davenport, Graham; Lanyon, Peter; Zhang, Weiya

2016-01-01

To estimate the incidence and prevalence of systemic lupus erythematosus (SLE) in the UK over the period 1999-2012. A retrospective cohort study using the Clinical Practice Research Datalink (CPRD). The incidence was calculated per 100 000 person-years and the prevalence was calculated per 100 000 people for the period 1999-2012 and stratified by year, age group, gender, region and ethnicity. Three definitions of SLE were explored: (1) systemic lupus, (2) a fully comprehensive definition of lupus including cutaneous only lupus and (3) requiring supporting evidence of SLE in the medical record. Using our primary definition of SLE, the incidence during the study period was 4.91/100 000 person-years (95% CI 4.73 to 5.09), with an annual 1.8% decline (p<0.001). In contrast, the prevalence increased from 64.99/100 000 in 1999 (95% CI 62.04 to 67.93) (0.065%) to 97.04/100 000 in 2012 (95% CI 94.18 to 99.90) (0.097%). SLE was six times more common in women. The peak age of incidence was 50-59 years. There was regional variation in both incidence and prevalence. People of Black Caribbean ethnicity had the highest incidence and prevalence. Alternative definitions of SLE increased (definition 2) or decreased (definition 3) estimates of incidence and prevalence, but similar trends were found. The incidence of SLE has been declining but the prevalence has been increasing in the UK in recent years. Age, gender, region and ethnicity are risk factors for SLE. This is the first study to report ethnic differences on the incidence and prevalence of SLE using the CPRD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Interferon regulatory factor 5 gene polymorphism in Egyptian children with systemic lupus erythematosus.

PubMed

Hammad, A; Mossad, Y M; Nasef, N; Eid, R

2017-07-01

Background Increased expression of interferon-inducible genes is implicated in the pathogenesis of systemic lupus erythematosus (SLE). Interferon regulatory factor 5 (IRF5) is one of the transcription factors regulating interferon and was proved to be implicated in the pathogenesis of SLE in different populations. Objectives The objective of this study was to investigate the correlation between polymorphisms of the IRF5 gene and SLE susceptibility in a cohort of Egyptian children and to investigate their association with clinico-pathological features, especially lupus nephritis. Subjects and methods Typing of interferon regulatory factor 5 rs10954213, rs2004640 and rs2280714 polymorphisms were done using polymerase chain reaction-restriction fragment length polymorphism for 100 children with SLE and 100 matched healthy controls. Results Children with SLE had more frequent T allele and TT genotype of rs2004640 ( P c  = 0.003 and 0.024, respectively) compared to controls. Patients with nephritis had more frequent T allele of rs2004640 compared to controls ( P c  = 0.003). However the allele and genotype frequencies of the three studied polymorphisms did not show any difference in patients with nephritis in comparison to those without nephritis. Haplotype GTA of rs10954213, rs2004640 and rs2280714, respectively, was more frequent in lupus patients in comparison to controls ( p = 0.01) while the haplotype GGG was more frequent in controls than lupus patients ( p = 0.011). Conclusion The rs2004640 T allele and TT genotype and GTA haplotype of rs rs10954213, rs2004640, and rs2280714, respectively, can be considered as risk factors for the development of SLE. The presence of the rs2004640 T allele increases the risk of nephritis development in Egyptian children with SLE.

Lupus, discoid on a child's face (image)

MedlinePlus

The round or disk shaped (discoid) rash of lupus produces red, raised patches with scales. The pores ( ... The majority (approximately 90%) of individuals with discoid lupus have only skin involvement as compared to more ...

Advances in Understanding Air Pollution and Cardiovascular Diseases: The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)

PubMed Central

Kaufman, Joel D.; Spalt, Elizabeth W.; Curl, Cynthia L.; Hajat, Anjum; Jones, Miranda R.; Kim, Sun-Young; Vedal, Sverre; Szpiro, Adam A.; Gassett, Amanda; Sheppard, Lianne; Daviglus, Martha L.; Adar, Sara D.

2016-01-01

The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air) leveraged the platform of the MESA cohort into a prospective longitudinal study of relationships between air pollution and cardiovascular health. MESA Air researchers developed fine-scale, state-of-the-art air pollution exposure models for the MESA Air communities, creating individual exposure estimates for each participant. These models combine cohort-specific exposure monitoring, existing monitoring systems, and an extensive database of geographic and meteorological information. Together with extensive phenotyping in MESA—and adding participants and health measurements to the cohort—MESA Air investigated environmental exposures on a wide range of outcomes. Advances by the MESA Air team included not only a new approach to exposure modeling but also biostatistical advances in addressing exposure measurement error and temporal confounding. The MESA Air study advanced our understanding of the impact of air pollutants on cardiovascular disease and provided a research platform for advances in environmental epidemiology. PMID:27741981

Pyomyositis in childhood-systemic lupus erythematosus.

PubMed

Blay, Gabriela; Ferriani, Mariana P L; Buscatti, Izabel M; França, Camila M P; Campos, Lucia M A; Silva, Clovis A

2016-01-01

Pyomyositis is a pyogenic infection of skeletal muscle that arises from hematogenous spread and usually presents with localized abscess. This muscle infection has been rarely reported in adult-onset systemic lupus erythematous and, to the best of our knowledge, has not been diagnosed in pediatric lupus population. Among our childhood-onset systemic lupus erythematous population, including 289 patients, one presented pyomyositis. This patient was diagnosed with childhood-onset systemic lupus erythematous at the age of 10 years-old. After six years, while being treated with prednisone, azathioprine and hydroxychloroquine, she was hospitalized due to a 30-day history of insidious pain in the left thigh and no apparent trauma or fever were reported. Her physical examination showed muscle tenderness and woody induration. Laboratory tests revealed anemia, increased acute phase reactants and normal muscle enzymes. Computer tomography of the left thigh showed collection on the middle third of the vastus intermedius, suggesting purulent stage of pyomyositis. Treatment with broad-spectrum antibiotic was initiated, leading to a complete clinical resolution. In conclusion, we described the first case of pyomyositis during childhood in pediatric lupus population. This report reinforces that the presence of localized muscle pain in immunocompromised patients, even without elevation of muscle enzymes, should raise the suspicion of pyomyositis. A prompt antibiotic therapy is strongly recommended. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Proliferative lupus nephritis in the absence of overt systemic lupus erythematosus: A historical study of 12 adult patients.

PubMed

Touzot, Maxime; Terrier, Cécile Saint-Pastou; Faguer, Stanislas; Masson, Ingrid; François, Hélène; Couzi, Lionel; Hummel, Aurélie; Quellard, Nathalie; Touchard, Guy; Jourde-Chiche, Noémie; Goujon, Jean-Michel; Daugas, Eric

2017-12-01

Severe lupus nephritis in the absence of systemic lupus erythematosus (SLE) is a rare condition with an unclear clinical presentation and outcome.We conducted a historical observational study of 12 adult (age >18 years) patients with biopsy-proven severe lupus nephritis or lupus-like nephritis without SLE immunological markers at diagnosis or during follow-up. Excluded were patients with chronic infections with HIV or hepatitis B or C; patients with a bacterial infectious disease; and patients with pure membranous nephropathy. Electron microscopy was retrospectively performed when the material was available. End points were the proportion of patients with a complete response (urine protein to creatinine ratio <0.5 g/day and a normal or near-normal eGFR), partial response (≥50% reduction in proteinuria to subnephrotic levels and a normal or near-normal eGFR), or nonresponse at 12 months or later after the initiation of the treatment.The study included 12 patients (66% female) with a median age of 36.5 years. At diagnosis, median creatinine and proteinuria levels were 1.21 mg/dL (range 0.5-11.6) and 7.5 g/day (1.4-26.7), respectively. Six patients had nephrotic syndrome and acute kidney injury. Renal biopsy examinations revealed class III or class IV A/C lupus nephritis in all cases. Electron microscopy was performed on samples from 5 patients. The results showed mesangial and subendothelial dense deposits consistent with LN in 4 cases, and a retrospective diagnosis of pseudo-amyloid fibrillary glomerulonephritis was made in 1 patient.Patients received immunosuppressive therapy consisting of induction therapy followed by maintenance therapy, similar to treatment for severe lupus nephritis. Remission was recorded in 10 patients at 12 months after the initiation of treatment. One patient reached end-stage renal disease. After a median follow-up of 24 months, 2 patients relapsed.Lupus nephritis in the absence of overt SLE is a nosological entity requiring

[Lupus erythematosus panniculitis presenting as palpebral edema and parotiditis].

PubMed

Pérez-Pastor, G; Valcuende, F; Tomás, G; Moreno, M

2007-10-01

Lupus erythematosus panniculitis or lupus erythematosus profundus is characterized by inflammation of the deep dermis and subcutaneous tissue. It can occur in isolation or associated with chronic systemic or discoid lupus erythematosus. It usually consists of nodules and hardened subcutaneous plaques on the forehead, cheeks, proximal extremities, and buttocks. Periorbital and parotid involvement are rare and can lead to misdiagnosis. We present the case of a patient with lupus erythematosus panniculitis who presented with palpebral edema and involvement of the periocular fat and parotid gland.

Lupus nephritis

MedlinePlus

... time, kidney failure can result. Symptoms Symptoms of lupus nephritis include: Blood in the urine Foamy appearance to urine Swelling (edema) of any area of the body High blood pressure Exams and Tests The health care provider will perform a physical ...

Perceived Discrimination and Incident Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Everson-Rose, Susan A; Lutsey, Pamela L; Roetker, Nicholas S; Lewis, Tené T; Kershaw, Kiarri N; Alonso, Alvaro; Diez Roux, Ana V

2015-08-01

Perceived discrimination is positively related to cardiovascular disease (CVD) risk factors; its relationship with incident CVD is unknown. Using data from the Multi-Ethnic Study of Atherosclerosis, a population-based multiethnic cohort study of 6,508 adults aged 45-84 years who were initially free of clinical CVD, we examined lifetime discrimination (experiences of unfair treatment in 6 life domains) and everyday discrimination (frequency of day-to-day occurrences of perceived unfair treatment) in relation to incident CVD. During a median 10.1 years of follow-up (2000-2011), 604 incident events occurred. Persons reporting lifetime discrimination in ≥2 domains (versus none) had increased CVD risk, after adjustment for race/ethnicity and sociodemographic factors, behaviors, and traditional CVD risk factors (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 1.09, 1.70) and after control for chronic stress and depressive symptoms (HR = 1.28, 95% CI: 1.01, 1.60). Reported discrimination in 1 domain was unrelated to CVD (HR = 1.05, 95% CI: 0.86, 1.30). There were no differences by race/ethnicity, age, or sex. In contrast, everyday discrimination interacted with sex (P = 0.03). Stratified models showed increased risk only among men (for each 1-standard deviation increase in score, adjusted HR = 1.14, 95% CI: 1.03, 1.27); controlling for chronic stress and depressive symptoms slightly reduced this association (HR = 1.11, 95% CI: 0.99, 1.25). This study suggests that perceived discrimination is adversely related to CVD risk in middle-aged and older adults. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Antinucleosome antibodies as a marker of active proliferative lupus nephritis.

PubMed

Bigler, Cornelia; Lopez-Trascasa, Margarita; Potlukova, Eliska; Moll, Solange; Danner, Doris; Schaller, Monica; Trendelenburg, Marten

2008-04-01

Antinucleosome autoantibodies were previously described to be a marker of active lupus nephritis. However, the true prevalence of antinucleosome antibodies at the time of active proliferative lupus nephritis has not been well established. Therefore, the aim of this study is to define the prevalence and diagnostic value of autoantibodies against nucleosomes as a marker for active proliferative lupus nephritis. Prospective multicenter diagnostic test study. 35 adult patients with systemic lupus erythematosus (SLE) at the time of the renal biopsy showing active class III or IV lupus nephritis compared with 59 control patients with SLE. Levels of antinucleosome antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Kidney biopsy findings of class III or IV lupus nephritis at the time of sampling in a study population versus clinically inactive or no nephritis in a control population. Increased concentrations of antinucleosome antibodies were found in 31 of 35 patients (89%) with active proliferative lupus nephritis compared with 47 of 59 control patients (80%) with SLE. No significant difference between the 2 groups with regard to number of positive patients (P = 0.2) or antibody concentrations (P = 0.2) could be found. The area under the receiver operating characteristic curve as a marker of the accuracy of the test in discriminating between proliferative lupus nephritis and inactive/no nephritis in patients with SLE was 0.581 (95% confidence interval, 0.47 to 0.70; P = 0.2). Increased concentrations of anti-dsDNA antibodies were found in 33 of 35 patients (94.3%) with active proliferative lupus nephritis compared with 49 of 58 control patients (84.5%) with SLE (P = 0.2). In patients with proliferative lupus nephritis, significantly higher titers of anti-dsDNA antibodies were detected compared with control patients with SLE (P < 0.001). The area under the receiver operating characteristic curve in discriminating between proliferative lupus nephritis and

Relation between C-reactive protein levels and body composition in a multiethnic sample of school children in Hawaii.

PubMed

Brown, Daniel E; Mautz, William J; Warrington, Miyako; Allen, Lenard; Tefft, Harold A T; Gotshalk, Lincoln; Katzmarzyk, Peter T

2010-01-01

Adipose cells secrete proinflammatory cytokines that stimulate hepatic production of C-reactive protein (CRP). CRP levels are associated with adiposity levels in adults, adolescents, and older children but not in young children (age 2-3). This study examined the relation between CRP, adiposity, and cardiovascular and metabolic variables including blood pressure, glucose, and blood lipids in two young cohorts of children, averaging approximately 5.5 and 8.5 years, respectively. Children (N = 125) from eight elementary schools in the multiethnic community of Hilo Hawaii were recruited to fill out questionnaires, undergo anthropometrics and air displacement plethysmography, have resting blood pressure measured, and provide a finger stick blood sample for analysis of CRP, glucose, and blood lipids. There were no significant differences between the cohorts in ethnic make up, household income, or parents' educational attainment. No significant relation was found between CRP and either adiposity or cardiovascular/metabolic variables in the younger cohort. However, significant correlations were found between CRP and adiposity measures and blood pressure in the older cohort. There was no marked difference in association of CRP with BMI versus waist circumference or waist-to-hip ratio. In neither cohort was CRP significantly related to glucose or blood lipids. Both amount of fat mass and time duration for possessing the adipose tissue may be important factors in determining the relation between CRP and both adiposity and blood pressure. (c) 2010 Wiley-Liss, Inc.

Clinical Perspectives on Lupus Genetics: Advances and Opportunities

PubMed Central

James, Judith A.

2014-01-01

Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

Ethnic differences in the epidemiology of cutaneous lupus erythematosus in New Zealand.

PubMed

Jarrett, P; Thornley, S; Scragg, R

2016-11-01

Background The prevalence and variation by ethnicity of cutaneous lupus in New Zealand is not known. Therefore, a cross-sectional study to determine the prevalence and variation by ethnicity of cutaneous lupus in the ethnically diverse community of South Auckland, New Zealand, was undertaken. Methods Multiple sources were examined to determine the prevalence of acute cutaneous lupus erythematosus, subacute cutaneous erythematosus and discoid lupus erythematosus. Ethnicities examined were European, Māori/Pacific and Indian/Asian. Capture-recapture was used to determine the overall population prevalence of cutaneous lupus. Results A total of 145 cases of cutaneous lupus were identified. There were 22 men and 123 women, with an average age (standard deviation), respectively, of 46.4 (±21.5) and 43.1 (±14.8) years. There were 53 cases of acute cutaneous lupus erythematosus, 19 cases of subacute cutaneous erythematosus and 66 cases of discoid lupus erythematosus. The age and sex adjusted relative risk (95% confidence interval; CI) of Māori/Pacific compared to the European population was 2.47 (95% CI 1.67-3.67) for all types of cutaneous lupus, 1.60 (95% CI 0.84-3.18) for acute cutaneous lupus erythematosus, 0.09 (95% CI 0.01-1.1) for subacute cutaneous erythematosus and 5.96 (95% CI 3.06-11.6) for discoid lupus erythematosus. The overall prevalence of cutaneous lupus was 30.1 (95% CI 25.5-35.4) per 100,000. However, capture-recapture estimated the unadjusted prevalence of cutaneous lupus to be 86.0 (95% CI 78.1-94.7) per 100,000. Conclusion Māori and Pacific people in Auckland, New Zealand, have a greater relative risk of all types of cutaneous lupus compared to the European population and a particularly high risk of discoid lupus erythematosus.

Utility of urinary transferrin and ceruloplasmin in patients with systemic lupus erythematosus for differentiating patients with lupus nephritis.

PubMed

Urrego, Tomás; Ortiz-Reyes, Blanca; Vanegas-García, Adriana L; Muñoz, Carlos H; González, Luis A; Vásquez, Gloria; Gómez-Puerta, José A

2018-03-09

Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin

Activated protein C attenuates systemic lupus erythematosus and lupus nephritis in MRL-Fas(lpr) mice.

PubMed

Lichtnekert, Julia; Rupanagudi, Khader Valli; Kulkarni, Onkar P; Darisipudi, Murthy Narayana; Allam, Ramanjaneyulu; Anders, Hans-Joachim

2011-09-15

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease leading to inflammatory tissue damage in multiple organs (e.g., lupus nephritis). Current treatments including steroids, antimalarials, and immunosuppressive drugs have significant side effects. Activated protein C is a natural protein with anticoagulant and immunomodulatory effects, and its recombinant version has been approved by the U.S. Food and Drug Administration to treat severe sepsis. Given the similarities between overshooting immune activation in sepsis and autoimmunity, we hypothesized that recombinant activated protein C would also suppress SLE and lupus nephritis. To test this concept, autoimmune female MRL-Fas(lpr) mice were injected with either vehicle or recombinant human activated protein C from week 14-18 of age. Activated protein C treatment significantly suppressed lupus nephritis as evidenced by decrease in activity index, glomerular IgG and complement C3 deposits, macrophage counts, as well as intrarenal IL-12 expression. Further, activated protein C attenuated cutaneous lupus and lung disease as compared with vehicle-treated MRL-Fas(lpr) mice. In addition, parameters of systemic autoimmunity, such as plasma cytokine levels of IL-12p40, IL-6, and CCL2/MCP-1, and numbers of B cells and plasma cells in spleen were suppressed by activated protein C. The latter was associated with lower total plasma IgM and IgG levels as well as lower titers of anti-dsDNA IgG and rheumatoid factor. Together, recombinant activated protein C suppresses the abnormal systemic immune activation in SLE of MRL-Fas(lpr) mice, which prevents subsequent kidney, lung, and skin disease. These results implicate that recombinant activated protein C might be useful for the treatment of human SLE.

Pediatric Lupus – Are There Differences in Presentation, Genetics, Response to Therapy, Damage Accrual Compared to Adult Lupus?

PubMed Central

Brunner, Hermine I

2010-01-01

Summary Some complement deficiencies predispose to SLE early in life. Currently, there are no known unique physiological or genetic pathways that can explain the variability in disease phenotypes, as is suggested by studies directly and indirectly comparing cohorts of children and adults with SLE. Children present with more acute illness and have more frequent renal, hematologic and central nervous system involvement at the time of diagnosis compared to adults with SLE. Almost all children require corticosteroids during the course of their disease, and many are treated with immunosuppressive drugs. Despite of a general lack of co-morbid conditions, mortality rates remain higher with pediatric SLE compared to aSLE. Children and adolescents accrue more damage as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, especially in the renal, ocular and musculoskeletal organ systems. Conversely, cardiovascular mortality is more prevalent in adults with SLE. PMID:20202591

The role of epigenetic variation in the pathogenesis of systemic lupus erythematosus

PubMed Central

2011-01-01

The focus of the present review is on the extent to which epigenetic alterations influence the development of systemic lupus erythematosus. Lupus is a systemic autoimmune disease characterized by the production of autoantibodies directed at nuclear self-antigens. A DNA methylation defect in CD4+ T cells has long been observed in idiopathic and drug-induced lupus. Recent studies utilizing high-throughput technologies have further characterized the nature of the DNA methylation defect in lupus CD4+ T cells. Emerging evidence in the literature is revealing an increasingly interconnected network of epigenetic dysregulation in lupus. Recent reports describe variable expression of a number of regulatory microRNAs in lupus CD4+ T cells, some of which govern the expression of DNA methyltransferase 1. While studies to date have revealed a significant role for epigenetic defects in the pathogenesis of lupus, the causal nature of epigenetic variation in lupus remains elusive. Future longitudinal epigenetic studies in lupus are therefore needed. PMID:22044622

Large-Scale CO Maps of the Lupus Molecular Cloud Complex

NASA Astrophysics Data System (ADS)

Tothill, N. F. H.; Löhr, A.; Parshley, S. C.; Stark, A. A.; Lane, A. P.; Harnett, J. I.; Wright, G. A.; Walker, C. K.; Bourke, T. L.; Myers, P. C.

2009-11-01

Fully sampled degree-scale maps of the 13CO 2-1 and CO 4-3 transitions toward three members of the Lupus Molecular Cloud Complex—Lupus I, III, and IV—trace the column density and temperature of the molecular gas. Comparison with IR extinction maps from the c2d project requires most of the gas to have a temperature of 8-10 K. Estimates of the cloud mass from 13CO emission are roughly consistent with most previous estimates, while the line widths are higher, around 2 km s-1. CO 4-3 emission is found throughout Lupus I, indicating widespread dense gas, and toward Lupus III and IV. Enhanced line widths at the NW end and along the edge of the B 228 ridge in Lupus I, and a coherent velocity gradient across the ridge, are consistent with interaction between the molecular cloud and an expanding H I shell from the Upper-Scorpius subgroup of the Sco-Cen OB Association. Lupus III is dominated by the effects of two HAe/Be stars, and shows no sign of external influence. Slightly warmer gas around the core of Lupus IV and a low line width suggest heating by the Upper-Centaurus-Lupus subgroup of Sco-Cen, without the effects of an H I shell.

Long-Term Survival and Death Causes of Systemic Lupus Erythematosus in China

PubMed Central

Wang, Ziqian; Wang, Yanhong; Zhu, Rongrong; Tian, Xinping; Xu, Dong; Wang, Qian; Wu, Chanyuan; Zhang, Shangzhu; Zhao, Jiuliang; Zhao, Yan; Li, Mengtao; Zeng, Xiaofeng

2015-01-01

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with an increased risk of death compared to general population. Although previous studies showed improvement in survival of SLE, the long-term prognosis has not been elaborated in China. This study aims to integrate the observational studies estimating current long-term survival of Chinese SLE patients and analyze the death-cause situation of SLE in China. The study is a systemic review of English and non-English articles using MEDLINE, EMBASE, CNKI, WANFANG, and SINOMED databases. Additional studies were found by consultation with clinical experts, browse of references in selected papers, and search of related textbooks. Our major search terms were SLE, follow-up, prognosis, survival, mortality, and China. We included cohort studies for survival analysis, and both cohort studies and case series for death-cause analysis in China. The extraction of the articles were done by 2 authors independently using predesigned charts, including characteristics of study, clinical data, analyzing data, and study quality indicators. All pooled analyses were conducted both for random-effects model and fixed-effects model. Funnel plots and Egger regression tests were applied to check potential publication bias. Heterogeneity was tested by sensitivity analysis. We identified 5 studies for survival analysis comprising 4469 Chinese patients with SLE (380 observed deaths). Thirty-six studies were suitable for death-cause analysis with 2179 observed deaths (derived from more than 20,000 Chinese patients with SLE). The overall pooled survival rates for SLE in China were 94% for 5-year survival rate and 89% for 10-year survival rate after disease onset from the year 1995 to 2013, which were similar with previous publications in Asia-Pacific area. The proportions of different causes of death showed infection (33.2%), renal involvement (18.7%), lupus encephalopathy (13.8%), and cardiovascular disease (11.5%) as the

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2014-09-01

AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

Response to Antimalarials in Cutaneous Lupus Erythematosus A Prospective Analysis

PubMed Central

Chang, Aileen Y.; Piette, Evan W.; Foering, Kristen P.; Tenhave, Thomas R.; Okawa, Joyce; Werth, Victoria P.

2012-01-01

Objective To demonstrate response to antimalarials in patients with cutaneous lupus erythematosus using activity scores from the Cutaneous Lupus Erythematosus Disease Area and Severity Index, a validated outcome measure. Design Prospective, longitudinal cohort study. Setting University cutaneous autoimmune disease clinic. Participants One hundred twenty-eight patients with cutaneous lupus erythematosus who presented from January 2007-July 2010 and had at least 2 visits with activity scores. Main Outcome Measures Response defined by 4-point or 20% decrease in activity score. Response to initiation determined with score before treatment and first visit at least 2 months after treatment. Response to continuation determined with score at first visit and most recent visit on treatment. Results Of 11 patients initiated on hydroxychloroquine, 55% were responders with a decrease in median (interquartile range) activity score from 8.0 (3.5-13) to 3.0 (1.8-7.3) (p=0.03). Of 15 patients who had failed hydroxychloroquine, 67% were responders to initiation of hydroxychloroquine-quinacrine, with a decrease in median (interquartile range) activity score from 6.0 (4.8-8.3) to 3.0 (0.75-5.0) (p=0.004). Nine out of 21 patients (43%) continued on hydroxychloroquine and 9 out of 21 patients (43%) continued on hydroxychloroquine-quinacrine were responders with a decrease in median (interquartile range) activity score from 6.0 (1.5-9.5) to 1.0 (0-4.5) (p=0.009) and 8.5 (4.25-17.5) to 5.0 (0.5-11.5) (p=0.01), respectively. Conclusion The use of quinacrine with hydroxychloroquine is associated with response in patients who fail hydroxychloroquine monotherapy. Further reduction in disease activity can be associated with continuation of antimalarials. PMID:21768444

Activating multi-ethnic youth for smoking prevention: design, baseline findings, and implementation of project SPLASH.

PubMed

Glanz, Karen; Lunde, Kevin B; Leakey, Tricia; Maddock, Jay; Koga, Karin; Yamauchi, Jessica; Maskarinec, Gertraud; Shigaki, Dorothy

2007-01-01

Achieving significant reductions in tobacco use by youth is an important challenge. There is a pressing need to develop and evaluate innovative strategies that stimulate youth involvement and are effective in multi-ethnic populations. This article describes an innovative tobacco prevention trial, and reports baseline characteristics of participants and findings about implementation of the curriculum. The aim of Project SPLASH is to evaluate the impact of a school-based smoking prevention intervention that emphasizes active involvement of middle school students, on rates of smoking initiation and regular smoking in a multi-ethnic cohort of youth in Hawaii. Project SPLASH is a group randomized trial that compares a 2-year innovative intervention with a social influence prevention program, in 20 public schools in Hawaii. The main outcome is mean 30-day smoking prevalence rates. The response rate was 78.4%. Approximately 1 in 4 students had tried smoking and 30-day smoking prevalence at baseline was 8%. Intervention and control groups were comparable in terms of tobacco use, gender, ethnicity, behavioral, environmental, and psychosocial characteristics. Differences in ethnic identification, socio-economic status, acculturation, and involvement in prevention activities may be due to chance. The intervention was well implemented by teachers across both the intervention and control school classes. For this study, 20 schools in Hawaii with close to 4000 participating students were recruited. Student smoking behavior and curriculum implementation were comparable by group status. The intervention study has the potential to elucidate how youth respond to an intervention with student involvement that incorporates cognitive and social action components.

Elevated sacroilac joint uptake ratios in systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Smet, A.A.; Mahmood, T.; Robinson, R.G.

1984-08-01

Sacroiliac joint radiographs and radionuclide sacroiliac joint uptake ratios were obtained on 14 patients with active systemic lupus erythematosus. Elevated joint ratios were found unilaterally in two patients and bilaterally in seven patients when their lupus was active. In patients whose disease became quiescent, the uptake ratios returned to normal. Two patients had persistently elevated ratios with continued clinical and laboratory evidence of active lupus. Mild sacroiliac joint sclerosis and erosions were detected on pelvic radiographs in these same two patients. Elevated quantitative sacroiliac joint uptake ratios may occur as a manifestation of active systemic lupus erythematosus.

Laboratory markers of cardiovascular risk in pediatric SLE: the APPLE baseline cohort.

PubMed

Ardoin, S P; Schanberg, L E; Sandborg, C; Yow, E; Barnhart, H X; Mieszkalski, K l; Ilowite, N T; von Scheven, E; Eberhard, A; Levy, D M; Kimura, Y; Silverman, E; Bowyer, S L; Punaro, L; Singer, N G; Sherry, D D; McCurdy, D; Klein-Gitelman, M; Wallace, C; Silver, R; Wagner-Weiner, L; Higgins, G C; Brunner, H I; Jung, L K; Imundo, L; Soep, J B; Reed, A M

2010-10-01

As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) (mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R(2) for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of

Knowledge of Parkinson's Disease in a Multiethnic Urban Asian Setting.

PubMed

Tan, Ai Huey; Tan, Chong Tin; Marras, Connie; Loh, Kwong Weng; Wye Ho, Niki Wai; Lim, Quan Hziung; Tan, Pei Wen; Lim, Chee Chean; Cheong, Yee Weai; Kong, Sik Thien; Schee, Jie Ping; Tan, Kean Hoong; Soo, Suet Ker; Vanderschaaf, Cheryl; Lai Heong Lew, Sara; Mahamad, Ummi Affah; Goh, Khean Jin; Yong, Hoi Sen; Lim, Shen-Yang

2015-01-01

Public knowledge regarding Parkinson's disease (PD) is important to facilitate good health-seeking behavior, but the literature on this topic is scarce. We aimed to explore the level of public knowledge regarding PD in a large multiethnic urban Asian cohort, and (as a secondary aim) in a smaller cohort of PD patients and caregivers. A Knowledge of PD Questionnaire (KPDQ) was developed and administered to members of the Malaysian general public, and to PD patients and caregivers. The KPDQ tests recognition of PD symptoms and general knowledge regarding PD. 1,258 members of the general public completed the KPDQ. Tremor was the most widely recognized symptom (recognized by 79.0% of respondents); however, 83.7% incorrectly believed that all PD patients experience tremor. Memory problem was the most widely recognized NMS. Overall, motor symptoms were better recognized than NMS. Common misperceptions were that there is a cure for PD (49.8%) and that PD is usually familial (41.4%). Female gender, Chinese ethnicity, tertiary education, healthcare-related work, and knowing someone with PD were independently associated with higher KPDQ scores. PD patients (n = 116) and caregivers (n = 135) demonstrated superior knowledge compared with the general public group, but one-third of them believed that PD is currently curable. This is the only study on public knowledge regarding PD in Asia. Important gaps in knowledge were evident, which could present a barrier to early diagnosis and appropriate treatment of PD. This highlights the need for targeted education campaigns and further research in this area.

The existential experience of everyday life with systemic lupus erythematosus.

PubMed

Larsen, Janni Lisander; Hall, Elisabeth O C; Jacobsen, Søren; Birkelund, Regner

2018-05-01

To explore from the perspective of women the nature of basic existential conditions while living with systemic lupus erythematosus. Systemic lupus erythematosus has an unpredictable disease course and is documented to cause an existential rearrangement of life. The significance of changes in existential conditions and related experiences are unclear in the context of nursing and women with systemic lupus erythematosus. A qualitative design guided by Van Manen's hermeneutic-phenomenological methodology. Individual in-depth interviews with 15 women diagnosed with systemic lupus erythematosus and of various ages, disease durations and severities were undertaken from September 2013 - October 2015. Data were analysed following van Manen's phenomenological approach and using drawing as an interpretive tool. The main existential experience was interpreted as a person "moving with the waves of systemic lupus erythematosus" constituted by the themes "oscillating between presence and absence of systemic lupus erythematosus," "recognizing space and bodily possibilities and limitations" and "being enriched through relationships and activities." When systemic lupus erythematosus was flaring, well-being was threatened and a laborious time to escape the feeling of a setback-in-life persisted long after the disease was medically under control. Daily life with systemic lupus erythematosus is conditioned by a prominent need to be in existential motion, related to the absence and presence of systemic lupus erythematosus. The experience of a setback-in-life by illness might challenge well-being and indicates that periods of disease flares or disturbing symptoms are critical time points to provide support. © 2018 John Wiley & Sons Ltd.

[Cardiac tamponade disclosing systemic lupus erythematosus].

PubMed

Nour-Eddine, M; Bennis, A; Soulami, S; Chraibi, N

1996-02-01

Cardiac tamponade secondary to systemic lupus erythematosus is rare and has a very serious prognosis. The authors report a case of cardiac tamponade confirmed by echocardiography, which constituted the presenting sign of systemic lupus erythematosus in a 20-year-old patient, who required emergency pericardial aspiration. The diagnosis of systemic lupus erythematosus was established on the basis of the combination of pericardial involvement, non-erosive arthritis, leukopenia with lymphopenia, presence of LE cells and anti-native DNA antibodies and positive antinuclear antibody titre of 1/2560. The clinical course was favourable in response to 3 months of corticosteroid treatment. The possibility of SLE should be considered in any case of cardiac tamponade in a young patient in which the aetiology is not explained.

Toll-like receptor activation in the pathogenesis of lupus nephritis.

PubMed

Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

2017-12-01

The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

LARGE-SCALE CO MAPS OF THE LUPUS MOLECULAR CLOUD COMPLEX

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tothill, N. F. H.; Loehr, A.; Stark, A. A.

2009-11-01

Fully sampled degree-scale maps of the {sup 13}CO 2-1 and CO 4-3 transitions toward three members of the Lupus Molecular Cloud Complex-Lupus I, III, and IV-trace the column density and temperature of the molecular gas. Comparison with IR extinction maps from the c2d project requires most of the gas to have a temperature of 8-10 K. Estimates of the cloud mass from {sup 13}CO emission are roughly consistent with most previous estimates, while the line widths are higher, around 2 km s{sup -1}. CO 4-3 emission is found throughout Lupus I, indicating widespread dense gas, and toward Lupus III andmore » IV. Enhanced line widths at the NW end and along the edge of the B 228 ridge in Lupus I, and a coherent velocity gradient across the ridge, are consistent with interaction between the molecular cloud and an expanding H I shell from the Upper-Scorpius subgroup of the Sco-Cen OB Association. Lupus III is dominated by the effects of two HAe/Be stars, and shows no sign of external influence. Slightly warmer gas around the core of Lupus IV and a low line width suggest heating by the Upper-Centaurus-Lupus subgroup of Sco-Cen, without the effects of an H I shell.« less

Predictors of intestinal pseudo-obstruction in systemic lupus erythematosus complicated by digestive manifestations: data from a Southern China lupus cohort.

PubMed

Huang, Q; Lai, W; Yuan, C; Shen, S; Cui, D; Zhao, J; Lin, J; Ren, H; Yang, M

2016-03-01

To determine factors that may predict intestinal pseudo-obstruction (IpsO) in systemic lupus erythematosus (SLE) patients complicated by digestive manifestations. SLE patients with digestive manifestations (n = 135) were followed at Southern Medical University affiliated Nanfang Hospital from 2000 until 2013. Demographic variables, clinical features, and laboratory data were compared between the two groups. Univariate and multivariate logistic regression models were used to establish factors that predispose to IpsO in these patients. At the end of the study period, 32 (23.7%) patients had developed IpsO. Mortality (9 patients) was infrequent and the cause of death was unrelated to IpsO. Independent predictors of IpsO in SLE were ureterectasia, anti-U1 RNP(+), peritonitis, and low C3 levels. Regular abdominal X-ray examinations are recommended in SLE patients with ureterectasia, anti-U1 RNP(+), peritonitis, or low C3 levels, as early diagnosis and therapy may prevent unnecessary surgical intervention and improve the disease course. © The Author(s) 2015.

Pathogenic mechanisms in systemic lupus erythematosus.

PubMed

Perl, Andras

2010-02-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the dysfunction of T cells, B cells, and dendritic cells and by the production of antinuclear autoantibodies. This editorial provides a synopsis of newly discovered genetic factors and signaling pathways in lupus pathogenesis that are documented in 11 state-of-the-art reviews and original articles. Mitochondrial hyperpolarization underlies mitochondrial dysfunction, depletion of ATP, oxidative stress, abnormal activation, and death signal processing in lupus T cells. The mammalian target of rapamycin, which is a sensor of the mitochondrial transmembrane potential, has been successfully targeted for treatment of SLE with rapamycin or sirolimus in both patients and animal models. Inhibition of oxidative stress, nitric oxide production, expression of endogenous retroviral and repetitive elements such as HRES-1, the long interspersed nuclear elements 1, Trex1, interferon alpha (IFN-alpha), toll-like receptors 7 and 9 (TLR-7/9), high-mobility group B1 protein, extracellular signal-regulated kinase, DNA methyl transferase 1, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, actin cytoskeleton formation, the nuclear factor kappa B pathway, and activation of cytotoxic T cells showed efficacy in animal models of lupus. Although B cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, human studies are currently ongoing to establish the value of several target molecules for treatment of patients with lupus. Ongoing oxidative stress and inflammation lead to accelerated atherosclerosis that emerged as a significant cause of mortality in SLE.

Minneapolis Multi-Ethnic Curriculum Project--Prejudice/Discrimination Unit.

ERIC Educational Resources Information Center

Skjervold, Christian K.; And Others

The student booklet presents short chapters illustrating the prejudice/discrimination unit of the Minneapolis Multi-Ethnic Curriculum Project for secondary schools. Fifteen brief chapters describe the ways Americans have and still do discriminate against the people of various ethnic groups. Topics cover the history and policies of the Know-Nothing…

A Cutaneous Lupus Erythematosus-Like Eruption Induced by Hydroxyurea.

PubMed

Yanes, Daniel A; Mosser-Goldfarb, Joy L

2017-01-01

Hydroxyurea is a medication with many well-described cutaneous side effects, notably the dermatomyositis-like eruption known as hydroxyurea dermopathy. Although systemic lupus erythematosus has been reported with hydroxyurea use, cutaneous lupus has not. We report a novel case of chronic cutaneous lupus induced by hydroxyurea and propose that this is a side effect that is distinct from hydroxyurea dermopathy. © 2016 Wiley Periodicals, Inc.

Discoid Lupus Erythematosus

MedlinePlus

... 1. In some patients with discoid lupus erythematosus, sunlight and cigarette smoking may make the lesions come ... be used. Patients whose condition is sensitive to sunlight need to wear a UVA/UVB blocking sunscreen ...

Risk Factors for Symptomatic Avascular Necrosis in Childhood-onset Systemic Lupus Erythematosus.

PubMed

Yang, Yelin; Kumar, Sathish; Lim, Lily Siok Hoon; Silverman, Earl D; Levy, Deborah M

2015-12-01

To examine the frequency and risk factors for symptomatic avascular necrosis (AVN) in childhood-onset systemic lupus erythematosus (cSLE). A single-center, nested, matched, case-control design was used. There were 617 patients with cSLE followed at the Hospital for Sick Children (SickKids) Lupus Clinic between July 1982 and June 2013 included in the study. The AVN cohort consisted of 37 patients identified with clinical findings of symptomatic AVN and diagnosis was confirmed by 1 or more imaging modalities. Three controls were matched to each patient with AVN by date and age at diagnosis. Baseline clinical, laboratory, and treatment characteristics were compared between patients with AVN and controls by univariable analyses and if statistically significant, were included in a multivariable logistic regression model. A total of 37/617 patients (6%) developed symptomatic AVN in 91 joints during followup at SickKids. The mean duration to disease was 2.3 years. The hip was the most commonly involved joint (26/37, 70%). Compared with the matched non-AVN cohort, patients with AVN had a higher incidence of central nervous system (CNS) involvement and nephritis, required greater cumulative prednisone (PRED) from cSLE diagnosis to AVN, received a greater maximal daily PRED dose, and had more frequent use of pulse methylprednisolone therapy. Multivariable regression analysis confirmed major organ involvement (CNS disease and/or nephritis) and maximal daily PRED dose as significant predictors of symptomatic AVN development. Patients with cSLE with severe organ involvement including nephritis and CNS disease and higher maximal daily dose of PRED are more likely to develop symptomatic AVN.

Screening and association testing of common coding variation in steroid hormone receptor co-activator and co-repressor genes in relation to breast cancer risk: the Multiethnic Cohort.

PubMed

Haiman, Christopher A; Garcia, Rachel R; Hsu, Chris; Xia, Lucy; Ha, Helen; Sheng, Xin; Le Marchand, Loic; Kolonel, Laurence N; Henderson, Brian E; Stallcup, Michael R; Greene, Geoffrey L; Press, Michael F

2009-01-30

Only a limited number of studies have performed comprehensive investigations of coding variation in relation to breast cancer risk. Given the established role of estrogens in breast cancer, we hypothesized that coding variation in steroid receptor coactivator and corepressor genes may alter inter-individual response to estrogen and serve as markers of breast cancer risk. We sequenced the coding exons of 17 genes (EP300, CCND1, NME1, NCOA1, NCOA2, NCOA3, SMARCA4, SMARCA2, CARM1, FOXA1, MPG, NCOR1, NCOR2, CALCOCO1, PRMT1, PPARBP and CREBBP) suggested to influence transcriptional activation by steroid hormone receptors in a multiethnic panel of women with advanced breast cancer (n = 95): African Americans, Latinos, Japanese, Native Hawaiians and European Americans. Association testing of validated coding variants was conducted in a breast cancer case-control study (1,612 invasive cases and 1,961 controls) nested in the Multiethnic Cohort. We used logistic regression to estimate odds ratios for allelic effects in ethnic-pooled analyses as well as in subgroups defined by disease stage and steroid hormone receptor status. We also investigated effect modification by established breast cancer risk factors that are associated with steroid hormone exposure. We identified 45 coding variants with frequencies > or = 1% in any one ethnic group (43 non-synonymous variants). We observed nominally significant positive associations with two coding variants in ethnic-pooled analyses (NCOR2: His52Arg, OR = 1.79; 95% CI, 1.05-3.05; CALCOCO1: Arg12His, OR = 2.29; 95% CI, 1.00-5.26). A small number of variants were associated with risk in disease subgroup analyses and we observed no strong evidence of effect modification by breast cancer risk factors. Based on the large number of statistical tests conducted in this study, the nominally significant associations that we observed may be due to chance, and will need to be confirmed in other studies. Our findings suggest that common coding

Metabolic Factors that Contribute to Lupus Pathogenesis

PubMed Central

Li, Wei; Sivakumar, Ramya; Titov, Anton A.; Choi, Seung-Chul; Morel, Laurence

2017-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease in which organ damage is mediated by pathogenic autoantibodies directed against nucleic acids and protein complexes. Studies in SLE patients and in mouse models of lupus have implicated virtually every cell type in the immune system in the induction or amplification of the autoimmune response as well as the promotion of an inflammatory environment that aggravates tissue injury. Here, we review the contribution of CD4+ T cells, B cells, and myeloid cells to lupus pathogenesis and then discuss alterations in the metabolism of these cells that may contribute to disease, given the recent advances in the field of immunometabolism. PMID:27480903

Lupus: When the Body Attacks Itself | NIH MedlinePlus the Magazine

MedlinePlus

... of this page please turn JavaScript on. Feature: Lupus Lupus: When the Body Attacks Itself Past Issues / Spring 2014 Table of Contents fast facts 1 Lupus occurs when the body's immune system attacks the ...

Disease evolution in late-onset and early-onset systemic lupus erythematosus.

PubMed

Aljohani, R; Gladman, D D; Su, J; Urowitz, M B

2017-10-01

Objective The objective of this study was to compare clinical features, disease activity, and outcome in late-onset versus early-onset systemic lupus erythematosus (SLE) over 5 years of follow up Method Patients with SLE since 1970 were followed prospectively according to standard protocol and tracked on a computerized database. Patients entering the cohort within one year of diagnosis constitute the inception cohort. Patients with late-onset (age at diagnosis ≥50) disease were identified and matched 1:2 based on gender and first clinic visit (±5) years with patients with early-onset disease (age at diagnosis 18-40 years). Results A total of 86 patients with late-onset disease (84.9% female, 81.4% Caucasian, mean age at SLE diagnosis ± SD 58.05 ± 7.30) and 169 patients with early-onset disease (86.4% female, 71% Caucasian, mean age at SLE diagnosis ± SD 27.80 ± 5.90) were identified. At enrollment, late-onset SLE patients had a lower total number of American College of Rheumatology (ACR) criteria, with less renal and neurologic manifestations. Mean SLE Disease Activity Index 2000 (SLEDAI-2K) scores were lower in late-onset SLE, especially renal features and anti-dsDNA positivity. Over 5 years, mean SLEDAI-2K scores decreased in both groups, while mean Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI) scores increased more significantly in the late-onset group; they developed more cardiovascular, renal, and ocular damage, and had higher prevalence of cardiovascular risk factors. Conclusion Although the late-onset SLE group had a milder presentation and less active disease, with the evolution of disease, they developed more organ damage likely as a consequence of cardiovascular risk factors and aging.

Cell death in the pathogenesis of systemic lupus erythematosus and lupus nephritis.

PubMed

Mistry, Pragnesh; Kaplan, Mariana J

2017-12-01

Nephritis is one of the most severe complications of systemic lupus erythematosus (SLE). One key characteristic of lupus nephritis (LN) is the deposition of immune complexes containing nucleic acids and/or proteins binding to nucleic acids and autoantibodies recognizing these molecules. A variety of cell death processes are implicated in the generation and externalization of modified nuclear autoantigens and in the development of LN. Among these processes, apoptosis, primary and secondary necrosis, NETosis, necroptosis, pyroptosis, and autophagy have been proposed to play roles in tissue damage and immune dysregulation. Cell death occurs in healthy individuals during conditions of homeostasis yet autoimmunity does not develop, at least in part, because of rapid clearance of dying cells. In SLE, accelerated cell death combined with a clearance deficiency may lead to the accumulation and externalization of nuclear autoantigens and to autoantibody production. In addition, specific types of cell death may modify autoantigens and alter their immunogenicity. These modified molecules may then become novel targets of the immune system and promote autoimmune responses in predisposed hosts. In this review, we examine various cell death pathways and discuss how enhanced cell death, impaired clearance, and post-translational modifications of proteins could contribute to the development of lupus nephritis. Published by Elsevier Inc.

Clinical associations of proinflammatory cytokines, oxidative biomarkers and vitamin D levels in systemic lupus erythematosus.

PubMed

Willis, R; Smikle, M; DeCeulaer, K; Romay-Penabad, Z; Papalardo, E; Jajoria, P; Harper, B; Murthy, V; Petri, M; Gonzalez, E B

2017-12-01

Background The abnormal biological activity of cytokines plays an important role in the pathophysiology of both systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Several studies have highlighted the association of vitamin D and certain pro-inflammatory cytokines with disease activity in SLE. However, there are limited data on the association of vitamin D and antiphospholipid antibodies (aPL) with various proinflammatory biomarkers in these patients and their relative impact on clinical outcomes. Methods The serum levels of several aPL, 25-hydroxy-vitamin D, pro-inflammatory cytokines including IFNα, IL-1β, IL-6, IL-8, IP10, sCD40L, TNFα and VEGF were measured in 312 SLE patients from the Jamaican ( n = 45) and Hopkins ( n = 267) lupus cohorts using commercial Milliplex and ELISA assays. Oxidized LDL/β2glycoprotein antigenic complexes (oxLβ2Ag) and their associated antibodies were also measured in the Jamaican cohort. Healthy controls for oxidative marker and cytokine testing were used. Results Abnormally low vitamin D levels were present in 61.4% and 73.3% of Hopkins and Jamaican SLE patients, respectively. Median concentrations of IP10, TNFα, sCD40L and VEGF were elevated in both cohorts, oxLβ2Ag and IL-6 were elevated in the Jamaican cohort, and IFNα, IL-1β and IL-8 were the same or lower in both cohorts compared to controls. IP10 and VEGF were independent predictors of disease activity, aPL, IP10 and IL-6 were independent predictors of thrombosis and IL-8, and low vitamin D were independent predictors of pregnancy morbidity despite there being no association of vitamin D with pro-inflammatory cytokines. Conclusions Our results indicate that aPL-mediated pro-inflammatory cytokine production is likely a major mechanism of thrombus development in SLE patients. We provide presumptive evidence of the role IL-8 and hypovitaminosis D play in obstetric pathology in SLE but further studies are required to characterize the subtle

Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.

PubMed

Zhao, Yu-Kun; Wang, Fang; Chen, Wen-Na; Xu, Rui; Wang, Zhuo; Jiang, Yuan-Wen; Luo, Di-Qing; Han, Jian-De

2016-04-01

Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.

Is antibody clustering predictive of clinical subsets and damage in systemic lupus erythematosus?

PubMed

To, C H; Petri, M

2005-12-01

To examine autoantibody clusters and their associations with clinical features and organ damage accrual in patients with systemic lupus erythematosus (SLE). The study group comprised 1,357 consecutive patients with SLE who were recruited to participate in a prospective longitudinal cohort study. In the cohort, 92.6% of the patients were women, the mean +/- SD age of the patients was 41.3 +/- 12.7 years, 55.9% were Caucasian, 39.1% were African American, and 5% were Asian. Seven autoantibodies (anti-double-stranded DNA [anti-dsDNA], anti-Sm, anti-Ro, anti-La, anti-RNP, lupus anticoagulant (LAC), and anticardiolipin antibody [aCL]) were selected for cluster analysis using the K-means cluster analysis procedure. Three distinct autoantibody clusters were identified: cluster 1 (anti-Sm and anti-RNP), cluster 2 (anti-dsDNA, anti-Ro, and anti-La), and cluster 3 (anti-dsDNA, LAC, and aCL). Patients in cluster 1 (n = 451), when compared with patients in clusters 2 (n = 470) and 3 (n = 436), had the lowest incidence of proteinuria (39.7%), anemia (52.8%), lymphopenia (33.9%), and thrombocytopenia (13.7%). The incidence of nephrotic syndrome and leukopenia was also lower in cluster 1 than in cluster 2. Cluster 2 had the highest female-to-male ratio (22:1) and the greatest proportion of Asian patients. Among the 3 clusters, cluster 2 had significantly more patients presenting with secondary Sjögren's syndrome (15.7%). Cluster 3, when compared with the other 2 clusters, consisted of more Caucasian and fewer African American patients and was characterized by the highest incidence of arterial thrombosis (17.4%), venous thrombosis (25.7%), and livedo reticularis (31.4%). By using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, the greatest frequency of nephrotic syndrome (8.9%) was observed in patients in cluster 2, whereas cluster 3 patients had the highest percentage of damage due to cerebrovascular accident (12.8%) and

Rationale, design, and methods for Canadian alliance for healthy hearts and minds cohort study (CAHHM) - a Pan Canadian cohort study.

PubMed

Anand, Sonia S; Tu, Jack V; Awadalla, Philip; Black, Sandra; Boileau, Catherine; Busseuil, David; Desai, Dipika; Després, Jean-Pierre; de Souza, Russell J; Dummer, Trevor; Jacquemont, Sébastien; Knoppers, Bartha; Larose, Eric; Lear, Scott A; Marcotte, Francois; Moody, Alan R; Parker, Louise; Poirier, Paul; Robson, Paula J; Smith, Eric E; Spinelli, John J; Tardif, Jean-Claude; Teo, Koon K; Tusevljak, Natasa; Friedrich, Matthias G

2016-07-27

The Canadian Alliance for Healthy Hearts and Minds (CAHHM) is a pan-Canadian, prospective, multi-ethnic cohort study being conducted in Canada. The overarching objective of the CAHHM is to understand the association of socio-environmental and contextual factors (such as societal structure, activity, nutrition, social and tobacco environments, and access to health services) with cardiovascular risk factors, subclinical vascular disease, and cardiovascular and other chronic disease outcomes. Participants between 35 and 69 years of age are being recruited from existing cohorts and a new First Nations Cohort to undergo a detailed assessment of health behaviours (including diet and physical activity), cognitive function, assessment of their local home and workplace environments, and their health services access and utilization. Physical measures including weight, height, waist/hip circumference, body fat percentage, and blood pressure are collected. In addition, eligible participants undergo magnetic resonance imaging (MRI) of the brain, heart, carotid artery and abdomen to detect early subclinical vascular disease and ectopic fat deposition. CAHHM is a prospective cohort study designed to investigate the impact of community level factors, individual health behaviours, and access to health services, on cognitive function, subclinical vascular disease, fat distribution, and the development of chronic diseases among adults living in Canada.

Disease features and outcomes in United States lupus patients of Hispanic origin and their Mestizo counterparts in Latin America: a commentary.

PubMed

Ugarte-Gil, Manuel F; Pons-Estel, Guillermo J; Molineros, Julio; Wojdyla, Daniel; McGwin, Gerald; Nath, Swapan K; Pons-Estel, Bernardo A; Alarcón-Riquelme, Marta; Alarcón, Graciela S

2016-03-01

To evaluate disease features and outcomes in two populations with significant Amerindian ancestry. Hispanic patients (from Texas) from the Lupus in Minorities: Nature versus Nurture (LUMINA) cohort and Mestizo patients from the Grupo Latino Americano De Estudio del Lupus or Latin American Group for the Study of Lupus (GLADEL) cohort were included. Disease features and outcomes were evaluated at baseline and last visit. Admixture informative markers of Mestizo Genoma de Lupus Eritematoso Sistémico Network consortium (GENLES) patients and Hispanic LUMINA patients were compared. Univariable analyses were performed using Chi square or Student's t test as appropriate. Multivariable analyses adjusting for possible confounders were carried out using Poisson, logistic or Cox regression models as appropriate. A total of 114 LUMINA and 619 GLADEL patients were included. GLADEL patients had accrued more damage at baseline, but the opposite was the case at last visit. Being from LUMINA was a risk factor for damage accrual, even after adjusting for possible confounders [relative risk (RR) 1.33, 95% CI 1.12, 1.58]. Also, LUMINA patients have a higher risk of mortality than GLADEL patients [hazard ratio (HR) 2.37, 95% CI 1.10, 5.15], having 5-year survival of 85.6% and 94.5%, respectively. In addition, 79 LUMINA patients and 744 Mestizo GENLES patients were evaluated in order to compare genetic ancestry between the two groups; GENLES patients had a higher proportion of European ancestry (48.5% vs 43.3%, P = 0.003) and a lower proportion of Asian ancestry (3.7% vs 4.9%, P = 0.048), but the proportions of Amerindian and African ancestry were comparable in both. USA Hispanic patients seemed to have a poorer prognosis than their counterparts from Latin America, despite having a comparable genetic background. Socioeconomic factors may account for these observations. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights

An invisible student population: Accommodating and serving college students with lupus.

PubMed

Agarwal, Neelam; Kumar, Vinod

2017-01-01

Systemic Lupus Erythematosus (SLE), or lupus, is a chronic autoimmune disorder. Individuals with lupus face unique psychosocial and emotional challenges such as living with the unpredictability of the disease, symptoms such as fatigue, pain and depression, anxiety, cognitive problems, and coping with stress. This article attempts to shed light on the role that lupus plays in the lives of college students in their academics and other unique psychosocial needs. The author uses a single case study method based on the lived experience of a student with lupus. The method adopted is used as a means to provide anecdotal information about specific areas to consider when providing services to students living with this condition. Findings from this one case study identified some of the accommodations available to help students in higher education that may even vary for two students with same diagnosis of lupus. The paper presents some of the innovative strategies that can be used by practitioners while working with these students in higher education. These strategies can provide helpful support for students with lupus with the recommended academic accommodations.

Kidney allograft survival of African American and Caucasian American recipients with lupus.

PubMed

Contreras, G; Li, H; Gonzalez-Suarez, M; Isakova, T; Scialla, J J; Pedraza, F; Mattiazzi, A; Diaz-Wong, R; Sageshima, J; Brito, Y; Guerra, G; Acevedo, B; Sajid Ali, A; Kershaw, T J; Chen, L; Burke, G W; Kupin, W; Ciancio, G; Roth, D

2014-02-01

African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well (p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of prior kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch, blood type compatibility, transplant Era, and follow-up time. Contrary to the unmatched cohort with significantly higher allograft failure rate (events per 100 patient-years) in African Americans compared to Caucasian Americans (10.49 vs 6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81, p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39, p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and mortality (2.79 vs 3.52, p=0.097). In lupus recipients of kidney transplants from deceased donors, African American and Caucasian Americans have similar allograft failure rates when predictors are matched between groups.

Risk factors for congenital anomaly in a multiethnic birth cohort: an analysis of the Born in Bradford study.

PubMed

Sheridan, Eamonn; Wright, John; Small, Neil; Corry, Peter C; Oddie, Sam; Whibley, Catherine; Petherick, Emily S; Malik, Teena; Pawson, Nicole; McKinney, Patricia A; Parslow, Roger C

2013-10-19

Congenital anomalies are a leading cause of infant death and disability and their incidence varies between ethnic groups in the UK. Rates of infant death are highest in children of Pakistani origin, and congenital anomalies are the most common cause of death in children younger than 12 in this ethnic group. We investigated the incidence of congenital anomalies in a large multiethnic birth cohort to identify the causes of the excess of congenital anomalies in this community. We obtained questionnaire data from the mothers of children with one or more anomalies from the Born in Bradford study, a prospective birth cohort study of 13,776 babies and their families in which recruitment was undertaken between 2007 and 2011. Details of anomalies were prospectively reported to the study and we cross checked these details against medical records. We linked data for anomalies to maternal questionnaire and clinical data gathered as part of the Born in Bradford study. We calculated univariate and multivariate risk ratios (RRs) with 95% CIs for various maternal risk factors. Of 11,396 babies for whom questionnaire data were available, 386 (3%) had a congenital anomaly. Rates for congenital anomaly were 305·74 per 10,000 livebirths, compared with a national rate of 165·90 per 10,000. The risk was greater for mothers of Pakistani origin than for those of white British origin (univariate RR 1·96, 95% CI 1·56-2·46). Overall, 2013 (18%) babies were the offspring of first-cousin unions. These babies were mainly of Pakistani origin--1922 (37%) of 5127 babies of Pakistani origin had parents in first-cousin unions. Consanguinity was associated with a doubling of risk for congenital anomaly (multivariate RR 2·19, 95% CI 1·67-2·85); we noted no association with increasing deprivation. 31% of all anomalies in children of Pakistani origin could be attributed to consanguinity. We noted a similar increase in risk for mothers of white British origin older than 34 years (multivariate RR

Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21.

PubMed

Hughes, Travis; Kim-Howard, Xana; Kelly, Jennifer A; Kaufman, Kenneth M; Langefeld, Carl D; Ziegler, Julie; Sanchez, Elena; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D; Martín, Javier; Brown, Elizabeth E; Vilá, Luis M; Alarcón, Graciela S; James, Judith A; Gilkeson, Gary S; Moser, Kathy L; Gaffney, Patrick M; Merrill, Joan T; Vyse, Timothy J; Alarcón-Riquelme, Marta E; Nath, Swapan K; Harley, John B; Sawalha, Amr H

2011-06-01

Genetic association of the IL2/IL21 region at chromosome 4q27 has previously been reported in lupus and a number of autoimmune and inflammatory diseases. This study was undertaken to determine whether this genetic effect could be localized, using a very large cohort of lupus patients and controls. We genotyped 45 tag single-nucleotide polymorphisms (SNPs) across the IL2/IL21 locus in 2 large independent lupus sample sets. We studied a set of subjects of European descent consisting of 4,248 lupus patients and 3,818 healthy controls, and an African American set of 1,569 patients and 1,893 healthy controls. Imputation in 3,004 additional controls from the Wellcome Trust Case Control Consortium was also performed. Genetic association between the genotyped markers was determined, and pairwise conditional analysis was performed to localize the independent genetic effect in the IL2/IL21 locus in lupus. We established and confirmed the genetic association between IL2/IL21 and lupus. Using conditional analysis and transethnic mapping, we localized the genetic effect in this locus to 2 SNPs in high linkage disequilibrium: rs907715 located within IL21 (odds ratio 1.16 [95% confidence interval 1.10-1.22], P=2.17×10(-8)) and rs6835457 located in the 3'-untranslated flanking region of IL21 (odds ratio 1.11 [95% confidence interval 1.05-1.17], P=9.35×10(-5)). Our findings establish the genetic association between lupus and IL2/IL21 with a genome-wide level of significance. Further, our findings indicate that this genetic association within the IL2/IL21 linkage disequilibrium block is localized to IL21. If other autoimmune IL2/IL21 genetic associations are similarly localized, then the IL21 risk alleles would be predicted to operate by a fundamental mechanism that influences the course of a number of autoimmune disease processes. Copyright © 2011 by the American College of Rheumatology.

Bibliography of Multi-Ethnic and Sex-Fair Resource Materials.

ERIC Educational Resources Information Center

Massachusetts State Dept. of Education, Boston. Bureau of Equal Educational Opportunities.

This annotated bibliography lists both nondiscriminatory instructional materials (largely audio-visual) for classroom use and works for teachers' use that promote multi-ethnic and sex fair education. The materials listed include films, filmstrips, slide presentations and video tapes, bibliographies of curriculum materials, books, handbooks and…

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study.

PubMed

Rebello, Salome A; Chen, Cynthia H; Naidoo, Nasheen; Xu, Wang; Lee, Jeannette; Chia, Kee Seng; Tai, E Shyong; van Dam, Rob M

2011-06-02

Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation. We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139). After adjusting for multiple confounders, we observed inverse associations between coffee and HOMA-IR (percent difference: - 8.8% for ≥ 3 cups/day versus rarely or never; Ptrend = 0.007), but no significant associations between coffee and inflammatory markers. Tea consumption was not associated with glycemic markers, but green tea was inversely associated with plasma C-reactive protein concentrations (percent difference: - 12.2% for ≥ 1 cup/day versus < 1 cup/week; Ptrend = 0.042). These data provide additional evidence for a beneficial effect of habitual caffeinated coffee consumption on insulin sensitivity, and suggest that this effect is unlikely to be mediated by anti-inflammatory mechanisms.

Retinal nerve fiber layer thickness and neuropsychiatric manifestations in systemic lupus erythematosus.

PubMed

Shulman, S; Shorer, R; Wollman, J; Dotan, G; Paran, D

2017-11-01

Background Cognitive impairment is frequent in systemic lupus erythematosus. Atrophy of the corpus callosum and hippocampus have been reported in patients with systemic lupus erythematosus, and diffusion tensor imaging studies have shown impaired white matter integrity, suggesting that white matter damage in systemic lupus erythematosus may underlie the cognitive impairment as well as other neuropsychiatric systemic lupus erythematosus manifestations. Retinal nerve fiber layer thickness, as assessed by optical coherence tomography, has been suggested as a biomarker for white matter damage in neurologic disorders such as multiple sclerosis, Alzheimer's disease and Parkinson's disease. Retinal nerve fiber layer thinning may occur early, even in patients with mild clinical symptoms. Aim The objective of this study was to assess the association of retinal nerve fiber layer thickness, as a biomarker of white matter damage in systemic lupus erythematosus patients, with neuropsychiatric systemic lupus erythematosus manifestations, including cognitive impairment. Methods Twenty-one consecutive patients with systemic lupus erythematosus underwent neuropsychological testing using a validated computerized battery of tests as well as the Rey-Auditory verbal learning test. All 21 patients, as well as 11 healthy, age matched controls, underwent optical coherence tomography testing to assess retinal nerve fiber layer thickness. Correlations between retinal nerve fiber layer thickness and results in eight cognitive domains assessed by the computerized battery of tests as well as the Rey-Auditory verbal learning test were assessed in patients with systemic lupus erythematosus, with and without neuropsychiatric systemic lupus erythematosus, and compared to retinal nerve fiber layer thickness in healthy controls. Results No statistically significant correlation was found between retinal nerve fiber layer thickness in patients with systemic lupus erythematosus as compared to healthy

Higher Maternal Dietary Protein Intake Is Associated with a Higher Risk of Gestational Diabetes Mellitus in a Multiethnic Asian Cohort.

PubMed

Pang, Wei Wei; Colega, Marjorelee; Cai, Shirong; Chan, Yiong Huak; Padmapriya, Natarajan; Chen, Ling-Wei; Soh, Shu-E; Han, Wee Meng; Tan, Kok Hian; Lee, Yung Seng; Saw, Seang-Mei; Gluckman, Peter D; Godfrey, Keith M; Chong, Yap-Seng; van Dam, Rob M; Chong, Mary Ff

2017-04-01

Background: Dietary protein may affect glucose metabolism through several mechanisms, but results from studies on dietary protein intake and risk of gestational diabetes mellitus (GDM) have been inconsistent. Objective: We examined the cross-sectional associations of dietary protein intake from different food sources during pregnancy with the risk of GDM in a multiethnic Asian population. Methods: We included 980 participants with singleton pregnancies from the Growing Up in Singapore Toward healthy Outcomes (GUSTO) cohort. Protein intake was ascertained from 24-h dietary recall and 3-d food diaries at 26-28 wk gestation. GDM was defined as fasting glucose ≥7.0 mmol/L and/or 2-h postload glucose ≥7.8 mmol/L at 26-28 wk gestation. We evaluated the association of dietary protein intake with GDM risk by substituting carbohydrate with protein in an isocaloric model with the use of multivariable logistic regression analysis. Results: The prevalence of GDM was 17.9% among our participants. After adjustment for potential confounders, a higher total dietary protein intake was associated with a higher risk of GDM; the OR comparing the highest with the lowest quartile of intake was 2.15 (95% CI: 1.27, 3.62; P -trend = 0.016). Higher intake levels of both animal protein (OR: 2.87; 95% CI: 1.58, 5.20; P -trend = 0.001) and vegetable protein (OR: 1.78; 95% CI: 0.99, 3.20; P -trend = 0.009) were associated with a higher risk of GDM. Among the animal protein sources, higher intake levels of seafood protein (OR: 2.17; 95% CI: 1.26, 3.72; P -trend = 0.023) and dairy protein (OR: 1.87; 95% CI: 1.11, 3.15; P -trend = 0.017) were significantly associated with a higher GDM risk. Conclusion: Higher intake levels of both animal and vegetable protein were associated with a higher risk of GDM in Asian women. This trial was registered at clinicaltrials.gov as NCT01174875. © 2017 American Society for Nutrition.

Induction of lupus autoantibodies by adjuvants

USGS Publications Warehouse

Satoh, M.; Kuroda, Y.; Yoshida, H.; Behney, K.M.; Mizutani, A.; Akaogi, J.; Nacionales, D.C.; Lorenson, T.D.; Rosenbauer, R.J.; Reeves, W.H.

2003-01-01

Exposure to the hydrocarbon oil pristane induces lupus specific autoantibodies in non-autoimmune mice. We investigated whether the capacity to induce lupus-like autoimmunity is a unique property of pristane or is shared by other adjuvant oils. Seven groups of 3-month-old female BALB/cJ mice received a single intraperitoneal injection of pristane, squalene (used in the adjuvant MF59), incomplete Freund's adjuvant (IFA), three different medicinal mineral oils, or saline, respectively. Serum autoantibodies and peritoneal cytokine production were measured. In addition to pristane, the mineral oil Bayol F (IFA) and the endogenous hydrocarbon squalene both induced anti-nRNP/Sm and -Su autoantibodies (20% and 25% of mice, respectively). All of these hydrocarbons had prolonged effects on cytokine production by peritoneal APCs. However, high levels of IL-6, IL-12, and TNF?? production 2-3 months after intraperitoneal injection appeared to be associated with the ability to induce lupus autoantibodies. The ability to induce lupus autoantibodies is shared by several hydrocarbons and is not unique to pristane. It correlates with stimulation of the production of IL-12 and other cytokines, suggesting a relationship with a hydrocarbon's adjuvanticity. The potential to induce autoimmunity may complicate the use of oil adjuvants in human and veterinary vaccines. ?? 2003 Elsevier Ltd. All rights reserved.

4G/5G plasminogen activator inhibitor-1 and -308 A/G tumor necrosis factor-α promoter gene polymorphisms in Argentinean lupus patients: focus on lupus nephritis.

PubMed

Muñoz, Sebastián Andrés; Aranda, Federico; Allievi, Alberto; Orden, Alberto Omar; Perés Wingeyer, Silvia; Trobo, Rosana; Alvarez, Analía; Eimon, Alicia; Barreira, Juan Carlos; Schneeberger, Emilce; Dal Pra, Fernando; Sarano, Judith; Hofman, Julio; Chamorro, Julián; de Larrañaga, Gabriela

2014-02-01

We investigated the relationship between the 4G/5G plasminogen activator inhibitor (PAI-1) and -308 A/G tumor necrosis factor-α (TNF-α) polymorphisms and the clinical and biochemical features of systemic lupus erythematosus (SLE) in an Argentinean patient cohort. A total of 402 patients were studied, including 179 SLE patients and 223 healthy individuals. PCR-RLFP was used to determine the genotypes of the 4G/5G PAI-1 and -308 A/G TNF-α polymorphisms. SLE patients with lupus nephritis (LN) (n = 86) were compared with patients without LN (n = 93). Additionally, LN patients were divided into proliferative LN and non-proliferative LN groups according to the results of the renal biopsies. No significant differences were noted in the genotype distributions or allele frequencies of these TNF-α and PAI-1 polymorphisms between SLE patients and controls. There were higher numbers of criteria for SLE, more lupus flares and higher damage scores in LN patients, but there were similar frequencies of anti-phospholipid antibody (APA) positivity and anti-phospholipid syndrome. No significant difference was noted for any studied variable between the proliferative LN and non-proliferative LN groups except for the presence of APA. We found no significant differences in the TNF-α and PAI-1 genotype distributions or allele frequencies between groups. We found that the -308 A/G TNF-α and 4G/5G PAI-1 polymorphisms are not associated with susceptibility to SLE in an Argentinean population. We also did not find any association between the presence of any specific allele or genotype and the development of LN in SLE patients. Finally, no association was noted between either of the two polymorphisms and the severity of renal disease.

Cancer complicating systemic lupus erythematosus--a dichotomy emerging from a nested case-control study.

PubMed

Dey, D; Kenu, E; Isenberg, D A

2013-08-01

We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified.

Dynamics of change in multiethnic societies: An archaeological perspective from colonial North America.

PubMed

Lightfoot, Kent G

2015-07-28

This Perspective presents an overview of the archaeology of pluralistic colonies (approximately late 1500s-1800s) in North America. It complements the other special feature papers in this issue on ancient societies in Mesoamerica, the Near East, the Armenian Highlands, Peru, and China by presenting another body of literature for examining the dynamics of change in multiethnic societies from a different time and place. In synthesizing archaeological investigations of mercantile, plantation, and missionary colonies, this Perspective shows how this research is relevant to the study of pluralism in both historic and ancient societies in three ways. (i) It enhances our understanding of interethnic relationships that took place in complex societies with imposing political hierarchies and labor structures. (ii) It helps us to refine the methods used by archaeologists to define and analyze multiethnic communities that were spatially delimited by ethnic neighborhoods. Finally, (iii) it presents more than a half century of experimentation with various models (e.g., acculturation, creolization, ethnogenesis, and hybridity) that have been used to study the dynamics of culture change in multiethnic societies.

Dynamics of change in multiethnic societies: An archaeological perspective from colonial North America

PubMed Central

Lightfoot, Kent G.

2015-01-01

This Perspective presents an overview of the archaeology of pluralistic colonies (approximately late 1500s–1800s) in North America. It complements the other special feature papers in this issue on ancient societies in Mesoamerica, the Near East, the Armenian Highlands, Peru, and China by presenting another body of literature for examining the dynamics of change in multiethnic societies from a different time and place. In synthesizing archaeological investigations of mercantile, plantation, and missionary colonies, this Perspective shows how this research is relevant to the study of pluralism in both historic and ancient societies in three ways. (i) It enhances our understanding of interethnic relationships that took place in complex societies with imposing political hierarchies and labor structures. (ii) It helps us to refine the methods used by archaeologists to define and analyze multiethnic communities that were spatially delimited by ethnic neighborhoods. Finally, (iii) it presents more than a half century of experimentation with various models (e.g., acculturation, creolization, ethnogenesis, and hybridity) that have been used to study the dynamics of culture change in multiethnic societies. PMID:25870288

Bilateral periorbital edema in systemic lupus erythematosus.

PubMed

Norden, D; Weinberg, J; Schumacher, H R; Keenan, G; Freundlich, B

1993-12-01

Periorbital edema is a rare manifestation of systemic lupus erythematosus (SLE). We describe a patient with SLE who developed bilateral periorbital edema during her lupus flares. Conjunctival biopsy confirmed the presence of inflammation. Resolution occurred only after high doses of corticosteroids. The differential diagnosis of periorbital edema and possible etiologies of the edema are briefly discussed.

Hypoparathyroidism associated with systemic lupus erythematosus.

PubMed

Gazarian, M; Laxer, R M; Kooh, S W; Silverman, E D

1995-11-01

We describe a 15-year-old girl with systemic lupus erythematosus (SLE) who presented with hypocalcemia and a generalized seizure in the setting of an intercurrent illness and active central nervous system lupus. She was subsequently found to have idiopathic hypoparathyroidism. The association of SLE with hypoparathyroidism is extremely rare and this case represents the first pediatric report of this rare association. We suggest there may be a common underlying pathophysiological process linking these diseases.

Intravenous Immunoglobulin in the Management of Lupus Nephritis

PubMed Central

Wenderfer, Scott E.; Thacker, Trisha

2012-01-01

The occurrence of nephritis in patients with systemic lupus erythematosus is associated with increased morbidity and mortality. The pathogenesis of lupus nephritis is complex, involving innate and adaptive cellular and humoral immune responses. Autoantibodies in particular have been shown to be critical in the initiation and progression of renal injury, via interactions with both Fc-receptors and complement. One approach in the management of patients with lupus nephritis has been the use of intravenous immunoglobulin. This therapy has shown benefit in the setting of many forms of autoantibody-mediated injury; however, the mechanisms of efficacy are not fully understood. In this paper, the data supporting the use of immunoglobulin therapy in lupus nephritis will be evaluated. In addition, the potential mechanisms of action will be discussed with respect to the known involvement of complement and Fc-receptors in the kidney parenchyma. Results are provocative and warrant additional clinical trials. PMID:23056926

Type I Interferon in the Pathogenesis of Lupus

PubMed Central

Crow, Mary K.

2014-01-01

Investigations of patients with systemic lupus erythematosus (SLE) have applied insights from studies of the innate immune response to define type I interferon (IFN-I), with IFN-α the dominant mediator, as central to the pathogenesis of this prototype systemic autoimmune disease. Genetic association data identify regulators of nucleic acid degradation and components of TLR-independent, endosomal TLR-dependent, and IFN-I signaling pathways as contributors to lupus disease susceptibility. Together with a gene expression signature characterized by IFNI-induced gene transcripts in lupus blood and tissue, those data support the conclusion that many of the immunologic and pathologic features of this disease are a consequence of a persistent self-directed immune reaction driven by IFN-I and mimicking a sustained anti-virus response. This expanding knowledge of the role of IFN-I and the innate immune response suggests candidate therapeutic targets that are being tested in lupus patients. PMID:24907379

White matter lesions and brain atrophy in systemic lupus erythematosus patients: correlation to cognitive dysfunction in a cohort of systemic lupus erythematosus patients using different definition models for neuropsychiatric systemic lupus erythematosus.

PubMed

Cannerfelt, B; Nystedt, J; Jönsen, A; Lätt, J; van Westen, D; Lilja, A; Bengtsson, A; Nilsson, P; Mårtensson, J; Sundgren, P C

2018-06-01

Aim The aim of this study was to evaluate the extent of white matter lesions, atrophy of the hippocampus and corpus callosum, and their correlation with cognitive dysfunction (CD), in patients diagnosed with systemic lupus erythematosus (SLE). Methods Seventy SLE patients and 25 healthy individuals (HIs) were included in the study. To evaluate the different SLE and neuropsychiatric SLE (NPSLE) definition schemes, patients were grouped both according to the American College of Rheumatology (ACR) definition, as well as the more stringent ACR-Systemic Lupus International Collaborating Clinics definition. Patients and HIs underwent a 3 Tesla brain MRI and a standardized neuropsychological test. MRI data were evaluated for number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum. Differences between groups and subgroups were evaluated for significance. Number and volume of white matter lesions and atrophy of the hippocampus and corpus callosum were correlated to cognitive dysfunction. Results The total volume of white matter lesions was significantly larger in SLE patients compared to HIs ( p = 0.004). However, no significant differences were seen between the different SLE subgroups. Atrophy of the bilateral hippocampus was significantly more pronounced in patients with NPSLE compared to those with non-NPSLE (right: p = 0.010; left p = 0.023). Significant negative correlations between cognitive test scores on verbal memory and number and volume of white matter lesions were present. Conclusion SLE patients have a significantly larger volume of white matter lesions on MRI compared to HIs and the degree of white matter lesion volume correlates to cognitive dysfunction, specifically to verbal memory. No significant differences in the number or volume of white matter lesions were identified between subgroups of SLE patients regardless of the definition model used.

Breakdown of Immune Tolerance in Systemic Lupus Erythematosus by Dendritic Cells

PubMed Central

Reihl, Alec M.

2016-01-01

Dendritic cells (DC) play an important role in the pathogenesis of systemic lupus erythematosus (SLE), an autoimmune disease with multiple tissue manifestations. In this review, we summarize recent studies on the roles of conventional DC and plasmacytoid DC in the development of both murine lupus and human SLE. In the past decade, studies using selective DC depletions have demonstrated critical roles of DC in lupus progression. Comprehensive in vitro and in vivo studies suggest activation of DC by self-antigens in lupus pathogenesis, followed by breakdown of immune tolerance to self. Potential treatment strategies targeting DC have been developed. However, many questions remain regarding the mechanisms by which DC modulate lupus pathogenesis that require further investigations. PMID:27034965

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus.

PubMed

Salphale, P; Danda, D; Chandrashekar, L; Peter, D; Jayaseeli, N; George, R

2011-12-01

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

Cancer risk in childhood-onset systemic lupus.

PubMed

Bernatsky, Sasha; Clarke, Ann E; Labrecque, Jeremy; von Scheven, Emily; Schanberg, Laura E; Silverman, Earl D; Brunner, Hermine I; Haines, Kathleen A; Cron, Randy Q; O'Neil, Kathleen M; Oen, Kiem; Rosenberg, Alan M; Duffy, Ciarán M; Joseph, Lawrence; Lee, Jennifer L; Kale, Mruganka; Turnbull, Elizabeth M; Ramsey-Goldman, Rosalind

2013-01-01

The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. There were 1020 patients aged <18 at cohort entry. Most (82%) were female and Caucasian; mean age at cohort entry was 12.6 years (standard deviation (SD) = 3.6). Subjects were observed for a total of 7,986 (average 7.8) patient-years. Within this interval, only three invasive cancers were expected. However, 14 invasive cancers occurred with an SIR of 4.7, 95% confidence interval (CI) 2.6 to 7.8. Three hematologic cancers were found (two non-Hodgkin’s lymphoma, one leukemia), for an SIR of 5.2 (95% CI 1.1 to 15.2). The SIRs stratified by age group and sex, were similar across these strata. There was a trend for highest cancer occurrence 10 to 19 years after SLE diagnosis. These results suggest an increased cancer risk in pediatric onset SLE versus the general population. In absolute terms, this represents relatively few events. Of note, risk may be highest only after patients have transferred to adult care.

Texting Identities: Lessons for Classrooms from Multiethnic Youth Space

ERIC Educational Resources Information Center

Paris, Django

2010-01-01

Paris examines texts worn on objects (like clothing or backpacks), delivered over electronic media, and rapped by youth emcees at a multiethnic high school. He argues that these are identity texts, used by young people to express ethnic and linguistic differences. (Contains 2 figures and 7 notes.)

Intravenous immunoglobulin therapy and systemic lupus erythematosus.

PubMed

Zandman-Goddard, Gisele; Levy, Yair; Shoenfeld, Yehuda

2005-12-01

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. We suggest that intravenous immunoglobulin (IVIg) therapy may be beneficial and safe for various manifestations in SLE. A structured literature search of articles published on the efficacy of IVIg in the treatment of SLE between 1983 and 2005 was conducted. We searched the terms "IVIg," "intravenous immunoglobulin," "lupus," "SLE," and "systemic lupus erythematosus." The various clinical manifestations of SLE that were reported to be successfully treated by IVIg in case reports include autoimmune hemolytic anemia, acquired factor VIII inhibitors, acquired von Willebrand disease, pure red cell aplasia, thrombocytopenia, pancytopenia, myelofibrosis, pneumonitis, pleural effusion, pericarditis, myocarditis, cardiogenic shock, nephritis, end-stage renal disease, encephalitis, neuropsychiatric lupus, psychosis, peripheral neuropathy, polyradiculoneuropathy, and vasculitis. The most extensive experience is with lupus nephritis. There are only a few case series of IVIg use in patients with SLE with various manifestations, in which the response rate to IVIg therapy ranged from 33 to 100%. We suggest that IVIg devoid of sucrose, at a dose of 2 g/kg over a 5-d period given uniformly and at a slow infusion rate in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for cases of SLE that are resistant to or refuse conventional treatment. The duration of therapy is yet to be established. Controlled trials are warranted.

Juvenile systemic lupus erythematosus: onset patterns and short-term outcome in Egyptian children, a single-center experience.

PubMed

Abdel-Hafez, M A; Abdel-Nabi, H

2015-11-01

The objective of this article is to define disease onset pattern and understand the response to therapy in children with systemic lupus erythematosus (SLE) in Egypt. A prospective cohort of 41 Egyptian children diagnosed with SLE was analyzed. SLE Disease Activity Index (SLEDAI) score was used to record disease activity at onset, and renal biopsy was performed to define the stage of lupus nephritis. Response to therapy over a follow-up period ranging from 10 to 50 months was evaluated. The mean age at diagnosis was 12.12 ± 3.45 years. Thirty-six (87.8%) patients were females. Most patients had multiple manifestations at onset. The most common presenting symptoms were pallor and fever (51.2% and 43.9%, respectively). Lupus nephritis was found in 27 (65.9%) children. International Society of Nephrology (ISN) classes I and III were the most common findings on renal biopsy. Neuropsychiatric manifestations were present at disease onset in 19 patients (46.3%) with a bad prognostic course. At diagnosis, high SLEDAI scores were recorded (mean: 29.95 ± 2.06). The mean renal SLEDAI score was 10.2 ± 4. At follow-up 16 (39.02%) patients were in complete remission, 10 (24.39%) were in partial remission, two (4.87%) had active disease, five (12.9%) had relapsed, four (9.75%) had died and four (9.75%) patients were lost to follow-up. Egyptian children with SLE appear to have severe disease on presentation with high SLEDAI scores and high prevalence of lupus nephritis, but respond well to therapy with a favorable short-term prognosis. © The Author(s) 2015.

Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

PubMed

Sato, J O; Corrente, J E; Saad-Magalhães, C

2016-11-01

Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( r s  > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

Outcome of childhood lupus nephritis in Saudi children.

PubMed

Al-Mayouf, Sulaiman Mohammed; AlAmeer, Ali; Alfattani, Areej; Alsonbul, Abdullah

2017-01-01

Our aim in this study is to report the long-term renal outcome of a cohort of Saudi children with systemic lupus erythematosus (SLE). All patients with childhood lupus nephritis (cLN) proved by renal biopsy seen between January 2000 and June 2015 were reviewed. The renal outcome was assessed according to serum creatinine level, protein/creatinine ratio at the last follow-up visit, and/or evidence of renal impairment during follow-up period and end-stage renal disease (ESRD). Additional outcome measures include accrual damage measured by pediatric adaptation of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (pSDI), and death related to SLE was determined. A total of 84 (72 females) cLN patients with follow-up duration of 9.3 years (±5.2) were included in this study. The mean current age was 19.4 years (±5.5) and mean age at onset was 9.2 years (±2.4). The most frequent histopathological class was proliferative glomerulonephritis (64.3%) followed by membranous nephritis (27.4%). The mean activity and chronicity indices were 5.9 (±3.9) and 2.9 (±2.2), respectively. Renal microthrombosis was found in 9 (10.7%) patients. All patients treated with immunosuppressive medications; cyclophosphamide used in 64 followed by mycophenolate mofetil in 42, then azathioprine in 19 patients, while rituximab used in 24 patients. At the last follow-up visit, the mean serum creatinine was 147 umol/L (±197) and the mean protein/ creatinine ratio was 0.8 (± 1.1) while the mean total pSDI was 1.9 (±1.9) and mean renal SDI was 0.7 (±1.1). Sixteen (19%) patients had ESRD and eight of them had class IV nephritis. However, there was no significant difference in ESRD by histological class. The overall survival rates were five years: 94% and 10 years: 87%. Infection was the leading cause of mortality. Our patients had severe cLN and required intensive treatment. Despite the survival rate is comparable to other studies, ESRD is more

Novel Therapeutic Target for the Treatment of Lupus

DTIC Science & Technology

2013-08-01

RhoB, animal model, antibody secretion, antibody therapy, Systemic lupus erythematosus , autoantibodies. 16. SECURITY CLASSIFICATION OF: 17...6 References………………………………………………………………………………..6 Appendices………………………………………………………………………………..N/A 4 INTRODUCTION: Systemic lupus ...Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop, Ph.D. Laura Mandik-Nayak, Ph.D

Brief Report: The Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti-Müllerian Hormone.

PubMed

Tamirou, Farah; Husson, Séverine Nieuwland; Gruson, Damien; Debiève, Frédéric; Lauwerys, Bernard R; Houssiau, Frédéric A

2017-06-01

The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant. © 2017, American College of Rheumatology.

Ethnicity and mortality from systemic lupus erythematosus in the US.

PubMed

Krishnan, E; Hubert, H B

2006-11-01

To study ethnic differences in mortality from systemic lupus erythematosus (lupus) in two large, population-based datasets. We analysed the national death data (1979-98) from the National Center for Health Statistics (Hyattsville, Maryland, USA) and hospitalisation data (1993-2002) from the Nationwide Inpatient Sample (NIS), the largest hospitalisation database in the US. The overall, unadjusted, lupus mortality in the National Center for Health Statistics data was 4.6 per million, whereas the proportion of in-hospital mortality from the NIS was 2.9%. African-Americans had disproportionately higher mortality risk than Caucasians (all-cause mortality relative risk adjusted for age = 1.24 (women), 1.36 (men); lupus mortality relative risk = 3.91 (women), 2.40 (men)). Excess risk was found among in-hospital deaths (odds ratio adjusted for age = 1.4 (women), 1.3 (men)). Lupus death rates increased overall from 1979 to 98 (p<0.001). The proportional increase was greatest among African-Americans. Among Caucasian men, death rates declined significantly (p<0.001), but rates did not change substantially for African-American men. The African-American:Caucasian mortality ratio rose with time among men, but there was little change among women. In analyses of the NIS data adjusted for age, the in-hospital mortality risk decreased with time among Caucasian women (p<0.001). African-Americans with lupus have 2-3-fold higher lupus mortality risk than Caucasians. The magnitude of the risk disparity is disproportionately higher than the disparity in all-cause mortality. A lupus-specific biological factor, as opposed to socioeconomic and access-to-care factors, may be responsible for this phenomenon.

SEMIPARAMETRIC ZERO-INFLATED MODELING IN MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS (MESA)

PubMed Central

Liu, Hai; Ma, Shuangge; Kronmal, Richard; Chan, Kung-Sik

2013-01-01

We analyze the Agatston score of coronary artery calcium (CAC) from the Multi-Ethnic Study of Atherosclerosis (MESA) using semi-parametric zero-inflated modeling approach, where the observed CAC scores from this cohort consist of high frequency of zeroes and continuously distributed positive values. Both partially constrained and unconstrained models are considered to investigate the underlying biological processes of CAC development from zero to positive, and from small amount to large amount. Different from existing studies, a model selection procedure based on likelihood cross-validation is adopted to identify the optimal model, which is justified by comparative Monte Carlo studies. A shrinkaged version of cubic regression spline is used for model estimation and variable selection simultaneously. When applying the proposed methods to the MESA data analysis, we show that the two biological mechanisms influencing the initiation of CAC and the magnitude of CAC when it is positive are better characterized by an unconstrained zero-inflated normal model. Our results are significantly different from those in published studies, and may provide further insights into the biological mechanisms underlying CAC development in human. This highly flexible statistical framework can be applied to zero-inflated data analyses in other areas. PMID:23805172

Mucormycosis complications in systemic lupus erythematosus.

PubMed

Arce-Salinas, C A; Pérez-Silva, E

2010-07-01

This case involved a 75-year-old woman with systemic lupus erythematosus. Two months previously, she had a flare that was treated successfully by increasing the dosages of prednisone and azathioprine. A sudden onset of ocular pain, diplopia, and loss of vision suggestive of optical neuritis or vascular involvement confused the issue, and rhinocerebral zygomycosis was demonstrated later. We review the presentations of this fungal infection in patients with systemic lupus erythematosus with emphasis on its initial features.

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report.

PubMed

Chou, Kun-Ta; Lee, Yu-Chin; Chen, Chun-Wei; Shih, Jen-Fu; Tung, Su-Mei; Yang, Ya-Ting; Perng, Reury-Perng

2007-11-01

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.

Renal transplantation in systemic lupus erythematosus: outcome and prognostic factors in 50 cases from a single centre.

PubMed

Cairoli, Ernesto; Sanchez-Marcos, Carolina; Espinosa, Gerard; Glucksmann, Constanza; Ercilla, Guadalupe; Oppenheimer, Federico; Cervera, Ricard

2014-01-01

End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.

Renal Transplantation in Systemic Lupus Erythematosus: Outcome and Prognostic Factors in 50 Cases from a Single Centre

PubMed Central

Cairoli, Ernesto; Sanchez-Marcos, Carolina; Espinosa, Gerard; Glucksmann, Constanza; Ercilla, Guadalupe; Oppenheimer, Federico; Cervera, Ricard

2014-01-01

Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n = 12), acute rejection (n = 2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P = 0.007) and positive anti-HCV antibodies (P = 0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure. PMID:25013800

Unusual presentation of childhood Systemic Lupus Erythematosus

PubMed Central

Kumar, Sathish; Agarwal, Indira

2007-01-01

Bullous systemic lupus erythematosus is a rare blistering condition with a distinctive combination of clinical, histological and immunopathologic features that together constitute a unique bullous disease phenotype. It is often associated with autoimmunity to type VII collagen. Here we report a child who presented with bullous systemic lupus erythematosus. Rapid resolution of the blisters occurred following treatment with dapsone. PMID:18028550

Issues and advances in the management and pathogenesis of cutaneous lupus erythematosus.

PubMed

Pelle, Michelle T

2006-01-01

Evidence-based therapy for cutaneous lupus is lacking. A new clinical assessment tool for cutaneous lupus, the CLASI score, will enable more standardized assessments of response to therapy. Anti-Ro autoantibodies are associated with photosensitive SLE and SCLE, and they play a role in cell survival following ultraviolet exposure. Ro also functions in quality control of small RNAs, important in the prevention of autoimmune disease. Drug-induced lupus erythematosus can be anti-Ro- or anti-dsDNA-associated; SCLE and photosensitivity are characteristic of Ro-positive drug-induced lupus. Biologic therapies and IVIg are being studied for the treatment of SLE and cutaneous lupus. Large, controlled trials are needed, not only to evaluate newer therapies, but also to substantiate and define the usage of traditional therapies for cutaneous lupus erythematosus.

Biomarkers for CNS involvement in pediatric lupus

PubMed Central

Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

2015-01-01

CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

21 CFR 866.5820 - Systemic lupus erythema-tosus immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Systemic lupus erythema-tosus immunological test... Systems § 866.5820 Systemic lupus erythema-tosus immunological test system. (a) Identification. A systemic lupus erythematosus (SLE) immunological test system is a device that consists of the reagents used to...

High prolactin levels are independently associated with damage accrual in systemic lupus erythematosus patients.

PubMed

Ugarte-Gil, M F; Gamboa-Cárdenas, R V; Zevallos, F; Medina, M; Cucho-Venegas, J M; Perich-Campos, R A; Alfaro-Lozano, J L; Rodriguez-Bellido, Z; Alarcón, G S; Pastor-Asurza, C A

2014-09-01

to determine whether prolactin levels are independently associated with disease damage in systemic lupus erythematosus (SLE) patients. these cross-sectional analyses were conducted in SLE patient members of the Almenara Lupus Cohort who were seen between January 2012 and June 2013. Disease damage was ascertained with the System Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). Prolactin was measured in ng/ml. The association between prolactin levels and the SDI (total and its domains) was evaluated using Spearman's correlation. Subsequently, adjusted Poisson regression models were performed to evaluate these associations. 160 patients were included. 147 (91.9%) were female; their median age at diagnosis was 33.4 (interquartile range (IQR): 26.0-44.3) years; their disease duration was 5.5 (IQR: 2.6-9.7) years. The median prolactin value was 16.8 (IQR: 11.8-24.5) ng/ml. After adjusting for confounders in the Poisson regression model the estimated rate ratios (RR) and 95% confidence interval (CI) for each 10 ng/ml increment of prolactin were 1.13 (95% CI 1.60-1.20, p<0.001) for the total SDI score, 1.15 (1.03-1.28, p=0.003) for the renal domain and 1.41 (1.11-1.79, p=0.003) for the cardiac/peripheral vascular domains. there was a positive association between prolactin levels and the SDI (overall and its renal and cardiac/peripheral vascular domains), independently of other well-known risk factors. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Annotated Bibliography of Multi-Ethnic Curriculum Materials, Sixth Supplement.

ERIC Educational Resources Information Center

Midwest Center for Equal Educational Opportunity, Columbia, MO.

This annotated bibliography cites 132 multiethnic curriculum materials for grades K through 12. It is designed to be used by students, teachers, and administrators. Some of the materials focus on specific groups, such as Blacks, American Indians, Puerto Ricans, Italian Americans, Chinese Americans, Slavs, Scandinavians, and women. Other materials…

Land use, residential density, and walking. The multi-ethnic study of atherosclerosis.

PubMed

Rodríguez, Daniel A; Evenson, Kelly R; Diez Roux, Ana V; Brines, Shannon J

2009-11-01

The neighborhood environment may play a role in encouraging sedentary patterns, especially for middle-aged and older adults. The aim of this study was to examine the associations between walking and neighborhood population density, retail availability, and land-use distribution using data from a cohort of adults aged 45 to 84 years. Data from a multi-ethnic sample of 5529 adult residents of Baltimore MD, Chicago IL, Forsyth County NC, Los Angeles CA, New York NY, and St. Paul MN enrolled in the Multi-Ethnic Study of Atherosclerosis in 2000-2002 were linked to secondary land-use and population data. Participant reports of access to destinations and stores and objective measures of the percentage of land area in parcels devoted to retail land uses, the population divided by land area in parcels, and the mixture of uses for areas within 200 m of each participant's residence were examined. Multinomial logistic regression was used to investigate associations of self-reported and objective neighborhood characteristics with walking. All analyses were conducted in 2008 and 2009. After adjustment for individual-level characteristics and neighborhood connectivity, it was found that higher density, greater land area devoted to retail uses, and self-reported proximity of destinations and ease of walking to places were each related to walking. In models including all land-use measures, population density was positively associated with walking to places and with walking for exercise for more than 90 minutes/week, both relative to no walking. Availability of retail was associated with walking to places relative to not walking, and having a more proportional mix of land uses was associated with walking for exercise for more than 90 minutes/week, while self-reported ease of access to places was related to higher levels of exercise walking, both relative to not walking. Residential density and the presence of retail uses are related to various walking behaviors. Efforts to increase

Acquired activated protein C resistance is associated with lupus anticoagulants and thrombotic events in pediatric patients with systemic lupus erythematosus.

PubMed

Male, C; Mitchell, L; Julian, J; Vegh, P; Joshua, P; Adams, M; David, M; Andrew, M E

2001-02-15

Acquired activated protein C resistance (APCR) has been hypothesized as a possible mechanism by which antiphospholipid antibodies (APLAs) cause thrombotic events (TEs). However, available evidence for an association of acquired APCR with APLAs is limited. More importantly, an association of acquired APCR with TEs has not been demonstrated. The objective of the study was to determine, in pediatric patients with systemic lupus erythematosus (SLE), whether (1) acquired APCR is associated with the presence of APLAs, (2) APCR is associated with TEs, and (3) there is an interaction between APCR and APLAs in association with TEs. A cross-sectional cohort study of 59 consecutive, nonselected children with SLE was conducted. Primary clinical outcomes were symptomatic TEs, confirmed by objective radiographic tests. Laboratory testing included lupus anticoagulants (LAs), anticardiolipin antibodies (ACLAs), APC ratio, protein S, protein C, and factor V Leiden. The results revealed that TEs occurred in 10 (17%) of 59 patients. Acquired APCR was present in 18 (31%) of 58 patients. Acquired APCR was significantly associated with the presence of LAs but not ACLAs. Acquired APCR was also significantly associated with TEs. There was significant interaction between APCR and LAs in the association with TEs. Presence of both APCR and LAs was associated with the highest risk of a TE. Protein S and protein C concentrations were not associated with the presence of APLAs, APCR, or TEs. Presence of acquired APCR is a marker identifying LA-positive patients at high risk of TEs. Acquired APCR may reflect interference of LAs with the protein C pathway that may represent a mechanism of LA-associated TEs. (Blood. 2001;97:844-849)

Moving East: the Euro-Lupus Nephritis regimen in Asia.

PubMed

Houssiau, Frédéric A

2016-01-01

Treatment of lupus nephritis is more evidenced-based than ever. Yet many areas of uncertainty persist. The article by Rathi et al. brings a piece to the puzzle by comparing, in a group of Indian patients, the Euro-Lupus low-dose i.v. cyclophosphamide regimen with mycophenolate mofetil. Although some caveats must be raised, the results suggest that, after crossing the Atlantic, the Euro-Lupus regimen may well be moving East. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Clinical characteristics and laboratory findings of 252 Chinese patients with anti-phospholipid syndrome: comparison with Euro-Phospholipid cohort.

PubMed

Shi, Hui; Teng, Jia-Lin; Sun, Yue; Wu, Xin-Yao; Hu, Qiong-Yi; Liu, Hong-Lei; Cheng, Xiao-Bing; Yin, Yu-Feng; Ye, Jun-Na; Chen, Pojen P; Yang, Cheng-de

2017-03-01

This study aims to characterize the Chinese Han patients with anti-phospholipid syndrome (APS) and compare the data with those of the Euro-Phospholipid cohort. We conducted a single center study consisting of 252 patients with definite APS from 2000 to 2015. We analyzed the clinical and laboratory characteristics of our cohort and compared the data with those of the Euro-Phospholipid cohort. Our cohort consisted of 216 females and 36 males, with a mean age at entry into this study of 41 years (range 11-74 years). Of these patients, 69 (27.4%) patients had primary APS, and 183 (72.6%) had secondary APS (SAPS), including 163 (64.7%) patients had systemic lupus erythematosus (SLE). Thrombotic events occurred in 190 (75.4%) patients, and the most common ones were deep vein thrombosis (40.1%) and stroke (23.8%), which were similar to the reports of the Euro-Phospholipid cohort. In contrast, our cohort had less pulmonary embolism (6.7%). Among 93 females with 299 pregnancy episodes, the rates of early (<10 weeks) and late fetal loss (≥10 weeks) were, respectively, 37.8% and 24.4%. The latter was significantly higher than that of the Euro-Phospholipid cohort. Moreover, 7 APS nephropathy patients (characterized histopathologically by thrombotic microangiopathy) and 8 catastrophic APS patients were found in our cohort. Anti-cardiolipin antibodies (aCL) were detected in 169 (67.1%) patients, lupus anti-coagulant (LA) was detected in 83 (32.9%), and anti-β2 glycoprotein I antibodies (anti-β2GPI) in 148 (58.7%) patients. These results show that some clinical manifestations of APS may vary among different racial groups.

Association between ulcerative colitis and systemic lupus erythematosus: report of two cases.

PubMed

Koutroubakis, I E; Kritikos, H; Mouzas, I A; Spanoudakis, S M; Kapsoritakis, A N; Petinaki, E; Kouroumalis, E A; Manousos, O N

1998-05-01

Common aetiopathogenic factors may explain the association of ulcerative colitis with autoimmune disorders such as systemic lupus erythematosus. We report two cases of ulcerative colitis associated with idiopathic systemic lupus erythematosus: one patient who developed ulcerative colitis 11 years after having been diagnosed as a case of systemic lupus erythematosus and one case of simultaneous appearance of the two diseases. The lupus clinical manifestations were in neither case correlated with the treatment of ulcerative colitis. The association between ulcerative colitis and systemic lupus erythematosus is rare. Although a chance occurrence cannot be excluded it is possible that both conditions share some genetic or immunological defects.

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

PubMed Central

Sanchez, Elena; Nadig, Ajay; Richardson, Bruce C; Freedman, Barry I; Kaufman, Kenneth M; Kelly, Jennifer A; Niewold, Timothy B; Kamen, Diane L; Gilkeson, Gary S; Ziegler, Julie T; Langefeld, Carl D; Alarcón, Graciela S; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Brown, Elizabeth E; Kimberly, Robert P; Reveille, John D; Vilá, Luis M; Merrill, Joan T; Anaya, Juan-Manuel; James, Judith A; Pons-Estel, Bernardo A; Martin, Javier; Park, So-Yeon; Bang, So-Young; Bae, Sang-Cheol; Moser, Kathy L; Vyse, Timothy J; Criswell, Lindsey A; Gaffney, Patrick M; Tsao, Betty P; Jacob, Chaim O; Harley, John B; Alarcón-Riquelme, Marta E; Sawalha, Amr H

2011-01-01

Objective Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus. Materials and methods 4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria. Results Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0×10−6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing. Conclusion Significant associations were found between lupus clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future. PMID:21719445

A multi-group confirmatory factor analyses of the LupusPRO between southern California and Filipino samples of patients with systemic lupus erythematosus.

PubMed

Azizoddin, D R; Olmstead, R; Cost, C; Jolly, M; Ayeroff, J; Racaza, G; Sumner, L A; Ormseth, S; Weisman, M; Nicassio, P M

2017-08-01

Introduction Systemic lupus erythematosus (SLE) leads to a range of biopsychosocial health outcomes through an unpredictable and complex disease path. The LupusPRO is a comprehensive, self-report measure developed specifically for populations with SLE, which assesses both health-related quality of life and non-health related quality of life. Given its increasingly widespread use, additional research is needed to evaluate the psychometric integrity of the LupusPRO across diverse populations. The objectives of this study were to evaluate the performance of the LupusPRO in two divergent patient samples and the model fit between both samples. Methods Two diverse samples with SLE included 136 patients from an ethnically-diverse, urban region in southern California and 100 from an ethnically-homogenous, rural region in Manila, Philippines. All patients met the ACR classification criteria for SLE. Confirmatory factor analysis (CFAs) were conducted in each sample separately and combined to provide evidence of the factorial integrity of the 12 subscales in the LupusPRO. Results Demographic analyses indicated significant differences in age, disease activity and duration, education, income, insurance, and medication use between groups. Results of the separate CFAs indicated moderate fit to the data for the hypothesized 12-factor model for both the Manila and southern California groups, respectively [χ 2 (794) = 1283.32, p < 0.001, Comparative Fit Index (CFI) = 0.793; χ 2 (794) =1398.44, p < 0.001, CFI = 0.858]. When the factor structures of the LupusPRO in the southern California and Manila groups were constrained to be equal between the two groups, findings revealed that the factor structures of measured variables fit the two groups reasonably well [χ 2  (1697) = 2950.413, df = 1697, p < 0.000; CFI = 0.811]. After removing seven constraints and eight correlations suggested by the Lagrange multiplier test, the model fit improved

Validation of an Argentine version of Lupus Quality of Life questionnaire.

PubMed

Machado Escobar, M A; Yacuzzi, M S; Martinez, R N; González Lucero, L; Bellomio, V I; Santana, M; Galindo, L; Mayer, M M; Barreira, J C; Sarano, J; Gomez, G; Collado, M V; Martinez, A; Orozco, M C; Betancur, G; Dal Pra, F; Sanchez, A; Juarez, V; Lucero, E V

2016-12-01

To determine reproducibility and validity of an Argentine version of the Lupus Quality of Life questionnaire (LupusQoL) and to determine cut-off values in the questionnaire. One hundred and forty-seven systemic lupus erythematosus patients (American College of Rheumatology 1982/1997) were assessed from April 2014 to July 2014. Demographic and socioeconomic variables were collected, as well as SELENA/SLEDAI, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index Score, comorbidities and treatment data. Patients completed LupusQoL-Argentine version and European Quality of Life Questionnaire (EuroQoL-5D). Internal consistency and reliability were examined. Convergent validity with EuroQoL-5D was assessed through analysis of latent classes, which established homogeneous categories from the responses of each domain of LupusQoL and for the total. Out of 147 patients, 93.2% were female, mean age 36.4 ± 11.1 years, mean disease duration 2.7 ± 9 years, mean SELENA/SLEDAI 2.7 ± 3 points. The cut-off point that defined good or bad quality of life was 0.739 for EuroQoL 5D and 63 for LupusQoL. Cut-off values for each LupusQoL domain were also defined, creating two classes in each of them. There was moderate to high concordance to classify quality of life (Kappa = 0.74, 95% confidence interval = 0.54, 0.95). The Argentine version of LupusQoL is a valid, reliable and reproducible instrument to assess quality of life. In this study, cut-off points that allow the classification of patients regarding whether they have good or bad quality of life are established for the first time. © The Author(s) 2016.

Functional Connectivity Changes in Systemic Lupus Erythematosus: A Resting-State Study.

PubMed

Nystedt, Jessika; Mannfolk, Peter; Jönsen, Andreas; Bengtsson, Anders; Nilsson, Petra; Sundgren, Pia C; Strandberg, Tor O

2018-05-01

To investigate resting-state functional connectivity of lupus patients and associated subgroups according to the ACR NPSLE case definitions (ACR ad hoc). In addition, we investigated whether or not the observed alterations correlated with disease duration, the systemic lupus erythematosus (SLE)-Disease Activity Index-2000 (SLEDAI-2k), and Systemic Lupus International Collaborating Clinical/ACR organ damage index (SDI)-scores. Anatomical 3T magnetic resonance imaging (MRI) and resting-state functional MRI were performed in 61 female lupus patients (mean age = 37.0 years, range = 18.2-52.0 years) and 20 gender- and age-matched controls (mean age = 36.2 years, range = 23.3-52.2 years) in conjunction with clinical examination and laboratory testing. Whole-brain voxelwise functional connectivity analysis with permutation testing was performed to extract network components that differed in lupus patients relative to healthy controls (HCs). Lupus patients exhibited both inter- and intranetwork hypo- and hyperconnectivity involving several crucial networks. We found reduced connectivity within the default mode network (DMN), the central executive network (CEN), and in-between the DMN and CEN in lupus patients. Increased connectivity was primarily observed within and between the sensory motor network in lupus patients when compared to HCs. Comparing lupus patients with and without neuropsychiatric symptoms, hypoconnectivity was more pronounced in the group with neuropsychiatric complaints. The functional connectivity of SLE patients was both positively and negatively correlated to duration of disease. We conclude that SLE patients in general and neuropsychiatric SLE patients in particular experience altered brain connectivity. These patterns may be due both to direct neuronal damage and compensatory mechanisms through neuronal rewiring and recruitment and may partly explain neuropsychiatric symptoms in SLE patients.

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus.

PubMed

Sjöwall, C; Zapf, J; von Löhneysen, S; Magorivska, I; Biermann, M; Janko, C; Winkler, S; Bilyy, R; Schett, G; Herrmann, M; Muñoz, L E

2015-05-01

In addition to the redundancy of the receptors for the Fc portion of immunoglobulins, glycans result in potential ligands for a plethora of lectin receptors found in immune effector cells. Here we analysed the exposure of glycans containing fucosyl residues and the fucosylated tri-mannose N-type core by complexed native IgG in longitudinal serum samples of well-characterized patients with systemic lupus erythematosus. Consecutive serum samples of a cohort of 15 patients with systemic lupus erythematosus during periods of increased disease activity and remission were analysed. All patients fulfilled the 1982 American College of Rheumatology classification criteria. Sera of 15 sex- and age-matched normal healthy blood donors served as controls. The levels and type of glycosylation of complexed random IgG was measured with lectin enzyme-immunosorbent assays. After specifically gathering IgG complexes from sera, biotinylated lectins Aleuria aurantia lectin and Lens culinaris agglutinin were employed to detect IgG-associated fucosyl residues and the fucosylated tri-mannose N-glycan core, respectively. In sandwich-ELISAs, IgG-associated IgM, IgA, C1q, C3c and C-reactive protein (CRP) were detected as candidates for IgG immune complex constituents. We studied associations of the glycan of complexed IgG and disease activity according to the physician's global assessment of disease activity and the systemic lupus erythematosus disease activity index 2000 documented at the moment of blood taking. Our results showed significantly higher levels of Aleuria aurantia lectin and Lens culinaris agglutinin binding sites exposed on IgG complexes of patients with systemic lupus erythematosus than on those of normal healthy blood donors. Disease activity in systemic lupus erythematosus correlated with higher exposure of Aleuria aurantia lectin-reactive fucosyl residues by immobilized IgG complexes. Top levels of Aleuria aurantia lectin-reactivity were found in samples taken during the

Biomarkers in systemic lupus erythematosus: challenges and prospects for the future

PubMed Central

Kao, Amy H.; Manzi, Susan; Ahearn, Joseph M.

2013-01-01

The search for lupus biomarkers to diagnose, monitor, stratify, and predict individual response to therapy is currently more intense than ever before. This effort is essential for several reasons. First, epidemic overdiagnosis and underdiagnosis of lupus, even by certified rheumatologists, leads to errors in therapy with concomitant side effects which may be more serious than the disease itself. Second, identification of lupus flares remains as much an art as it is a science. Third, the capacity to stratify patients so as to predict those who will develop specific patterns of organ involvement is not currently possible but would potentially lead to preventive therapeutic strategies. Fourth, only one new drug for the treatment of lupus has been approved by the US Food and Drug Administration in over 50 years. A major obstacle in this pipeline is the dearth of biomarkers available to prove a patient has responded to an experimental therapeutic intervention. This review will summarize the challenges faced in the discovery and validation of lupus biomarkers, the most promising lupus biomarkers identified to date, and the promise of future directions. PMID:23904865

Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management.

PubMed

Lam, Nguyet-Cam Vu; Ghetu, Maria V; Bieniek, Marzena L

2016-08-15

Systemic lupus erythematosus is an autoimmune disease that affects many systems, including the skin, musculoskeletal, renal, neuropsychiatric, hematologic, cardiovascular, pulmonary, and reproductive systems. Family physicians should be familiar with the manifestations of lupus to aid in early diagnosis, monitoring patients with mild disease, recognizing warning signs that require referral to a rheumatologist, and helping to monitor disease activity and treatment in patients with moderate to severe disease. The American College of Rheumatology has 11 classification criteria for lupus. If a patient meets at least four criteria, lupus can be diagnosed with 95% specificity and 85% sensitivity. All patients with lupus should receive education, counseling, and support. Hydroxychloroquine is the cornerstone of treatment because it reduces disease flares and other constitutional symptoms. Low-dose glucocorticoids can be used to treat most manifestations of lupus. The use of immunosuppressive and cytotoxic agents depends on the body systems affected. Patients with mild disease that does not involve major organ systems can be monitored by their family physician. Patients with increased disease activity, complications, or adverse effects from treatment should be referred to a rheumatologist. To optimize treatment, it is important that a rheumatologist coordinate closely with the patient's family physician to improve chronic care as well as preventive health services.

Evidence for gene-gene epistatic interactions among susceptibility loci for systemic lupus erythematosus.

PubMed

Hughes, Travis; Adler, Adam; Kelly, Jennifer A; Kaufman, Kenneth M; Williams, Adrienne H; Langefeld, Carl D; Brown, Elizabeth E; Alarcón, Graciela S; Kimberly, Robert P; Edberg, Jeffrey C; Ramsey-Goldman, Rosalind; Petri, Michelle; Boackle, Susan A; Stevens, Anne M; Reveille, John D; Sanchez, Elena; Martín, Javier; Niewold, Timothy B; Vilá, Luis M; Scofield, R Hal; Gilkeson, Gary S; Gaffney, Patrick M; Criswell, Lindsey A; Moser, Kathy L; Merrill, Joan T; Jacob, Chaim O; Tsao, Betty P; James, Judith A; Vyse, Timothy J; Alarcón-Riquelme, Marta E; Harley, John B; Richardson, Bruce C; Sawalha, Amr H

2012-02-01

Several confirmed genetic susceptibility loci for lupus have been described. To date, no clear evidence for genetic epistasis in lupus has been established. The aim of this study was to test for gene-gene interactions in a number of known lupus susceptibility loci. Eighteen single-nucleotide polymorphisms tagging independent and confirmed lupus susceptibility loci were genotyped in a set of 4,248 patients with lupus and 3,818 normal healthy control subjects of European descent. Epistasis was tested by a 2-step approach using both parametric and nonparametric methods. The false discovery rate (FDR) method was used to correct for multiple testing. We detected and confirmed gene-gene interactions between the HLA region and CTLA4, IRF5, and ITGAM and between PDCD1 and IL21 in patients with lupus. The most significant interaction detected by parametric analysis was between rs3131379 in the HLA region and rs231775 in CTLA4 (interaction odds ratio 1.19, Z = 3.95, P = 7.8 × 10(-5) [FDR ≤0.05], P for multifactor dimensionality reduction = 5.9 × 10(-45)). Importantly, our data suggest that in patients with lupus, the presence of the HLA lupus risk alleles in rs1270942 and rs3131379 increases the odds of also carrying the lupus risk allele in IRF5 (rs2070197) by 17% and 16%, respectively (P = 0.0028 and P = 0.0047, respectively). We provide evidence for gene-gene epistasis in systemic lupus erythematosus. These findings support a role for genetic interaction contributing to the complexity of lupus heritability. Copyright © 2012 by the American College of Rheumatology.

Racial and Ethnic Disparities in the Pregnancies of Women With Systemic Lupus Erythematosus.

PubMed

Clowse, Megan E B; Grotegut, Chad

2016-10-01

Both systemic lupus erythematosus (SLE; lupus) and pregnancy individually have significant racial disparities, with black women experiencing higher rates of complications, yet no large studies have focused on the impact of race/ethnicity on pregnancy outcomes among women with lupus. Using the Nationwide Inpatient Sample (NIS) for 2008-2010, pregnancy delivery discharges were identified and pregnancy outcomes were compared for women with lupus by maternal race/ethnicity. Adjusted odds ratios were used to compare pregnancy outcomes between black and white or Hispanic and white women with lupus. In this period, the NIS included 13,553 deliveries with lupus and 12,510,565 deliveries without lupus. Compared to white women with lupus, black and Hispanic women had higher rates of chronic hypertension, chronic renal failure, pneumonia, and acute renal failure. There was a high degree of pregnancy complication in all women with lupus, but especially in black and Hispanic women, with more than 40% cesarean-section delivery; preterm labor in 14.3% of white, 24.7% of black (odds ratio [OR] 1.97), and 20.6% of Hispanic (OR 1.56) deliveries; and preeclampsia and gestational hypertension in almost 20% of black and Hispanic pregnancies. After adjustment for predictors of pregnancy outcomes and racial differences in nonlupus pregnancy, black and Hispanic women with lupus had higher than expected rates of preeclampsia, preterm labor, and fetal growth restriction. Black and Hispanic women with lupus have disproportionately poor pregnancy outcomes. This study suggests that identifying the key causes of these differences and targeting interventions to the women of greatest need is an essential next step. © 2016, American College of Rheumatology.

Recent Advances in the Immunopathogenesis of Systemic Lupus Erythematosus

PubMed Central

Bardana, Emil J.; Pirofsky, Bernard

1975-01-01

Systemic lupus erythematosus (SLE) is a chronic multisystem inflammatory disease having definite etiologic associations with ethnic, genetic, viral and immunologic factors. Its pathologic hallmark, vasculitis, is currently felt to be the end result of an immune-complex mechanism. Several clinical and serologic variants of SLE are recognized including discoid lupus erythematosus (DLE), mixed connective tissue disease (MCTD) and drug-induced equivalents—such as procainamide-induced lupus (PIL). The distinguishing features of these variants as well as their prognosis and therapy are discussed in relation to recent developments in the immunopathogenesis of SLE. PMID:46657

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

PubMed

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

PubMed Central

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P. J.

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials. PMID:29928273

Intranuclear delivery of the transcription modulation domain of Tbet-improved lupus nephritis in (NZB/NZW) F1 lupus-prone mice.

PubMed

Moon, Jae-Seung; Mun, Chin Hee; Kim, Jung-Ho; Cho, Jen-Young; Park, Sung-Dong; Park, Tae-Yoon; Shin, Jin-Su; Ho, Chun-Chang; Park, Yong-Beom; Ghosh, Sankar; Bothwell, Alfred L M; Lee, Sang-Won; Lee, Sang-Kyou

2018-05-01

Excessive expression of Tbet and IFNγ is evidence of systemic lupus erythematosus (SLE) in lupus patients. In this study, the nucleus-transducible form of Transcription Modulation Domain (TMD) of Tbet (ntTbet-TMD), which is a fusion protein between Protein Transduction Domain Hph-1 (Hph-1-PTD) and the TMD of Tbet comprising DNA binding domain and isotype-specific domain, was generated to inhibit Tbet-mediated transcription in the interactomic manner. ntTbet-TMD was effectively delivered into the nucleus of the cells and specifically inhibited Tbet-mediated transcription without influencing the differentiation of other T cell subsets and signaling events for T cell activation. The severity of nephritis was significantly reduced by ntTbet-TMD as effectively as methylprednisolone in lupus-prone mice. The number of Th1, Th2 or Th17 cells and the secretion of their cytokines substantially decreased in the spleen and kidney of lupus-prone mice by ntTbet-TMD treatment. In contrast to methylprednisolone, the marked increase of Treg cells and the secretion of their immunosuppressive cytokine were detected in the spleen of (NZB/NZW) F1 mice treated with ntTbet-TMD. Thus, ntTbet-TMD can improve nephritis in lupus-prone mice by modulating the overall proinflammatory microenvironment and rebalancing T cell subsets, leading to new immune therapeutics for Th1-mediated autoimmune diseases. Copyright © 2017 International Society of Nephrology. All rights reserved.

What Black Women Should Know about Lupus: Ideas for Community Programs.

ERIC Educational Resources Information Center

National Inst. of Arthritis and Musculoskeletal and Skin Diseases (NIH), Bethesda, MD.

Lupus is a serious health problem that mainly affects young women between the ages of 15 and 44. Although people of all races may get lupus, black women have three times higher rates of incidence, prevalence, and mortality than white women. With early detection and proper treatment, most people with lupus can lead a normal life. This kit is…

Infections and systemic lupus erythematosus

PubMed Central

Skare, Thelma Larocca; Dagostini, Jéssica Scherer; Zanardi, Patricia Imai; Nisihara, Renato Mitsunori

2016-01-01

ABSTRACT Objective To determine the incidence of infections in a population of systemic lupus erythematosus individuals and the characteristics of infections regarding original site, as well as to study the possible associations between infections and treatment. Methods An analytical retrospective study using data from medical charts of systemic lupus erythematosus patients from a single university hospital. A total of 144 patients followed up for five years were included. Data collected comprised age of patients and age at onset of lupus, sex and ethnicity, disease duration before the study period, medications, cumulative dose of prednisone, occurrence of infections and their original site. Results The most frequent infections were urinary tract infections (correlated to use of prednisone − p<0.0001 and cyclophosphamide − p=0.045), upper airways infections (correlated to use of prednisone − p=0.0004, mycophenolate mofetil − p=0.0005, and cyclosporine − p=0.025), and pneumonia (associated to prednisone − p=0.017). Conclusion Prednisone was the drug more often associated with presence of infections, pointing to the need for a more judicious management of this drug. PMID:27074234

The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus: an observational longitudinal study.

PubMed

Compagno, Michele; Gullstrand, Birgitta; Jacobsen, Søren; Eilertsen, Gro Ø; Nilsson, Jan Åke; Lood, Christian; Jönsen, Andreas; Truedsson, Lennart; Sturfelt, Gunnar; Bengtsson, Anders A

2016-02-10

Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry-based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. In this study, we aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). The diagnostic accuracy for SLE diagnosis of the PNC assay was studied by cross-sectional assessment of blood samples from 148 healthy control subjects and a multicenter rheumatic group (MRG) of 529 patients with different rheumatic symptoms. A cohort of 69 patients with an established SLE diagnosis (SLE cohort) underwent longitudinal clinical and laboratory follow-up for analysis of the temporal relationships between PNC positivity and specific clinical manifestations. In 35 of 529 MRG patients, 13 of whom had SLE, the PNC assay result was positive. Combined positivity of the PNC assay and anti-double-stranded DNA antibodies increased specificity and positive predictive value for SLE diagnosis to 0.99 and 0.67, respectively. In the longitudinal study, 42 of 69 SLE cohort patients had positive results in the PNC assay at least once. PNC assay positivity was associated with current hematological manifestations and could predict mucocutaneous manifestations. When combined with hypocomplementemia, PNC positivity preceded increased Systemic Lupus Erythematosus Disease Activity Index 2000 score, glomerulonephritis, and alopecia. Serum-mediated PNC by polymorphonuclear leukocytes is commonly but not exclusively seen in patients with SLE. The PNC assay may be used in follow-up of patients with SLE and, especially in combination with other routinely assessed laboratory tests, may help to predict flares and different clinical manifestations, including glomerulonephritis. Our results encourage further

Lots of autoantibodies equal lupus?

PubMed Central

2013-01-01

Autoantibodies may be found years before an autoimmune disease becomes clinically apparent. For systemic lupus erythematosus (SLE), those to RNA-binding proteins, to phospholipids, and to double-stranded DNA, in particular, have been found in sera of SLE patients years before the diagnosis was made. New data now show in an unbiased way that, in patients with early SLE, no single antibody class or specificity is associated with progression to SLE. Rather, an increasing number of autoantibody specificities, such as to thyroid antigens, was observed in patients progressing. This points to more generalized B cell autoreactivity during progression to SLE, underlying lupus disease manifestations. PMID:23347779

Lupus mastitis: a mimicker of breast carcinoma

PubMed Central

Warne, Richard Roger; Taylor, Donna; Segal, Amanda; Irish, Ashley

2011-01-01

The authors present a case of lupus mastitis which was initially diagnosed following an incisional biopsy of a breast lump, with similar pathology found 2 years later after an ultrasound guided biopsy of the same lump. The woman had been diagnosed 7 years before with systemic lupus erythematosus. The radiological and pathological features are presented in this report with discussion of similar cases in the literature. PMID:22669997

Effective Self-Management Interventions for Patients With Lupus: Potential Impact of Peer Mentoring.

PubMed

Williams, Edith M; Egede, Leonard; Faith, Trevor; Oates, James

2017-06-01

Systemic lupus erythematosus (SLE) is associated with significant mortality, morbidity and cost for the individual patient and society. In the United States, African Americans (AAs) have 3-4 times greater prevalence of lupus, risk of developing lupus at an earlier age and lupus-related disease activity, organ damage and mortality compared with whites. Evidence-based self-management interventions that incorporate both social support and health education have reduced pain, improved function and delayed disability among patients with lupus. However, AAs and women are still disproportionately affected by lupus. This article presents the argument that peer mentoring may be an especially effective intervention approach for AA women with SLE. SLE peers with a track record of success in lupus management and have a personal perspective that clinicians often lack. This commonality and credibility can establish trust, increase communication and, in turn, decrease disparities in healthcare outcomes. Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

Cutaneous lupus erythematosus of elbows: A distinct entity?

PubMed

Singh, Nidhi; Chandrashekar, Laxmisha; Kumar, Nava; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

2016-01-01

The elbow is not recognized as common site for cutaneous lupus erythematosus (CLE) lesions. Twelve cases of CLE over the elbows were evaluated for systemic involvement and Cutaneous Lupus Disease Area and Severity Index activity and damage scores and Systemic Lupus Erythematosus Disease Activity Index scoring was done. Histopathological examination of the affected skin was performed in doubtful cases. Most of the patients were women (10, 83.3%) with mean age of 28.75 years. Three patients had only elbow lesions and the remaining nine patients had CLE lesions at sites other than the elbows, of which five had elbow lesions preceding skin lesions elsewhere over the body and three patients were not aware of whether elbow lesions preceded or succeeded CLE lesions at other sites, and one patient had noticed malar rash 9 months prior to elbow lesions. All the patients antinuclear antibody positivity, systemic involvement, and fulfilled criteria for systemic lupus erythematosus. This peculiar localization of CLE to the elbows may be associated with a greater risk of systemic involvement and may be an predictor of flare of LE.

Detection of lupus erythematosus cells in pleural effusion: An unusual presentation of systemic lupus erythematosus.

PubMed

Gulhane, Sushma; Gangane, Nitin

2012-01-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease typically diagnosed by a combination of physical findings and clinical laboratory testing. Several decades ago, the diagnosis of lupus included the lupus erythematosus (LE) cell assay. SLE is associated with pleuropulmonary manifestations in well over 50% of cases. Although pleural effusion is common but very rarely is the initial manifestation of disease. There are very few reports of SLE diagnosed in a cytopathology laboratory. We report an unusual case of SLE in a 16-year-old female who presented with acute shortness of breath, fever and cough. Her chest radiograph showed bilateral pleural effusion. This effusion was tapped and sent to the cytopathology laboratory. The cytological examination of the pleural fluid revealed numerous LE cells and led to the diagnosis of SLE. Autoimmune serology techniques such as anti-nuclear antibody staining have replaced the LE cell assay. However, as presented in this report and found in a review of the literature, the in vivo finding of LE cells by cytopathology can provide an important clue to the diagnosis of SLE, especially when associated with an uncommon presentation.

NAFLD prevalence differs among hispanic subgroups: the Multi-Ethnic Study of Atherosclerosis.

PubMed

Fleischman, Michael Wayne; Budoff, Matthew; Zeb, Ifran; Li, Dong; Foster, Temitope

2014-05-07

To compare prevalence rates of non-alcoholic fatty liver disease (NAFLD) between Hispanics of Mexican origin and Hispanics of Dominican and Puerto Rican origin. We evaluated prevalence rates of NAFLD between the two largest sub-populations of Hispanics in the United States; Hispanics of Mexican origin and Hispanics of Caribbean origin (Dominican and Puerto Rican), in the multi-ethnic study of atherosclerosis (MESA) cohort. MESA is a large, population based, multi-center cohort study comprised of 6814 healthy Caucasian, African-American, Hispanic, and Asian men and women aged 45-84. We utilized the baseline serum, anthropometric and radiographic measurements obtained between 2000 and 2002. NAFLD was measured via computed tomography scan and was defined as liver/spleen attenuation ratio < 1. There were 788 Hispanic participants included in the study after exclusions. The prevalence of NAFLD was 29% (n = 225). Hispanics of Mexican origin had a significantly higher prevalence of NAFLD (33%), compared to Hispanics of Dominican origin (16%), (P < 0.01) and Hispanics of Puerto Rican origin (18%), (P < 0.01). After controlling for age, sex, BMI, waist circumference, hypertension, serum HDL, triglyceride and CRP level and insulin resistance, Hispanics of Mexican origin remained significantly more likely to have NAFLD than those of Dominican and Puerto Rican origin. United States Hispanics of Mexican origin have a significantly higher prevalence of NAFLD when compared to United States Hispanics of Dominican or Puerto Rican origin after controlling for known risk factors. Care should be taken when performing risk assessment in Hispanic populations not to make assumptions of homogeneity.

Cutaneous manifestations of systemic lupus erythematosus in a tertiary referral center.

PubMed

Kole, Alakes Kumar; Ghosh, Alakendu

2009-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement. The skin is the second most commonly affected organ. SLE with skin lesions can produce considerable morbidity resulting from painful skin lesions, alopecia, disfigurement, etc. Skin lesions in patients with lupus may be specific (LE specific) or may be non specific (LE non specific). Acute cutaneous LE (Lupus specific) has a strong association with systemic disease and non-specific skin lesions always indicate disease activity for which patients present to rheumatologists and internists. Therefore, a thorough understanding of the cutaneous manifestations of SLE is essential for most efficient management. The aims of this study were to evaluate the patterns and prevalence of skin lesions in patients with SLE and to assess the relationship between skin lesions and other systemic involvement. At the Department of Rheumatology and Clinical Immunology, IPGME&R in Kolkata, 150 patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatology Association (updated 1982) were examined and followed-up for cutaneous manifestations between January 2002 and January 2007. Skin lesions were important clinical features. About 45 patients (30%) presented with skin lesions although all patients had skin lesions during the follow-up period. Skin changes noted were as follows: Lupus specific lesions: malar rash in 120 patients (80%), photosensitive dermatitis in 75 patients (50%), generalized maculopapular rash in 40 patients (26.67%), discoid rash in 30 patients (20%), subacute cutaneous lupus erythematosus (SCLE) in 5 patients (3.34%), lupus profundus in 5 patients (3.34%). The lupus non-specific lesions were non-scarring alopecia in 130 patients (86.67%), oral ulcers in 85 patients (56.67%), vasculitic lesions in 50 patients (33.34%), bullous lesions in 15 patients (10%), Raynaud's phenomenon in 10 patients (6.67%), pyoderma gangrenosum in 2 patients (1

Cohort Profile: The Malaysian Cohort (TMC) project: a prospective study of non-communicable diseases in a multi-ethnic population

PubMed Central

Jamal, Rahman; Syed Zakaria, Syed Zulkifli; Kamaruddin, Mohd Arman; Abd Jalal, Nazihah; Ismail, Norliza; Mohd Kamil, Norkhamiwati; Abdullah, Noraidatulakma; Baharudin, Norhafizah; Hussin, Noor Hamidah; Othman, Hanita; Mahadi, Nor Muhammad

2015-01-01

The Malaysian Cohort study was initiated in 2005 by the Malaysian government. The top-down approach to this population-based cohort study ensured the allocation of sufficient funding for the project which aimed to recruit 100 000 individuals aged 35–70 years. Participants were recruited from rural and urban areas as well as from various socioeconomic groups. The main objectives of the study were to identify risk factors, to study gene-environment interaction and to discover biomarkers for the early detection of cancers and other diseases. At recruitment, a questionnaire-based interview was conducted, biophysical measurements were performed and biospecimens were collected, processed and stored. Baseline investigations included fasting blood sugar, fasting lipid profile, renal profile and full blood count. From April 2006 to the end of September 2012 we recruited a total of 106 527participants. The baseline prevalence data showed 16.6% participants with diabetes, 46.5% with hypertension, 44.9% with hypercholesterolaemia and 17.7% with obesity. The follow-up phase commenced in June 2013. This is the most comprehensive and biggest cohort study in Malaysia, and has become a valuable resource for epidemiological and biological research. For information on collaboration and also data access, investigators can contact the project leader at (rahmanj@ppukm.ukm.edu.my). PMID:24729425

Drug-induced lupus erythematosus

MedlinePlus

... Tsokos GC, ed. Systemic Lupus Erythematosus . Philadelphia, PA: Elsevier; 2016:chap 54. Habif TP. Connective tissue diseases. ... TP, ed. Clinical Dermatology . 6th ed. Philadelphia, PA: Elsevier; 2016:chap 17. Kumar V, Abbas AK, Aster ...

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States.

PubMed

Jarukitsopa, Sudumpai; Hoganson, Deana D; Crowson, Cynthia S; Sokumbi, Olayemi; Davis, Mark D; Michet, Clement J; Matteson, Eric L; Maradit Kremers, Hilal; Chowdhary, Vaidehi R

2015-05-01

Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993-2005. SLE cases were identified from review of medical records and fulfilled the 1982 American College of Rheumatology classification criteria. CLE cases included patients with classic discoid lupus erythematosus, subacute CLE, lupus panniculitis, and bullous lupus erythematosus. Age- and sex-adjusted incidence and prevalence were standardized to the 2000 US white population. The age- and sex-adjusted incidence of SLE (2.9 per 100,000; 95% confidence interval [95% CI] 2.0-3.7) was similar to that of CLE (4.2 per 100,000; 95% CI 3.1-5.2, P = 0.10). However, the incidence of CLE was 3 times higher than SLE in men (2.4 versus 0.8 per 100,000; P = 0.009). The age- and sex-adjusted prevalence of CLE on January 1, 2006 was higher than that of SLE (70.4 versus 30.5 per 100,000; P < 0.001). The prevalences of CLE and SLE in women were similar, but the prevalence of CLE was higher in men than in women (56.9 versus 1.6 per 100,000; P < 0.001). The incidence of CLE rose steadily with age and peaked at 60-69 years. The incidences of CLE and SLE are similar, but CLE is more common than SLE in men and in older adults. These findings may reflect differences in genetic or environmental etiology of CLE. © 2015, American College of Rheumatology.

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study