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Sample records for autoimmune liver disease

  1. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  2. Autoantibodies in autoimmune liver diseases.

    PubMed

    Sener, Asli Gamze

    2015-11-01

    Autoimmune hepatitis is a chronic hepatitis of unknown etiology characterized by clinical, histological, and immunological features, generally including circulating autoantibodies and a high total serum and/or gamma globulin. Liver-related autoantibodies are very significant for the correct diagnosis and classification of autoimmune liver diseases (AILD), namely autoimmune hepatitis types 1 and 2 (AIH-1 and 2), primary biliary cirrhosis (PBC), and the sclerosing cholangitis types in adults and children. This article intends to review recent studies that investigate autoantibodies in autoimmune liver diseases from a microbiological perspective.

  3. Fibrosis in Autoimmune and Cholestatic Liver Disease

    PubMed Central

    Penz-Österreicher, Melitta; Österreicher, Christoph H.; Trauner, Michael

    2011-01-01

    Autoimmune and cholestatic liver disease account for a significant part of end-stage liver disease and are leading indications for liver transplantation. Especially cholestatic liver diseases (primary biliary cirrhosis and primary sclerosing cholangitis) appear to be different from other chronic liver diseases with regards to pathogenesis. Portal fibroblasts located in the connective tissue surrounding bile ducts appear to be different from hepatic stellate cells with regards to expression of marker proteins and response the profibrogenic and mitogenic stimuli. In addition there is increasing evidence for a cross talk between activated cholangiocytes and portal myofibroblasts. Several animal models have improved our understanding of the mechanisms underlying these chronic liver diseases. In the present review, we discuss the current concepts and ideas with regards to myofibroblastic cell populations, mechanisms of fibrosis, summarize characteristic histological findings and currently employed animal models of autoimmune and cholestatic liver disease. PMID:21497742

  4. Recurrence of autoimmune liver diseases after liver transplantation

    PubMed Central

    Faisal, Nabiha; Renner, Eberhard L

    2015-01-01

    Liver transplantation (LT) is the most effective treatment modality for end stage liver disease caused by many etiologies including autoimmune processes. That said, the need for transplantation for autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), but not for primary sclerosing cholangitis (PSC), has decreased over the years due to the availability of effective medical treatment. Autoimmune liver diseases have superior transplant outcomes than those of other etiologies. While AIH and PBC can recur after LT, recurrence is of limited clinical significance in most, but not all cases. Recurrent PSC, however, often progresses over years to a stage requiring re-transplantation. The exact incidence and the predisposing factors of disease recurrence remain debated. Better understanding of the pathogenesis and the risk factors of recurrent autoimmune liver diseases is required to develop preventive measures. In this review, we discuss the current knowledge of incidence, diagnosis, risk factors, clinical course, and treatment of recurrent autoimmune liver disease (AIH, PBC, PSC) following LT. PMID:26689244

  5. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  6. Treatment of autoimmune liver disease: current and future therapeutic options

    PubMed Central

    Trivedi, Palak J.

    2013-01-01

    Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice. PMID:23634279

  7. Current Status of Therapy in Autoimmune Liver Disease

    PubMed Central

    Al-Harthi, Nadya; Heathcote, E. Jenny

    2009-01-01

    Therapeutic strategies for autoimmune liver diseases are increasingly established. Although proportionately uncommon, specialist centers have with time refined the best approaches for each disease, based on an improved understanding of the spectrum of presentation. The major treatment aims are to prevent end-stage liver disease and its associated complications. As a result of drugs such as ursodeoxycholic acid, predniso(lo)ne and azathioprine, both primary biliary cirrhosis and autoimmune hepatitis are now less commonly indications for liver transplantation. Unfortunately, the same inroads in treatment efficacy have as yet not been made for primary sclerosing cholangitis, although the recognition that a subset of patients may have a treatable secondary sclerosing cholangitis (IgG4 related) is helping a proportion. With better biological understanding, more specific interventions are expected that will benefit all those with autoimmune liver diseases. PMID:21180531

  8. NK Cell Subtypes as Regulators of Autoimmune Liver Disease

    PubMed Central

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  9. NK Cell Subtypes as Regulators of Autoimmune Liver Disease.

    PubMed

    Jiao, Guohui; Wang, Bangmao

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal "self" cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a "two-edged weapon" and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  10. Acute viral E hepatitis with chronic liver disease (autoimmune hepatitis).

    PubMed

    Desai, H G; Naik, A S

    2005-03-01

    A 36 years old male presented with anorexia, jaundice and ascites. He was suffering from acute viral E hepatitis. In view of ascites, he was investigated for associated asymptomatic chronic liver disease (CLD). The CLD was diagnosed as cirrhosis with autoimmune hepatitis and was treated with steroid with good response. He is maintaining good health with low dose steroid, on follow up for 1 year.

  11. Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

    PubMed

    Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

    2016-02-01

    The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

  12. Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

    PubMed

    Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

    2016-02-01

    The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis. PMID:26408009

  13. Therapeutic Potential of IL-17-Mediated Signaling Pathway in Autoimmune Liver Diseases

    PubMed Central

    Zhang, Haiyan; Bernuzzi, Francesca; Lleo, Ana; Ma, Xiong; Invernizzi, Pietro

    2015-01-01

    Emerging evidence reveals that various cytokines and tissue microenvironments contribute to liver inflammation and autoimmunity, and IL-17 family is one of highlights acknowledged. Although the implication of IL-17 family in most common autoimmune diseases (such as psoriasis, inflammatory bowel disease, and rheumatoid arthritis) has been extensively characterized, the role of this critical family in pathophysiology of autoimmune liver diseases (AILD) still needs to be clarified. In the review, we look into the intriguing biology of IL-17 family and further dissect on the intricate role of IL-17-mediated pathway in AILD. Considering encouraging data from preclinical and clinical trials, IL-17 targeted therapy has shown promises in several certain autoimmune conditions. However, blocking IL-17-mediated pathway is just beginning, and more fully investigation and reflection are required. Taking together, targeting IL-17-mediated responses may open up new areas of potential clinical treatment for AILD. PMID:26146463

  14. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists.

    PubMed

    Trivedi, Palak J; Corpechot, Christophe; Pares, Albert; Hirschfield, Gideon M

    2016-02-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644-659). PMID:26290473

  15. Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

    PubMed Central

    Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

    2015-01-01

    Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

  16. The impact of immune dysregulation on the development of autoimmune gastrointestinal and liver disease.

    PubMed

    Levine, Jeremiah

    2014-12-01

    The intestinal epithelium plays an active immunologic role in preventing the uptake of foreign antigens. Additionally, the intestinal mucosa is an active site for immune suppression through the development of oral tolerance. Dysfunction of any aspect of the intestinal barrier, such as impairment of intestinal tight junctions, immunologic dysregulation or decreased oral tolerance will lead to overstimulation of the immune system upon exposure to foreign antigens and subsequent unregulated chronic intestinal inflammation. This persistent inflammatory activity may potentially predispose the patient to the development of intestinal autoimmune disease. An active immune response possibly directed against intestinal flora has been postulated to be the underlying etiology for inflammatory bowel disease. Failure of oral tolerance is thought predispose a patient to celiac disease and possibly eosinophilic esophagitis. Additionally, an active immunologic response to absorbed antigen may be the underlying etiology for the development of autoimmune liver disease.

  17. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver.

    PubMed

    Bittencourt, Paulo Lisboa; Cançado, Eduardo Luiz Rachid; Couto, Cláudia Alves; Levy, Cynthia; Porta, Gilda; Silva, Antônio Eduardo Benedito; Terrabuio, Debora Raquel Benedita; Carvalho Filho, Roberto José de; Chaves, Dalton Marques; Miura, Irene Kazue; Codes, Liana; Faria, Luciana Costa; Evangelista, Andreia Silva; Farias, Alberto Queiroz; Gonçalves, Luciana Lofêgo; Harriz, Michele; Lopes Neto, Edmundo Pessoa A; Luz, Gustavo Oliveira; Oliveira, Patrícia; Oliveira, Elze Maria Gomes de; Schiavon, Janaina Luz Narciso; Seva-Pereira, Tiago; Parise, Edison Roberto

    2015-12-01

    In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology.

  18. Brazilian society of hepatology recommendations for the diagnosis and management of autoimmune diseases of the liver.

    PubMed

    Bittencourt, Paulo Lisboa; Cançado, Eduardo Luiz Rachid; Couto, Cláudia Alves; Levy, Cynthia; Porta, Gilda; Silva, Antônio Eduardo Benedito; Terrabuio, Debora Raquel Benedita; Carvalho Filho, Roberto José de; Chaves, Dalton Marques; Miura, Irene Kazue; Codes, Liana; Faria, Luciana Costa; Evangelista, Andreia Silva; Farias, Alberto Queiroz; Gonçalves, Luciana Lofêgo; Harriz, Michele; Lopes Neto, Edmundo Pessoa A; Luz, Gustavo Oliveira; Oliveira, Patrícia; Oliveira, Elze Maria Gomes de; Schiavon, Janaina Luz Narciso; Seva-Pereira, Tiago; Parise, Edison Roberto

    2015-12-01

    In order to draw evidence-based recommendations concerning the management of autoimmune diseases of the liver, the Brazilian Society of Hepatology has sponsored a single-topic meeting in October 18th, 2014 at São Paulo. An organizing committee comprised of seven investigators was previously elected by the Governing Board to organize the scientific agenda as well as to select twenty panelists to make a systematic review of the literature and to present topics related to the diagnosis and treatment of autoimmune hepatitis, primary sclerosing cholangitis, primary biliary cirrhosis and their overlap syndromes. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript organized in topics, followed by the recommendations of the Brazilian Society of Hepatology. PMID:26959804

  19. The autoimmune diseases

    SciTech Connect

    Rose, N.R.; Mackay, I.R.

    1985-01-01

    This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.

  20. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. PMID:27503128

  1. Familial occurrence of autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis in a mother and her daughter.

    PubMed

    Omori, Kaoru; Yoshida, Kanako; Yokota, Masaki; Daa, Tsutomu; Kan, Masahiro

    2016-10-01

    We encountered two patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family. A 68-year-old woman presented at our hospital from a previous medical institution because of the diagnosis of primary biliary cholangitis. Her 49-year-old daughter was admitted with liver dysfunction 4 years later. When compared, these two related patients were found to have overlapping features of primary biliary cholangitis and autoimmune hepatitis. Their human leukocyte antigen haplotype was DRB1*04:05/DRB1*15:02. The clinical and biochemical findings of these two patients immediately improved following treatment with a combination of prednisolone and ursodeoxycholic acid, in accordance with the Japanese guidelines. It is extremely important to identify such pathological conditions as quickly as possible, particularly with the appearance of severe liver dysfunction due to liver cirrhosis, as observed in our case. The Japanese guidelines are considered to be a realistic and useful clinical policy for the swift and efficient treatment of patients with overlapping features of primary biliary cholangitis and autoimmune hepatitis. We suggest that our two patients presented with a genetic predisposition to autoimmune liver disease with overlapping features of primary biliary cholangitis and autoimmune hepatitis within the same family.

  2. Autoimmune Inner Ear Disease

    MedlinePlus

    ... Find an ENT Doctor Near You Autoimmune Inner Ear Disease Autoimmune Inner Ear Disease Patient Health Information ... with a hearing loss. How Does the Healthy Ear Work? The ear has three main parts: the ...

  3. [Interferons and autoimmune diseases].

    PubMed

    Niino, Masaaki; Miyazaki, Yusei

    2013-11-01

    Interferons are widely expressed cytokines that have potent antiviral, antiproliferative, and immunomodulatory effects. Type I interferons show complex biology; in some cases, they promote autoimmunity and inflammation, and in other cases, exhibit homeostatic functions by controlling inflammation and tissue destruction. This complexity is exemplified in the 2 major autoimmune diseases: systemic lupus erythematosus, in which type I interferons play an important role in the pathogenesis, and multiple sclerosis, in which interferon beta, a type I interferon, exhibits protective and therapeutic roles. This article reviews the basic clinical data on type I interferons in autoimmune diseases and type I interferons as potential targets for therapies in autoimmune diseases.

  4. American Autoimmune Related Diseases Association

    MedlinePlus

    ... With #25FOR25 Campaign During National Autoimmune Disease Awareness Month AARDA officially kicks of National Autoimmune Disease Awareness ... Click here to read more. Autoimmune Disease Awareness Month AARDA and the NCAPG held two important events ...

  5. [De novo autoimmune hepatitis after liver transplantation].

    PubMed

    Luo, Bifen; Wei, Lai

    2016-02-01

    Patients who transplanted for non-autoimmune indication may developed de novo autoimmune hepatitis after liver transplantation. It happens about 1.7%-6.6% in liver transplanted population. Most patients with de novo AIH had transplanted for HCV infection, biliary atresia and Cholestatic liver disease. The interval between transplantation and de novo AIH onset is from 3 month to 16 years, mostly more than 1 year. The disease can be seen at any age. More female patients are present in children, while there is no significant difference between male and female in adults. Clinical manifestations of de novo AIH are similar to those of AIH, namely characterized by elevated transaminase with or without bilirubin, as well as elevated serum gammaglobulin (IgG) and positive autoantibodies, while the histological features of an infiltrate rich in plasma cells with interface hepatitis and necro-inflammation and fibrosis. Treatment with corticosteroids and Azathioprine brings good outcomes, but it tends to fluctuate.

  6. Autoimmune diseases and vaccinations.

    PubMed

    Vial, Thierry; Descotes, Jacques

    2004-01-01

    The potential association between vaccination and autoimmune diseases has been largely questioned in the past few years, but this assumption has mostly been based on case reports. The available evidence derived from several negative epidemiological studies is reassuring and at least indicates that vaccines are not a major cause of autoimmune diseases. However, there are still uncertainties as to whether a susceptible subpopulation may be at a higher risk of developing an autoimmune disease without causing an overall increase in the disease incidence. Based on selected examples, this review highlights the difficulties in assessing this issue. We suggest that a potential link between vaccines and autoimmune diseases cannot be definitely ruled out and should be carefully explored during the development of new candidate vaccines. PMID:15196997

  7. Understanding Autoimmune Diseases

    MedlinePlus

    ... Autoimmune Diseases Progress and Promise Key Words The Immune System Your immune system is the network of cells and tissues throughout ... having two parts: the acquired and the innate immune systems. The acquired (or adaptive) immune system develops as ...

  8. Autoimmune disease and pregnancy.

    PubMed

    Jones, W R

    1994-06-01

    Autoimmune diseases are relatively common in women, and tend to occur in the childbearing years. These disorders fall broadly into two groups: (i) Multisystem diseases such as systemic lupus erythematosus (SLE) and related connective tissue disorders (CTD). This group includes the 'pre-clinical' antiphospholipid or lupus obstetric syndrome which may first manifest itself as a pregnancy disorder causing recurrent abortion, fetal death, fetal growth retardation and early onset severe pre-eclampsia. (ii) Tissue- or organ-specific disorders such as autoimmune thrombocytopaenic purpura (ATP), autoimmune thyroid disease (Graves' disease, Hashimoto's autoimmune thyroiditis, and post-postum thyroiditis), autoimmune haemolytic anaemia, and the very rare myasthenia gravis. The study of autoimmune diseases against the background of pregnancy as an experimental system of nature has provided important insights into the nature of the disease processes and the relevance or otherwise of circulating autoantibodies to pathological effects. Thus, for example, if neonatal manifestations of adult disease are causally related to the transfer of autoantibodies across the placenta, they will disappear over a time course consistent with the catabolism of IgG, providing no permanent damage is produced. Conversely, if autoantibodies are demonstrable in the neonate, in the absence of clinical effects, they may only be an epiphenomenon of the maternal disease. In addition, on occasions, disease manifestations may be seen in the baby when the mother shows none. This may occur when the mother is in remission, but still has circulating antibodies, or when she has an occult form of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2016-04-22

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  10. Epigenomics of autoimmune diseases.

    PubMed

    Gupta, Bhawna; Hawkins, R David

    2015-03-01

    Autoimmune diseases are complex disorders of largely unknown etiology. Genetic studies have identified a limited number of causal genes from a marginal number of individuals, and demonstrated a high degree of discordance in monozygotic twins. Studies have begun to reveal epigenetic contributions to these diseases, primarily through the study of DNA methylation, but chromatin and non-coding RNA changes are also emerging. Moving forward an integrative analysis of genomic, transcriptomic and epigenomic data, with the latter two coming from specific cell types, will provide an understanding that has been missed from genetics alone. We provide an overview of the current state of the field and vision for deriving the epigenomics of autoimmunity.

  11. De novo autoimmune hepatitis after liver transplantation.

    PubMed

    Lohse, Ansgar W; Weiler-Norman, Christina; Burdelski, Martin

    2007-10-01

    The Kings College group was the first to describe a clinical syndrome similar to autoimmune hepatitis in children and young adults transplanted for non-immune mediated liver diseases. They coined the term "de novo autoimmune hepatitis". Several other liver transplant centres confirmed this observation. Even though the condition is uncommon, patients with de novo AIH are now seen in most of the major transplant centres. The disease is usually characterized by features of acute hepatitis in otherwise stable transplant recipients. The most characteristic laboratory hallmark is a marked hypergammaglobulinaemia. Autoantibodies are common, mostly ANA. We described also a case of LKM1-positivity in a patients transplanted for Wilson's disease, however this patients did not develop clinical or histological features of AIH. Development of SLA/LP-autoantibodies is also not described. Therefore, serologically de novo AIH appears to correspond to type 1 AIH. Like classical AIH patients respond promptly to treatment with increased doses of prednisolone and azathioprine, while the calcineurin inhibitors cyclosporine or tacrolimus areof very limited value - which is not surprising, as almost all patients develop de novo AIH while receiving these drugs. Despite the good response to treatment, most patients remain a clinical challenge as complete stable remissions are uncommon and flares, relapses and chronic disease activity can often occur. Pathogenetically this syndrome is intriguing. It is not clear, if the immune response is directed against allo-antigens, neo-antigens in the liver, or self-antigens, possibly shared by donor and host cells. It is very likely that the inflammatory milieu due to alloreactive cells in the transplanted organ contribute to the disease process. Either leading to aberrant antigen presentation, or providing co-stimulatory signals leading to the breaking of self-tolerance. The development of this disease in the presence of treatment with calcineurin

  12. Galectin-3 in autoimmunity and autoimmune diseases

    PubMed Central

    de Oliveira, Felipe L; Gatto, Mariele; Bassi, Nicola; Luisetto, Roberto; Ghirardello, Anna; Punzi, Leonardo

    2015-01-01

    Galectin-3 (gal-3) is a β-galactoside-binding lectin, which regulates cell–cell and extracellular interactions during self/non-self-antigen recognition and cellular activation, proliferation, differentiation, migration and apoptosis. It plays a significant role in cellular and tissue pathophysiology by organizing niches that drive inflammation and immune responses. Gal-3 has some therapeutic potential in several diseases, including chronic inflammatory disorders, cancer and autoimmune diseases. Gal-3 exerts a broad spectrum of functions which differs according to its intra- or extracellular localization. Recombinant gal-3 strategy has been used to identify potential mode of action of gal-3; however, exogenous gal-3 may not reproduce the functions of the endogenous gal-3. Notably, gal-3 induces monocyte–macrophage differentiation, interferes with dendritic cell fate decision, regulates apoptosis on T lymphocytes and inhibits B-lymphocyte differentiation into immunoglobulin secreting plasma cells. Considering the influence of these cell populations in the pathogenesis of several autoimmune diseases, gal-3 seems to play a role in development of autoimmunity. Gal-3 has been suggested as a potential therapeutic agent in patients affected with some autoimmune disorders. However, the precise role of gal-3 in driving the inflammatory process in autoimmune or immune-mediated disorders remains elusive. Here, we reviewed the involvement of gal-3 in cellular and tissue events during autoimmune and immune-mediated inflammatory diseases. PMID:26142116

  13. Rituximab in autoimmune diseases

    PubMed Central

    Randall, Katrina L

    2016-01-01

    SUMMARY Rituximab is a monoclonal antibody that depletes B cells from the circulation. It was originally used to treat lymphoma but is increasingly used for the treatment of autoimmune diseases. Rituximab was found to be effective in randomised controlled trials for rheumatoid arthritis, granulomatosis with polyangiitis and other antineutrophil cytoplasmic antibody-associated vasculitides. However, evidence of efficacy is very limited for many other autoimmune conditions. Before starting rituximab, it is important to check the patient’s baseline immunoglobulins and immunisation status. Patients should also be screened for latent infections and other contraindications. PMID:27756976

  14. Liver Diseases

    MedlinePlus

    ... remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis A, ... the skin, can be one sign of liver disease. Cancer can affect the liver. You could also ...

  15. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the liver ...

  16. Endothelial damage and autoimmune diseases.

    PubMed

    Kaplan, Mariana J

    2009-11-01

    This issue of Autoimmunity reviews the mechanisms that lead to vascular damage in systemic autoimmune diseases. In addition, this issue explores recent advances in the understanding of how abnormalities in angiogenesis present in autoimmune diseases may lead to tissue damage and/or to premature vascular disease.

  17. [Autoimmune Diseases of Digestive System].

    PubMed

    Ivashkinl, V T; Sheptulina, A F; Raĭkhelson, K L; Losik, E A; Ivashkin, K V; Okhlobystin, A V; Baranskaia, E K; Polouvektova, E A; Shifrin, O S

    2015-01-01

    Autoimmune diseases of digestive system refer to pathological conditions, caused by autoimmune mechanisms, and their etiology remains unknown. This is a group of relatively rare diseases, however, during the last years a marked tendency towards the raise in incidence andprevalence is observed, which led to an increase in number of clinical investigations on etiology, pathogenesis, and, accordingly, development of new diagnostic methods and therapies. Results of such trials shown, for example, that the pathogenesis of chronic cholestatic liver diseases is associated with nuclear receptors function, while the main etiological and pathogenic factor of inflammatory bowel diseases represents gut microbiota. Despite new achievements in autoinmune diseases of digestive system research, therapies are low effective and are accompanied by a huge number of adverse events. The fact that these diseases may lead to malignant tumors is also worth noting. For example, patients with primary sclerosing cholangitis have a 160 times higher risk of cholangiocellular carcinoma, while 10-14% ofpatients with celiac disease may develop malignancies of esophagus, small and large intestine. Thus, these diseases require further investigation with a purpose of more accurate diagnostic methods for the detection of disease at early stages and new effective and safe therapies development.

  18. Delineating liver events in trichloroethylene-induced autoimmune hepatitis.

    PubMed

    Gilbert, Kathleen M; Przybyla, Beata; Pumford, Neil R; Han, Tao; Fuscoe, James; Schnackenberg, Laura K; Holland, Ricky D; Doss, Jason C; Macmillan-Crow, Lee Ann; Blossom, Sarah J

    2009-04-01

    Exposure to the environmental pollutant trichloroethylene (TCE) has been linked to autoimmune disease development in humans. Chronic (32-week) low-level exposure to TCE has been shown to promote autoimmune hepatitis in association with CD4(+) T cell activation in autoimmune-prone MRL+/+ mice. MRL+/+ mice are usually thought of as a model of systemic lupus rather than an organ-specific disease such as autoimmune hepatitis. Consequently, the present study examined gene expression and metabolites to delineate the liver events that skewed the autoimmune response toward that organ in TCE-treated mice. Female MRL+/+ mice were treated with 0.5 mg/mL TCE in their drinking water. The results showed that TCE-induced autoimmune hepatitis could be detected in as little as 26 weeks. TCE exposure also generated a time-dependent increase in the number of antibodies specific for liver proteins. The gene expression correlated with the metabolite analysis to show that TCE upregulated the methionine/homocysteine pathway in the liver after 26 weeks of exposure. The results also showed that TCE exposure altered the expression of selective hepatic genes associated with immunity and inflammation. On the basis of these results, future mechanistic studies will focus on how alterations in genes associated with immunity and inflammation, in conjunction with protein alterations in the liver, promote liver immunogenicity in TCE-treated MRL+/+ mice.

  19. Longterm corticosteroid use after liver transplantation for autoimmune hepatitis is safe and associated with a lower incidence of recurrent disease.

    PubMed

    Krishnamoorthy, Thinesh L; Miezynska-Kurtycz, Joanna; Hodson, James; Gunson, Bridget K; Neuberger, James; Milkiewicz, Piotr; Oo, Ye H

    2016-01-01

    Patients transplanted for autoimmune hepatitis (AIH) are at risk of recurrent disease. Our current practice is to maintain long-term low-dose corticosteroids with additional immunosuppressive agents. This study describes the implications on patients' outcomes, sepsis, and osteoporosis. We collected data on patients transplanted between January 1999 and October 2014 in a single center who survived for more than 6 months. AIH recurrence was diagnosed by a combination of histology, raised immunoglobulin G levels, and exclusion of other etiologies. Sepsis was defined as any infection that resulted in significant morbidity or mortality. Osteoporosis was defined as a bone densitometry T score of less than -2.0 or evidence of osteoporosis-related fractures. Outcomes were assessed using Kaplan-Meier survival analysis methods. Seventy-three AIH patients underwent liver transplantation with a median follow-up of 94 months (interquartile range, 55-144). The cohort was mainly Caucasian (78%), female (79%), with type 1 AIH (90%), and a mean age of 43 ± 15 years. Overall survival was 92%, 90%, 86%, and 73%, and regraft-free survival was 86%, 81%, 78%, and 64% at 1, 3, 5, and 10 years, respectively. Five patients developed AIH recurrence, giving recurrence rates of 0%, 4%, 6%, and 11% at 1, 3, 5, and 10 years, respectively. Pneumonia was the most common infection, but gastroenteritis and cholangitis were the most recurrent. Freedom from sepsis was 91%, 82%, 80%, and 63%, and freedom from osteoporosis was 100%, 94%, 82%, and 58% at 1, 3, 5, and 10 years, respectively. Longterm low-dose corticosteroid in combination with other immunosuppressive agents seems to reduce AIH recurrence without jeopardizing patient and graft survival. Sepsis and osteoporosis did not occur more often compared to the published literature on liver transplant recipients. PMID:26335026

  20. Autoimmune Addison's disease.

    PubMed

    Napier, Catherine; Pearce, Simon H S

    2012-12-01

    Addison's disease is a rare autoimmune disorder. In the developed world, autoimmune adrenalitis is the commonest cause of primary adrenal insufficiency, where the majority of patients have circulating antibodies against the key steroidogenic enzyme 21-hydroxylase. A complex interplay of genetic, immunological and environmental factors culminates in symptomatic adrenocortical insufficiency, with symptoms typically developing over months to years. Biochemical evaluation and further targeted investigations must confirm primary adrenal failure and establish the underlying aetiology. The diagnosis of adrenocortical insufficiency will necessitate lifelong glucocorticoid and mineralocorticoid replacement therapy, aiming to emulate physiological patterns of hormone secretion to achieve well-being and good quality of life. Education of patients and healthcare professionals is essential to minimise the risk of a life-threatening adrenal crisis, which must be promptly recognised and aggressively managed when it does occur. This article provides an overview of our current understanding of the natural history and underlying genetic and immunological basis of this condition. Future research may reveal novel therapeutic strategies for patient management. Until then, optimisation of pharmacological intervention and continued emphasis on education and empowerment of patients should underpin the management of individuals with autoimmune Addison's disease.

  1. [Hydroxychloroquine for autoimmune diseases].

    PubMed

    Danza, Álvaro; Graña, Diego; Goñi, Mabel; Vargas, Andrea; Ruiz-Irastorza, Guillermo

    2016-02-01

    Hydroxychloroquine (HCQ) is by far the most frequently used antimalarial for the management of Systemic Autoimmune Diseases. It has immunomodulatory, hypolipidemic, hypoglycemic and antithrombotic properties and it diminishes the risk of malignancies. The most important mechanisms to explain the immunomodulatory actions are its ability to reduce inflammatory pathways and Toll-like receptors activation. The safety profile is favorable. In spite of its low frequency, retinal toxicity is potentially severe. In systemic lupus erythematous HCQ therapy reduces activity, the accrual of organ damage, risk of infections and thrombosis and improves the cardiometabolic profile. It contributes to induce lupus nephritis remission, spares steroid use and increases survival rates. In rheumatoid arthritis, it improves cardiometabolic risk and has a favorable effect in joint inflammation. In Sjögren's syndrome, an increased lacrimal quality as well as an improvement in objective and subjective inflammatory markers has been demonstrated with HCQ. In Antiphospholipid Syndrome, HCQ is effective in primary and secondary thrombosis prevention. The effectiveness of the drug in other systemic autoimmune diseases is less established. HCQ therapy may improve dermatological manifestations in Dermatomyositis and may have a positive effects in the treatment of Sarcoidosis and Still disease. PMID:27092678

  2. Autoimmune muscle disease.

    PubMed

    Mammen, Andrew

    2016-01-01

    Patients with polymyositis (PM), dermatomyositis (DM), and immune-mediated necrotizing myopathy (IMNM) present with the subacute onset of symmetric proximal muscle weakness, elevated muscle enzymes, myopathic findings on electromyography, and autoantibodies. DM patients are distinguished by their cutaneous manifestations. Characteristic features on muscle biopsy include the invasion of nonnecrotic muscle fibers by T cells in PM, perifascicular atrophy in DM, and myofiber necrosis without prominent inflammation in IMNM. Importantly, these are regarded as autoimmune diseases and most patients respond partially, if not completely, to immunosuppressive therapy. Patients with inclusion body myositis (IBM) usually present with the insidious onset of asymmetric weakness in distal muscles (e.g., wrist flexors, and distal finger flexors), often when more proximal muscle groups are relatively preserved. Although IBM muscle biopsies usually have focal invasion of myofibers by lymphocytes, the majority of IBM biopsies also include rimmed vacuoles. While most IBM patients do have autoantibodies, treatment with immunosuppressive agents does not improve their clinical course. Along with the presence of abnormally aggregated proteins on muscle biopsy, the refractory nature and relentless course of IBM suggest that the underlying pathophysiology may include a dominant myodegenerative component. This chapter will focus on the epidemiology, clinical presentation, and treatment of the autoimmune myopathies and IBM. An emphasis will be placed on recent advances, indicating that these are a diverse family of diseases and that each of more than a dozen myositis autoantibodies is associated with a distinct clinical phenotype. PMID:27112692

  3. A molecular marker of disease activity in autoimmune liver diseases with histopathological correlation; FoXp3/RORγt ratio.

    PubMed

    Mitra, Suvradeep; Anand, Shashi; Das, Ashim; Thapa, Baburam; Chawla, Yogesh Kumar; Minz, Ranjana Walker

    2015-11-01

    Autoimmune liver diseases (AILDs) encompass a group of diseases with variable clinicopathological manifestations. Th17 and Treg cells have roles in the pathogenesis of AILDs with a balance shifted towards a relative increase in activity of the Th17 cells. In this study, the balance between the transcription factors of Treg and Th17 cells (FoXp3 and RORγt) was sought as a molecular marker of disease activity and to highlight the pathogenesis. The peripheral blood samples of 46 treatment-naive patients were collected and RNA was extracted. Real time PCR was performed and the ratio of gene expression was calculated. Histopathology of 18 patients was obtained and the activity score of these biopsies were also corroborated with their respective molecular (FoXp3/RORγt) (FRGT=FoXp3-ROR Gamma T) ratio. The FRGT ratio in healthy individuals was close to 1 and in disease the ratio changed significantly. This ratio (FRGT) was not significantly different in different varieties of AILD or in adult or paediatric form of the disease. However, the ratio remained consistently below 1 (mean 0.3) in acute disease and high (mean 224.7) in chronic or asymptomatic form of the disease (p < 0.001). The histopathological activity score also significantly correlated with the ratio. This signified the relative excess of Th17 (RORγt) in active disease as compared to Treg (FoXp3) and the reverse in chronic form. This ratio can be an important peripheral molecular marker to assess the disease activity without the necessity of performing a liver biopsy.

  4. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation. PMID:26875020

  5. Autoimmune diseases and myelodysplastic syndromes.

    PubMed

    Komrokji, Rami S; Kulasekararaj, Austin; Al Ali, Najla H; Kordasti, Shahram; Bart-Smith, Emily; Craig, Benjamin M; Padron, Eric; Zhang, Ling; Lancet, Jeffrey E; Pinilla-Ibarz, Javier; List, Alan F; Mufti, Ghulam J; Epling-Burnette, Pearlie K

    2016-05-01

    Immune dysregulation and altered T-cell hemostasis play important roles in the pathogenesis of myelodysplastic syndromes (MDS). Recent studies suggest an increased risk of MDS among patients with autoimmune diseases. Here, we investigated the prevalence of autoimmune diseases among MDS patients, comparing characteristics and outcomes in those with and without autoimmune diseases. From our study group of 1408 MDS patients, 391 (28%) had autoimmune disease, with hypothyroidism being the most common type, accounting for 44% (n = 171) of patients (12% among all MDS patients analyzed). Other autoimmune diseases with ≥5% prevalence included idiopathic thrombocytopenic purpura in 12% (n = 46), rheumatoid arthritis in 10% (n = 41), and psoriasis in 7% (n = 28) of patients. Autoimmune diseases were more common in female MDS patients, those with RA or RCMD WHO subtype, and those who were less dependent on red blood cell transfusion. Median overall survival (OS) was 60 months (95% CI, 50-70) for patients with autoimmune diseases versus 45 months (95% CI, 40-49) for those without (log-rank test, P = 0.006). By multivariate analysis adjusting for revised IPSS and age >60 years, autoimmune diseases were a statistically significant independent factor for OS (HR 0.78; 95% CI, 0.66-0.92; P = 0.004). The rate of acute myeloid leukemia (AML) transformation was 23% (n = 89) in MDS patients with autoimmune disease versus 30% (n = 301) in those without (P = 0.011). Patient groups did not differ in response to azacitidine or lenalidomide treatment. Autoimmune diseases are prevalent among MDS patients. MDS patients with autoimmune diseases have better OS and less AML transformation.

  6. Mast Cell and Autoimmune Diseases

    PubMed Central

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  7. Mast cell and autoimmune diseases.

    PubMed

    Xu, Yunzhi; Chen, Guangjie

    2015-01-01

    Mast cells are important in innate immune system. They have been appreciated as potent contributors to allergic reaction. However, increasing evidence implicates the important role of mast cells in autoimmune disease like rheumatoid arthritis and multiple sclerosis. Here we review the current stage of knowledge about mast cells in autoimmune diseases. PMID:25944979

  8. Progesterone and Autoimmune Disease

    PubMed Central

    Hughes, Grant C.

    2011-01-01

    Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-α) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg’s immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations. PMID:22193289

  9. Sex differences in autoimmune diseases

    PubMed Central

    2011-01-01

    Women are more susceptible to a variety of autoimmune diseases including systemic lupus erythematosus (SLE), multiple sclerosis (MS), primary biliary cirrhosis, rheumatoid arthritis and Hashimoto's thyroiditis. This increased susceptibility in females compared to males is also present in animal models of autoimmune diseases such as spontaneous SLE in (NZBxNZW)F1 and NZM.2328 mice, experimental autoimmune encephalomyelitis (EAE) in SJL mice, thyroiditis, Sjogren's syndrome in MRL/Mp-lpr/lpr mice and diabetes in non-obese diabetic mice. Indeed, being female confers a greater risk of developing these diseases than any single genetic or environmental risk factor discovered to date. Understanding how the state of being female so profoundly affects autoimmune disease susceptibility would accomplish two major goals. First, it would lead to an insight into the major pathways of disease pathogenesis and, secondly, it would likely lead to novel treatments which would disrupt such pathways. PMID:21208397

  10. Immunity, tolerance and autoimmunity in the liver: A comprehensive review.

    PubMed

    Doherty, Derek G

    2016-01-01

    The hepatic immune system is constantly exposed to a massive load of harmless dietary and commensal antigens, to which it must remain tolerant. Immune tolerance in the liver is mediated by a number of specialized antigen-presenting cells, including dendritic cells, Kupffer cells, liver sinusoidal endothelial cells and hepatic stellate cells. These cells are capable of presenting antigens to T cells leading to T cell apoptosis, anergy, or differentiation into regulatory T cells. However, the hepatic immune system must also be able to respond to pathogens and tumours and therefore must be equipped with mechanisms to override immune tolerance. The liver is a site of accumulation of a number of innate lymphocyte populations, including natural killer cells, CD56(+) T cells, natural killer T cells, γδ T cells, and mucosal-associated invariant T cells. Innate lymphocytes recognize conserved metabolites derived from microorganisms and host cells and respond by killing target cells or promoting the differentiation and/or activation of other cells of the immune system. Innate lymphocytes can promote the maturation of antigen-presenting cells from their precursors and thereby contribute to the generation of immunogenic T cell responses. These cells may be responsible for overriding hepatic immune tolerance to autoantigens, resulting in the induction and maintenance of autoreactive T cells that mediate liver injury causing autoimmune liver disease. Some innate lymphocyte populations can also directly mediate liver injury by killing hepatocytes or bile duct cells in murine models of hepatitis, whilst other populations may protect against liver disease. It is likely that innate lymphocyte populations can promote or protect against autoimmune liver disease in humans and that these cells can be targeted therapeutically. Here I review the cellular mechanisms by which hepatic antigen-presenting cells and innate lymphocytes control the balance between immunity, tolerance and

  11. Immunity, tolerance and autoimmunity in the liver: A comprehensive review.

    PubMed

    Doherty, Derek G

    2016-01-01

    The hepatic immune system is constantly exposed to a massive load of harmless dietary and commensal antigens, to which it must remain tolerant. Immune tolerance in the liver is mediated by a number of specialized antigen-presenting cells, including dendritic cells, Kupffer cells, liver sinusoidal endothelial cells and hepatic stellate cells. These cells are capable of presenting antigens to T cells leading to T cell apoptosis, anergy, or differentiation into regulatory T cells. However, the hepatic immune system must also be able to respond to pathogens and tumours and therefore must be equipped with mechanisms to override immune tolerance. The liver is a site of accumulation of a number of innate lymphocyte populations, including natural killer cells, CD56(+) T cells, natural killer T cells, γδ T cells, and mucosal-associated invariant T cells. Innate lymphocytes recognize conserved metabolites derived from microorganisms and host cells and respond by killing target cells or promoting the differentiation and/or activation of other cells of the immune system. Innate lymphocytes can promote the maturation of antigen-presenting cells from their precursors and thereby contribute to the generation of immunogenic T cell responses. These cells may be responsible for overriding hepatic immune tolerance to autoantigens, resulting in the induction and maintenance of autoreactive T cells that mediate liver injury causing autoimmune liver disease. Some innate lymphocyte populations can also directly mediate liver injury by killing hepatocytes or bile duct cells in murine models of hepatitis, whilst other populations may protect against liver disease. It is likely that innate lymphocyte populations can promote or protect against autoimmune liver disease in humans and that these cells can be targeted therapeutically. Here I review the cellular mechanisms by which hepatic antigen-presenting cells and innate lymphocytes control the balance between immunity, tolerance and

  12. Tips for Getting a Proper Diagnosis of an Autoimmune Disease

    MedlinePlus

    ... that are suspected to be autoimmune-related. The diseases themselves can affect almost any part of the body, including the kidneys, skin, heart, liver, lymph nodes, thyroid and the central nervous system. ...

  13. Estrogens and autoimmune diseases.

    PubMed

    Cutolo, Maurizio; Capellino, Silvia; Sulli, Alberto; Serioli, Bruno; Secchi, Maria Elena; Villaggio, Barbara; Straub, Rainer H

    2006-11-01

    Sex hormones are implicated in the immune response, with estrogens as enhancers at least of the humoral immunity and androgens and progesterone (and glucocorticoids) as natural immune-suppressors . Several physiological, pathological, and therapeutic conditions may change the serum estrogen milieu and/or peripheral conversion rate, including the menstrual cycle, pregnancy, postpartum period, menopause, being elderly, chronic stress, altered circadian rhythms, inflammatory cytokines, and use of corticosteroids, oral contraceptives, and steroid hormonal replacements, inducing altered androgen/estrogen ratios and related effects. In particular, cortisol and melatonin circadian rhythms are altered, at least in rheumatoid arthritis (RA), and partially involve sex hormone circadian synthesis and levels as well. Abnormal regulation of aromatase activity (i.e., increased activity) by inflammatory cytokine production (i.e., TNF-alpha, IL-1, and IL-6) may partially explain the abnormalities of peripheral estrogen synthesis in RA (i.e., increased availability of 17-beta estradiol and possible metabolites in synovial fluids) and in systemic lupus erythematosus, as well as the altered serum sex-hormone levels and ratio (i.e., decreased androgens and DHEAS). In the synovial fluids of RA patients, the increased estrogen concentration is observed in both sexes and is more specifically characterized by the hydroxylated forms, in particular 16alpha-hydroxyestrone, which is a mitogenic and cell proliferative endogenous hormone. Local effects of sex hormones in autoimmune rheumatic diseases seems to consist mainly in modulation of cell proliferation and cytokine production (i.e., TNF-alpha, Il-1, IL-12). In this respect, it is interesting that male patients with RA seem to profit more from anti-TNFalpha strategies than do female patients. PMID:17261796

  14. Common mechanisms of autoimmune diseases (the autoimmune tautology).

    PubMed

    Anaya, Juan-Manuel

    2012-09-01

    The fact that autoimmune diseases share subphenotypes, physiopathological mechanisms and genetic factors has been called autoimmune tautology, and indicates that they have a common origin. The autoimmune phenotypes vary depending on the target cell and the affected organ, gender, ancestry, trigger factors and age at onset. Ten shared characteristics supporting this logical theory are herein reviewed.

  15. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay.

    PubMed

    Miyakawa, Hiroshi; Kawashima, Yumi; Kitazawa, Eriko; Kawaguchi, Naomi; Kato, Takashi; Kikuchi, Kentaro; Imai, Erika; Fujikawa, Hirotoshi; Hashimoto, Etsuko; Schlumberger, Wolfgang

    2003-08-01

    Anti-soluble liver antigen/liver pancreas (SLA/LP) autoantibody has been proposed to be one of the autoantibodies characterizing autoimmune hepatitis (AIH). Recently, one of the autoantigens to anti-SLA/LP was identified as a UGA suppressor tRNA-associated protein. Although the function of this protein remains unknown, the recombinant protein has been prokaryotically expressed. Using this protein as an antigen, a recombinant immunoassay for anti-SLA/LP autoantibody has been established and the frequency and significance of this autoantibody have been discussed in European countries. So, in the present study, we investigated anti-SLA/LP autoantibodies in Japanese patients with autoimmune liver diseases using the recombinant antigen ELISA and Western blot assay. Seventy-five patients with AIH type 1, 5 with AIH type 2, 46 with primary biliary cirrhosis, 10 with primary sclerosing cholangitis, 47 with chronic hepatitis C, 48 with systemic lupus erythematosus, 3 with cryptogenic hepatitis, and 40 normal controls were the subjects of the present study. Anti-SLA/LP autoantibodies were detected in only 5 of 75 (6.7%) patients with AIH type 1, but in none of the other 159 patients or 40 normal controls. The clinicopathologic features of anti-SLA/LP-positive AIH type 1, including carriers of HLA DR locus variations, were not significantly different from anti-SLA/LP-negative patients except for the mortality rate. Anti-SLA/LP autoantibody was detected at a low frequency in Japanese patients with AIH type 1 and did not significantly influence clinical features. However, since it has high disease-specificity to AIH type 1, further analysis of SLA/LP may contribute to help clarify the pathogenesis of AIH type 1.

  16. Cardiovascular disease biomarkers across autoimmune diseases.

    PubMed

    Ahearn, Joseph; Shields, Kelly J; Liu, Chau-Ching; Manzi, Susan

    2015-11-01

    Cardiovascular disease is increasingly recognized as a major cause of premature mortality among those with autoimmune disorders. There is an urgent need to identify those patients with autoimmune disease who are at risk for CVD so as to optimize therapeutic intervention and ultimately prevention. Accurate identification, monitoring and stratification of such patients will depend upon a panel of biomarkers of cardiovascular disease. This review will discuss some of the most recent biomarkers of cardiovascular diseases in autoimmune disease, including lipid oxidation, imaging biomarkers to characterize coronary calcium, plaque, and intima media thickness, biomarkers of inflammation and activated complement, genetic markers, endothelial biomarkers, and antiphospholipid antibodies. Clinical implementation of these biomarkers will not only enhance patient care but also likely accelerate the pharmaceutical pipeline for targeted intervention to reduce or eliminate cardiovascular disease in the setting of autoimmunity.

  17. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  18. Therapeutic apheresis in autoimmune diseases

    PubMed Central

    Bambauer, Rolf; Latza, Reinhard; Bambauer, Carolin; Burgard, Daniel; Schiel, Ralf

    2013-01-01

    Systemic autoimmune diseases based on an immune pathogenesis produce autoantibodies and circulating immune complexes, which cause inflammation in the tissues of various organs. In most cases, these diseases have a bad prognosis without treatment. Therapeutic apheresis in combination with immunosuppressive therapies has led to a steady increase in survival rates over the last 35 years. Here we provide an overview of the most important pathogenic aspects indicating that therapeutic apheresis can be a supportive therapy in some systemic autoimmune diseases, such as systemic lupus erythematosus, antiphospholipid syndrome, rheumatoid arthritis, and inflammatory eye disease. With the introduction of novel and effective biologic agents, therapeutic apheresis is indicated only in severe cases, such as in rapid progression despite immunosuppressive therapy and/or biologic agents, and in patients with renal involvement, acute generalized vasculitis, thrombocytopenia, leucopenia, pulmonary, cardiac, or cerebral involvement. In mild forms of autoimmune disease, treatment with immunosuppressive therapies and/or biologic agents seems to be sufficient. The prognosis of autoimmune diseases with varying organ manifestations has improved considerably in recent years, due in part to very aggressive therapy schemes.

  19. Mechanisms of alcohol liver damage: aldehydes, scavenger receptors, and autoimmunity.

    PubMed

    Duryee, Michael J; Willis, Monte S; Freeman, Thomas L; Kuszynski, Charles A; Tuma, Dean J; Klassen, Lynell W; Thiele, Geoffrey M

    2004-09-01

    While most of the investigations into the causative events in the development of alcoholic liver disease (ALD) have been focused on multiple factors, increasing interest has centered around the possible role of immune mechanisms in the pathogenesis and perpetuation of ALD. This is because many of the clinical features of ALD suggest that immune effector mechanisms may be contributing to liver tissue damage, as evidenced by the detection of circulating autoantibodies, and the presence of CD4+ and CD8+ lymphoid cells in the livers of patients with ALD. One mechanism that has been associated with the development of autoimmune responses is the modification (haptenation or adduction) of liver proteins with aldehydes or other products of oxidative stress. This is because it has been shown that these adducted proteins can induce specific immune responses, to the adduct, the adduct plus protein (conformational antigens), as well as the unmodified parts of the protein. More importantly, it is possible to demonstrate that adducted self-proteins can induce reactivity to the normal self-protein and thereby induce autoimmune responses. Therefore, it is the purpose of this manuscript to outline the mechanism(s) by which these modified self proteins can induce autoimmune reactivity, and thus play a role in the development and/or progression of ALD.

  20. Cell therapy for autoimmune diseases

    PubMed Central

    Dazzi, Francesco; van Laar, Jacob M; Cope, Andrew; Tyndall, Alan

    2007-01-01

    Cell therapy, pioneered for the treatment of malignancies in the form of bone marrow transplantation, has subsequently been tested and successfully employed in autoimmune diseases. Autologous haemopoietic stem cell transplantation (HSCT) has become a curative option for conditions with very poor prognosis such as severe forms of scleroderma, multiple sclerosis, and lupus, in which targeted therapies have little or no effect. The refinement of the conditioning regimens has virtually eliminated transplant-related mortality, thus making HSCT a relatively safe choice. Although HSCT remains a nonspecific approach, the knowledge gained in this field has led to the identification of new avenues. In fact, it has become evident that the therapeutic efficacy of HSCT cannot merely be the consequence of a high-dose immuno-suppression, but rather the result of a resetting of the abnormal immune regulation underlying autoimmune conditions. The identification of professional and nonprofessional immunosuppressive cells and their biological properties is generating a huge interest for their clinical exploitation. Regulatory T cells, found abnormal in several autoimmune diseases, have been proposed as central to achieve long-term remissions. Mesenchymal stem cells of bone marrow origin have more recently been shown not only to be able to differentiate into multiple tissues, but also to exert a potent antiproliferative effect that results in the inhibition of immune responses and prolonged survival of haemopoietic stem cells. All of these potential resources clearly need to be investigated at the preclinical level but support a great deal of enthusiasm for cell therapy of autoimmune diseases. PMID:17367542

  1. Diet, microbiota and autoimmune diseases.

    PubMed

    Vieira, S M; Pagovich, O E; Kriegel, M A

    2014-05-01

    There is growing evidence that the commensal bacteria in the gastrointestinal tract (the gut microbiota) influence the development of autoimmunity in rodent models. Since humans have co-evolved with commensals for millennia, it is likely that people, who are genetically predisposed to autoimmunity, harbor gut microbial communities that similarly influence the onset and/or severity of disease. Beyond the current efforts to identify such disease-promoting or -preventing commensals ("pathobionts" or "symbionts"), it will be important to determine what factors modulate them. Dietary changes are known to affect both the composition and function of the gut microbial communities, which in turn can alter the innate and adaptive immune system. In this review, we focus on the relationships between diet, microbiota, and autoimmune diseases. We hypothesize that the beneficial and life-prolonging effects of caloric restriction on a variety of autoimmune models including lupus might partly be mediated by its effects on the gut microbiome and associated virome, the collection of all viruses in the gut. We give recent examples of the immunomodulatory potential of select gut commensals and their products or diet-derived metabolites in murine models of arthritis, multiple sclerosis, and type 1 diabetes. Lastly, we summarize the published phenotypes of germ-free mouse models of lupus and speculate on any role of the diet-sensitive microbiome and virome in systemic lupus and the related antiphospholipid syndrome.

  2. Juvenile autoimmune hepatitis: Spectrum of the disease

    PubMed Central

    Maggiore, Giuseppe; Nastasio, Silvia; Sciveres, Marco

    2014-01-01

    Juvenile autoimmune hepatitis (JAIH) is a progressive inflammatory liver disease, affecting mainly young girls, from infancy to late adolescence, characterized by active liver damage, as shown by high serum activity of aminotransferases, by elevated immunoglobulin G levels, high titers of serum non organ-specific and organ-specific autoantibodies, and by interface hepatitis on liver biopsy. It is a multifactorial disease of unknown etiology in which environmental factors act as a trigger in genetically predisposed individuals. Two types of JAIH are identified according to the autoantibody panel detected at diagnosis: AIH-1, characterized by the presence of anti-smooth muscle antibody and/or antinuclear antibody and AIH-2, by anti-liver-kidney microsomal antibody type 1 and/or by the presence of anti-liver cytosol type 1 antibody. Epidemiological distribution, genetic markers, clinical presentation and pattern of serum cytokines differentiate the two types of AIH suggesting possible pathogenetic mechanisms. The most effective therapy for AIH is pharmacological suppression of the immune response. Treatment should be started as soon as the diagnosis is made to avoid severe liver damage and progression of fibrosis. The aim of this review is to outline the most significant and peculiar features of JAIH, based largely on our own personal database and on a review of current literature. PMID:25067998

  3. Associated Autoimmune Diseases

    MedlinePlus

    ... only. Other helpful information is available at www.GLUTEN.net. Advances in celiac disease are fast-paced. ... should not be used to diagnose or treat gluten-related disorders or other medical conditions. For questions ...

  4. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old. PMID:22796620

  5. [Biermer's disease and autoimmune hemolytic anemia].

    PubMed

    Nafil, Hatim; Tazi, Illias; Mahmal, Lahoucine

    2012-01-01

    Biermer's disease is an autoimmune atrophic gastritis of the fundus predominantly responsible for a malabsorption of vitamin B12. Despite its association with several autoimmune disorders, few observations have reported an association with autoimmune hemolytic anemia (AIHA). We report a case of Biermer's disease associated with AIHA in a patient of 66 years old.

  6. Propylthiouracil-induced autoimmune disease.

    PubMed

    Paiaulla, Santosh; Venkategowda, Pradeep Marur; Rao, S Manimala; Balaraju, Banda

    2015-08-01

    Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. Propylthiouracil (PTU) is commonly used as first line drug in the management of hyperthyroidism. This is a case report of 24-year-old female, a known case of hyperthyroidism since 4 years, who came with a history of fever and myalgia since 3 days and dyspnea with coughing out of blood since 1 day. Patient was taking PTU (100 mg per day) since 4 years for hyperthyroidism. Patient was immediately intubated for type-II respiratory failure. Diagnosed to be having PTU-induced autoimmune disease. PTU was stopped and treated with methylprednisolone and cyclophosphamide. Clinical features improved over a period of 8 days and discharged home successfully. Having a high suspicion for the onset of autoimmune disease in hyperthyroidism patients who are on PTU therapy and timely treatment with immunosuppressants and supportive care along with the withdrawal of the drug can make a difference in morbidity and mortality. PMID:26321810

  7. Shaking Out Clues to Autoimmune Disease

    MedlinePlus

    ... of Autoimmunity-Causing T Cells Landmark Analysis Probes Nature vs. Nurture in Multiple Sclerosis Understanding Autoimmune Diseases Immune Cells Reference: Nature. 2013 Mar 6. doi: 10.1038/nature11981. [Epub ...

  8. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePlus

    ... for Updates Join Our Email List For Email Marketing you can trust. Contact AARDA National Office 22100 ... Grassroots Fundraising Workplace Giving Special Events AARDA on Facebook Copyright © 2004 - 2016. American Autoimmune Related Diseases Association, ...

  9. [Autoimmune thyroid disease and associated diseases].

    PubMed

    Lapcević, Mirjana

    2005-10-01

    Autoimmune thyroid disease (ATD) is a multifactorial, genetic disease. It is the sequelae of the impaired immunoregulation, tolerance and poor recognition of one's own proteins, oligopolysaccharides and polypeptides, due to development of somatic lymphocyte mutations. It is manifested by different clinical and morphological entities, inter-related by etiopathogenetic association, i.e., all of them are caused by disorder of immune system regulation. Chronic autoimmune thyroidism (Thyreoiditis lymphocytaria Hashimoto, HT), as well as immunogenic hyperthyroidism (Morbus Graves Basedow, MGB) are frequently associated with autoimmune diseases of other organs, such as: chronic insufficiency of salivary glands (Sy Sjögren), autoimmune hemolytic anemia, megalocytic pernicious anemia, thrombocytopenia, Rheumatoid arthritis, Diabetes mellitus (more often type 2, but also type 1), Morbus Addison, Coeliakia, and other autoimmune diseases such as systemic diseases of connecting tissue (Lupus erythematosus-SLE, Sclerodermia, Vasculitis superficialis). The incidence of autoimmune diseases has been at increase in all age groups of our population. The prevalence of organ-specific and organ-nonspecific antibodies increases with the age. Antigenicity of thyroid epithelial cell may be triggered by different chemical and biological agents (repeated viral infections), repeated stress, and in individuals with genetic propensity. Unrecognized ATD progressively leads to hypothyroidism with hyperlipidemia, blood vessel changes, osteoporosis, deformities, invalidity which substantially reduces the quality of life of patient and requires medical attention and expensive treatment on what account it is medically and socio-economically significant. Multiple diagnostic procedures contribute to faster recognition of this condition. The goal of the primary health care physician (given that preclinical phase of ATD and other associated diseases have different duration) and other specialists is to

  10. Immunomodulatory vaccines against autoimmune diseases.

    PubMed

    Sela, Michael

    2006-01-01

    Vaccines are for healthy people, to prevent them from becoming ill. Such prophylactic vaccines have been a great success. Therapeutic vaccines become more and more important, especially as life expectancy increases. Efforts to develop vaccines against such diseases as cancer, AIDS, hepatitis, tuberculosis, Alzheimer disease, and mad cow disease have not yet reached the stage where they can be successfully used on a daily basis. However, significant progress has been made in the realm of autoimmune diseases, resulting (at least in one case) in an immunomodulatory vaccine against multiple sclerosis that was developed in the author's laboratory, and that is in daily use by about 100,000 patients. The drug or therapeutic vaccine against the exacerbating-remitting type of multiple sclerosis is a copolymer of four amino acid residues, denoted Copaxone, which are related to myelin basic protein. This paper discusses Copaxone as well as a candidate immunomodulatory vaccine against myasthenia gravis, a peptide derived from the nicotinic acetylcholine receptor. Copolymer 1 (Cop 1, glatiramer acetate, Copaxone) is a synthetic amino acid random copolymer that is immunologically cross-reactive with myelin basic protein and suppresses experimental allergic encephalomyelitis in several animal species. Cop 1 slows the progression of disability and reduces the relapse rate in exacerbating-remitting multiple sclerosis patients. Cop 1 is a potent inducer of T helper 2 (Th2) regulatory cells in mice and humans; and Th2 cells are found in both the brains and spinal cords of Cop 1-treated mice and humans. MG and experimental autoimmune MG are T cell-regulated, antibody-mediated autoimmune diseases. Two peptides, representing sequences of the human AChR-alpha-subunit, p195-212 and p259-271, are immunodominant T-cell epitopes in MG patients and two strains of mice. Altered peptide ligand, composed of the randomly arranged two single amino acid analogs inhibits in vitro and in vivo MG

  11. Asialoglycoprotein receptor (ASGPR) as target autoantigen in liver autoimmunity: lost and found.

    PubMed

    Rigopoulou, Eirini I; Roggenbuck, Dirk; Smyk, Daniel S; Liaskos, Christos; Mytilinaiou, Maria G; Feist, Eugen; Conrad, Karsten; Bogdanos, Dimitrios P

    2012-12-01

    Asialoglycoprotein receptor (ASGPR) has attracted the attention of liver immunologists for many years. This liver-specific lectin was found to be a major B and T cell autoantigenic target in patients with autoimmune liver diseases, and in particular in autoimmune hepatitis (AIH). This review discusses the biological significance of ASGPR and its relevance to the pathogenesis of autoimmune and virus-triggered liver diseases. We also discuss emerging data on the diagnostic and clinical relevance of anti-ASGPR antibodies in light of recent reports based on commercially available anti-ASGPR enzyme-linked immunosorbent assays. Finally, we critically revisit the data reporting on disease-specific cellular immune responses against ASGPR and their relevance in relation to the pathogenesis of AIH.

  12. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  13. Cardiovascular Involvement in Autoimmune Diseases

    PubMed Central

    Amaya-Amaya, Jenny

    2014-01-01

    Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

  14. Involvement of Fas/FasL system in the pathogenesis of autoimmune diseases and Wilson's disease.

    PubMed

    Stassi, G; Di Felice, V; Todaro, M; Cappello, F; Zummo, G; Farina, F; Trucco, M; De Maria, R

    1999-01-01

    The interaction of Fas with FasL has been demonstrated to be implicated in the pathogenesis of several autoimmune and liver diseases. Recently, attention has been focused on the hypothesis that thyrocytes and beta cells undergo massive Fas/FasL-mediated apoptosis during autoimmune response. Similarly, hepatocyte cell death occurring following copper accumulation points towards the same mechanism.

  15. Rett syndrome: An autoimmune disease?

    PubMed

    De Felice, Claudio; Leoncini, Silvia; Signorini, Cinzia; Cortelazzo, Alessio; Rovero, Paolo; Durand, Thierry; Ciccoli, Lucia; Papini, Anna Maria; Hayek, Joussef

    2016-04-01

    Rett syndrome (RTT) is a devastating neurodevelopmental disease, previously included into the autistic spectrum disorders, affecting almost exclusively females (frequency 1:10,000). RTT leads to intellective deficit, purposeful hands use loss and late major motor impairment besides featuring breathing disorders, epilepsy and increased risk of sudden death. The condition is caused in up to 95% of the cases by mutations in the X-linked methyl-CpG binding protein 2 (MECP2) gene. Our group has shown a number of previously unrecognized features, such as systemic redox imbalance, chronic inflammatory status, respiratory bronchiolitis-associated interstitial lung disease-like lung disease, and erythrocyte morphology changes. While evidence on an intimate involvement of MeCP2 in the immune response is cumulating, we have recently shown a cytokine dysregulation in RTT. Increasing evidence on the relationship between MeCP2 and an immune dysfunction is reported, with, apparently, a link between MECP2 gene polymorphisms and autoimmune diseases, including primary Sjögren's syndrome, systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. Antineuronal (i.e., brain proteins) antibodies have been shown in RTT. Recently, high levels of anti-N-glucosylation (N-Glc) IgM serum autoantibodies [i.e., anti-CSF114(N-Glc) IgMs] have been detected by our group in a statistically significant number of RTT patients. In the current review, the Authors explore the current evidence, either in favor or against, the presence of an autoimmune component in RTT. PMID:26807990

  16. Autoimmune mechanisms in pernicious anaemia & thyroid disease.

    PubMed

    Osborne, David; Sobczyńska-Malefora, Agata

    2015-09-01

    Pernicious anaemia (PA) and some types of thyroid disease result from autoimmune processes. The autoimmune mechanisms in these conditions have not been fully elucidated. This review discusses the autoimmune mechanisms involved in PA and how these affect diagnosis and disease progression. In addition to gastric antibodies, antibodies to the vitamin B12 binding protein transcobalamin which can result in high serum B12 levels are also addressed with regard to how they affect clinical practice. The role of autoimmune susceptibility is investigated by comparing PA to one of its most common comorbidities, autoimmune thyroid disease (AITD). Thyroid disease (although not exclusively AITD) and B12 deficiency are both also implicated in the pathology of hyperhomocysteinemia, an elevated homocysteine in plasma. Since hyperhomocysteinemia is a risk factor for cardiovascular occlusive disease, this review also addresses how thyroid disease in particular leads to changes in homocysteine levels. PMID:25936607

  17. Parkinson's disease: Autoimmunity and neuroinflammation.

    PubMed

    De Virgilio, Armando; Greco, Antonio; Fabbrini, Giovanni; Inghilleri, Maurizio; Rizzo, Maria Ida; Gallo, Andrea; Conte, Michela; Rosato, Chiara; Ciniglio Appiani, Mario; de Vincentiis, Marco

    2016-10-01

    Parkinson's disease is a neurodegenerative disease that causes the death of dopaminergic neurons in the substantia nigra. The resulting dopamine deficiency in the basal ganglia leads to a movement disorder that is characterized by classical parkinsonian motor symptoms. Parkinson's disease is recognized as the most common neurodegenerative disorder after Alzheimer's disease. PD ethiopathogenesis remains to be elucidated and has been connected to genetic, environmental and immunologic conditions. The past decade has provided evidence for a significant role of the immune system in PD pathogenesis, either through inflammation or an autoimmune response. Several autoantibodies directed at antigens associated with PD pathogenesis have been identified in PD patients. This immune activation may be the cause of, rather than a response to, the observed neuronal loss. Parkinsonian motor symptoms include bradykinesia, muscular rigidity and resting tremor. The non-motor features include olfactory dysfunction, cognitive impairment, psychiatric symptoms and autonomic dysfunction. Microscopically, the specific degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies, which are brain deposits containing a substantial amount of α-synuclein, have been recognized. The progression of Parkinson's disease is characterized by a worsening of motor features; however, as the disease progresses, there is an emergence of complications related to long-term symptomatic treatment. The available therapies for Parkinson's disease only treat the symptoms of the disease. A major goal of Parkinson's disease research is the development of disease-modifying drugs that slow or stop the neurodegenerative process. Drugs that enhance the intracerebral dopamine concentrations or stimulate dopamine receptors remain the mainstay treatment for motor symptoms. Immunomodulatory therapeutic strategies aiming to attenuate PD neurodegeneration have become an attractive option and

  18. Helicobacter pylori and skin autoimmune diseases

    PubMed Central

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-01-01

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review. PMID:24587626

  19. Autoimmune thyroid disease: an expanding spectrum.

    PubMed

    Fisher, D A; Pandian, M R; Carlton, E

    1987-08-01

    Autoimmune thyroid disease classically has included Hashimoto's thyroiditis and Graves' disease. Hashimoto's thyroiditis probably also includes focal thyroiditis, fibrous thyroiditis, primary myxedema, and Hashitoxicosis as variants. Graves' disease is associated with ophthalmopathy and dermopathy, and recent evidence suggests that these manifestations are autoimmune phenomena as well. Other associated autoimmune disorders include idiopathic thrombocytopenic purpura and antigen-antibody complex nephritis. Nonthyroid endocrine autoimmune deficiency disorders also have been classified as part of the spectrum of thyroid autoimmune disease. With the recent recognition of the spectrum of autoimmune mechanisms and antibody types and methods to distinguish antibody functions or types, our understanding of postpartum and neonatal thyroid disorders has been advanced considerably. The spectrum of neonatal thyroid disorders in the infants of women with autoimmune disease relates to the levels and types of antithyroid antibodies acquired from the mother. Finally, there is suggestive evidence that nonspecific goiter, including simple adolescent goiter and multinodular goiter as well as some cases of sporadic cretinism, may be part of an even more expanded spectrum of autoimmune thyroid disease.

  20. Autoimmune diseases associated with neurofibromatosis type 1.

    PubMed

    Nanda, Arti

    2008-01-01

    Associations of autoimmune diseases with neurofibromatosis type 1 have been rarely described. In the present report, we describe two patients of neurofibromatosis type 1 having an association with vitiligo in one, and alopecia areata and autoimmune thyroiditis in another. The associations of neurofibromatosis type 1 with vitiligo, alopecia areata, and autoimmune thyroiditis have not been reported earlier. Whether these associations reflect a causal relationship with neurofibromatosis type 1 or are coincidental needs to be settled.

  1. Monogenic autoimmune diseases of the endocrine system.

    PubMed

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses.

  2. Monogenic autoimmune diseases of the endocrine system.

    PubMed

    Johnson, Matthew B; Hattersley, Andrew T; Flanagan, Sarah E

    2016-10-01

    The most common endocrine diseases, type 1 diabetes, hyperthyroidism, and hypothyroidism, are the result of autoimmunity. Clustering of autoimmune endocrinopathies can result from polygenic predisposition, or more rarely, may present as part of a wider syndrome due to a mutation within one of seven genes. These monogenic autoimmune diseases show highly variable phenotypes both within and between families with the same mutations. The average age of onset of the monogenic forms of autoimmune endocrine disease is younger than that of the common polygenic forms, and this feature combined with the manifestation of other autoimmune diseases, specific hallmark features, or both, can inform clinicians as to the relevance of genetic testing. A genetic diagnosis can guide medical management, give an insight into prognosis, inform families of recurrence risk, and facilitate prenatal diagnoses. PMID:27474216

  3. Criteria for environmentally associated autoimmune diseases.

    PubMed

    Miller, Frederick W; Pollard, K Michael; Parks, Christine G; Germolec, Dori R; Leung, Patrick S C; Selmi, Carlo; Humble, Michael C; Rose, Noel R

    2012-12-01

    Increasing evidence supports a role for the environment in the development of autoimmune diseases, as reviewed in the accompanying three papers from the National Institute of Environmental Health Sciences Expert Panel Workshop. An important unresolved issue, however, is the development of criteria for identifying autoimmune disease phenotypes for which the environment plays a causative role, herein referred to as environmentally associated autoimmune diseases. There are several different areas in which such criteria need to be developed, including: 1) identifying the necessary and sufficient data to define environmental risk factors for autoimmune diseases meeting current classification criteria; 2) establishing the existence of and criteria for new environmentally associated autoimmune disorders that do not meet current disease classification criteria; and 3) identifying in clinical practice specific environmental agents that induce autoimmune disease in individual patients. Here we discuss approaches that could be useful for developing criteria in these three areas, as well as factors that should be considered in evaluating the evidence for criteria that can distinguish individuals with such disorders from individuals without such disorders with high sensitivity and specificity. Current studies suggest that multiple lines of complementary evidence will be important and that in many cases there will be clinical, serologic, genetic, epigenetic, and/or other laboratory features that could be incorporated as criteria for environmentally associated autoimmune diseases to improve diagnosis and treatment and possibly allow for preventative strategies in the future.

  4. Human autoimmune diseases: a comprehensive update.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Gershwin, M Eric

    2015-10-01

    There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade. PMID:26212387

  5. Drug-induced liver injury with autoimmune features.

    PubMed

    deLemos, Andrew S; Foureau, David M; Jacobs, Carl; Ahrens, Will; Russo, Mark W; Bonkovsky, Herbert L

    2014-05-01

    Drug-induced liver injury (DILI) with features of autoimmunity (AI) represents an important category of hepatotoxicity due to medication exposure. Drugs repeatedly associated with AI-DILI include diclofenac, α-methyl DOPA, hydralazine, nitrofurantoin, minocycline, and more recently statins and anti-TNF-α agents. Usually, symptoms of acute liver injury occur within a few months after initiation of a culprit medication, but a longer latency period is possible. Like idiopathic autoimmune hepatitis, circulating autoantibodies and a hypergammaglobulinemia are frequently present in sera from patients with AI-DILI. If performed, a liver biopsy should demonstrate interface hepatitis with a prominent plasma cell infiltrate. The severity of AI-DILI is variable, but a complete resolution after withdrawal of the offending medication is the expectation. A response to corticosteroid therapy supports the diagnosis, whereas a lack of recurrence of symptoms or signs following corticosteroid cessation distinguishes AI-DILI from idiopathic autoimmune hepatitis.

  6. Alcohol-Related Liver Disease

    MedlinePlus

    ... to run events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community ... Liver > Liver Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn ...

  7. Coherent Somatic Mutation in Autoimmune Disease

    PubMed Central

    Ross, Kenneth Andrew

    2014-01-01

    Background Many aspects of autoimmune disease are not well understood, including the specificities of autoimmune targets, and patterns of co-morbidity and cross-heritability across diseases. Prior work has provided evidence that somatic mutation caused by gene conversion and deletion at segmentally duplicated loci is relevant to several diseases. Simple tandem repeat (STR) sequence is highly mutable, both somatically and in the germ-line, and somatic STR mutations are observed under inflammation. Results Protein-coding genes spanning STRs having markers of mutability, including germ-line variability, high total length, repeat count and/or repeat similarity, are evaluated in the context of autoimmunity. For the initiation of autoimmune disease, antigens whose autoantibodies are the first observed in a disease, termed primary autoantigens, are informative. Three primary autoantigens, thyroid peroxidase (TPO), phogrin (PTPRN2) and filaggrin (FLG), include STRs that are among the eleven longest STRs spanned by protein-coding genes. This association of primary autoantigens with long STR sequence is highly significant (). Long STRs occur within twenty genes that are associated with sixteen common autoimmune diseases and atherosclerosis. The repeat within the TTC34 gene is an outlier in terms of length and a link with systemic lupus erythematosus is proposed. Conclusions The results support the hypothesis that many autoimmune diseases are triggered by immune responses to proteins whose DNA sequence mutates somatically in a coherent, consistent fashion. Other autoimmune diseases may be caused by coherent somatic mutations in immune cells. The coherent somatic mutation hypothesis has the potential to be a comprehensive explanation for the initiation of many autoimmune diseases. PMID:24988487

  8. Environmental Exposures and Autoimmune Thyroid Disease

    PubMed Central

    2010-01-01

    Background Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease. Summary Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although ∼70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals. Conclusions Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history. PMID:20578899

  9. Allergic Disease and Autoimmune Effectors Pathways

    PubMed Central

    Rottem, Menachem; Gershwin, M. Eric; Shoenfeld, Yehuda

    2002-01-01

    Allergy and autoimmunity result from dysregulation of the immune system. Until recently, it was generally accepted that the mechanisms that govern these disease processes are quite disparate; however, new discoveries suggest possible common pathogenetic effector pathways. This review illustrates the concomitant presentation of these conditions and the potential relationship or common mechanism in some cases, by looking at the key elements that regulate the immune response in both allergic and autoimmunite conditions: mast cells, antibodies, T cells, cytokines, and genetic determinants. The parallel appearance of allergic and autoimmune conditions in the some patients may reveal that such aberrations of the immune system have a common pathophysiologic mechanism. Mast cells, which play a key role in allergic reactions, and the wealth of inflammatory mediators they express, make it likely that they have profound effects on many autoimmune processes. Activation of protein kinases by inflammatory cytokines and environmental stresses may contribute to both allergic and autoimmune diseases. The presence of autoantibodies in some allergic conditions suggests an autoimmune basis for these conditions. Because of the central role T cells play in immune reactivity, the T-cell receptor (TCR) loci have long been considered important candidates for common disease susceptibility within the immune system such as asthma, atopy, and autoimmunity. Immunomodulation is the key to a successful treatment of allergic and autoimmune conditions. PMID:12885156

  10. How pregnancy can affect autoimmune diseases progression?

    PubMed

    Piccinni, Marie-Pierre; Lombardelli, Letizia; Logiodice, Federica; Kullolli, Ornela; Parronchi, Paola; Romagnani, Sergio

    2016-01-01

    Autoimmune disorders are characterized by tissue damage, caused by self-reactivity of different effectors mechanisms of the immune system, namely antibodies and T cells. Their occurrence may be associated with genetic and/or environmental predisposition and to some extent, have implications for fertility and obstetrics. The relationship between autoimmunity and reproduction is bidirectional. This review only addresses the impact of pregnancy on autoimmune diseases and not the influence of autoimmunity on pregnancy development. Th17/Th1-type cells are aggressive and pathogenic in many autoimmune disorders and inflammatory diseases. The immunology of pregnancy underlies the role of Th2-type cytokines to maintain the tolerance of the mother towards the fetal semi-allograft. Non-specific factors, including hormonal changes, favor a switch to Th2-type cytokine profile. In pregnancy Th2, Th17/Th2 and Treg cells accumulate in the decidua but may also be present in the mother's circulation and can regulate autoimmune responses influencing the progression of autoimmune diseases. PMID:27651750

  11. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    Autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before pregnancy, during pregnancy, and in the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy.

  12. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    Autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before pregnancy, during pregnancy, and in the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  13. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-12-31

    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  14. Autoimmune hepatitis.

    PubMed

    Roberts, E A

    1995-01-01

    Autoimmune hepatitis can present as either acute or chronic disease in children. Clinical and laboratory features, including association with extrahepatic autoimmune syndromes and prompt response to immunosuppressive treatment, circulating autoantibodies and hypergammaglobulinemia, suggest an immune etiology. However, the disease mechanism remains uncertain. Different types of autoimmune hepatitis are defined on the basis of which autoantibodies are present: anti-smooth muscle (type 1), anti-liver/kidney microsomal (type 2), or anti-soluble liver antigen (type 3). Diseases which may be clinically similar to autoimmune hepatitis must be excluded before the diagnosis of autoimmune hepatitis is established: Wilson's disease, primary sclerosing cholangitis, chronic hepatitis B or C, and drug-induced liver disease are among the most important entities. Corticosteroids alone or with azathioprine constitute the usual treatment for autoimmune hepatitis. Although some children achieve a complete remission, or even recovery, and can stop immunosuppressive treatment, others required low-dose prednisone treatment indefinitely.

  15. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

  16. Autism and Autoimmune Disease: A Family Study

    ERIC Educational Resources Information Center

    Money, John; And Others

    1971-01-01

    Described in a family in which the youngest boy has early infantile autism, Addison's disease, and moniliasis and two older boys have autoimmune disease with hypoparathyroidism, Addison's disease, moniliasis, and either alopecia totalis or diabetes mellitus, while the oldest boy and parents are symptom free. (KW)

  17. Extracellular Matrix and Liver Disease

    PubMed Central

    Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

    2014-01-01

    Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

  18. [Glycosylation of autoantibodies in autoimmunes diseases].

    PubMed

    Goulabchand, R; Batteux, F; Guilpain, P

    2013-12-01

    Protein glycosylation is one of the most common post-translational modifications, involved in the well described protein biosynthesis process. Protein glycosylation seems to play a major role in the pathogenesis of auto-immune diseases. Herein are described the main alterations of autoantibody glycosylation associated with autoimmunes diseases such as rheumatoid arthritis, IgA glomerulonephritis, Schoenlein-Henoch purpura, Sjögren's syndrome, systemic scleroderma, systemic lupus erythematosus, myasthenia gravis and granulomatosis with polyangiitis (Wegener). Molecular identification of altered immunoglobulin glycosylation could lead to a better understanding of the pathogenesis of those diseases, might allow an evaluation of their biological activity and could even be a new therapeutic target.

  19. Autoimmune hepatitis

    MedlinePlus

    Lupoid hepatitis; Chronic acute liver disease ... This form of hepatitis is an autoimmune disease . The body's immune system cannot tell the difference between healthy body tissue and harmful, outside ...

  20. Polyglandular autoimmune diseases in a dermatological clinical setting: vitiligo-associated autoimmune diseases.

    PubMed

    Amerio, Paolo; Di Rollo, Daniela; Carbone, Angelo; Auriemma, Matteo; Marra, Maria Elena; De Remigis, Pierluigi; Feliciani, Claudio; Tracanna, Marco; Tulli, Antonio

    2010-01-01

    Vitiligo is an acquired hypomelanotic disorder characterized by depigmented macules resulting from the loss of functional melanocytes. Many different etiological hypotheses have been suggested for vitiligo, the most recent of which involves a combination of interacting environmental and genetic factors. Among the various pieces of evidence in support of an autoimmune origin of vitiligo, there is the epidemiological association with several autoimmune diseases. The most frequently reported association is with autoimmune thyroiditis; however, other diseases such as rheumatoid arthritis, diabetes mellitus, pernicious anemia and chronic urticaria have been described in variable percentages, depending upon the genetics of the population studied. Among the diseases described in association with vitiligo there are the so-called autoimmune polyglandular syndromes (APS). Here we report 31 cases of APS diagnosed in 113 vitiligo patients, according to the newest classification. Autoimmune association was more present in generalized non segmental vitiligo and was more frequent in females. The most frequent association was with thyroid autoimmune disease, followed by autoimmune gastritis and alopecia areata. ANA positivity was similar to that reported previously in the general population. We stress the importance of an assessment for autoimmune diseases in vitiligo patients. PMID:20395193

  1. Recent Advances in Autoimmune Thyroid Diseases

    PubMed Central

    Yoo, Won Sang

    2016-01-01

    Autoimmune thyroid disease (AITD) includes hyperthyroid Graves disease, hypothyroid autoimmune thyroiditis, and subtle subclinical thyroid dysfunctions. AITD is caused by interactions between genetic and environmental predisposing factors and results in autoimmune deterioration. Data on polymorphisms in the AITD susceptibility genes, related environmental factors, and dysregulation of autoimmune processes have accumulated over time. Over the last decade, there has been progress in the clinical field of AITD with respect to the available diagnostic and therapeutic methods as well as clinical consensus. The updated clinical guidelines allow practitioners to identify the most reasonable and current approaches for proper management. In this review, we focus on recent advances in understanding the genetic and environmental pathogenic mechanisms underlying AITD and introduce the updated set of clinical guidelines for AITD management. We also discuss other aspects of the disease such as management of subclinical thyroid dysfunction, use of levothyroxine plus levotriiodothyronine in the treatment of autoimmune hypothyroidism, risk assessment of long-standing antithyroid drug therapy in recurrent Graves' hyperthyroidism, and future research needs. PMID:27586448

  2. Autoimmune thyroid disease and chronic urticaria.

    PubMed

    Monge, Cecilia; Demarco, Paul; Burman, Kenneth D; Wartofsky, Leonard

    2007-09-01

    We report six cases of autoimmune thyroid disease associated with chronic urticaria and briefly review the literature, including the histopathological nature of such lesions, and their aetiology and pathogenesis. In view of the prevalence of thyroid disease in patients with chronic urticaria, screening measurements of thyrotropin and anti-thyroperoxidase antibodies are recommended, although negative antibodies do not exclude a relationship between urticaria and thyroid autoimmunity. After failure of conventional therapy for urticaria, patients who are apparently clinically euthyroid may be considered for a trial with levothyroxine. Improvement of urticaria was seen with levothyroxine treatment in three of four patients with only marginal abnormalities in thyroid function.

  3. Coffee and Liver Disease.

    PubMed

    Wadhawan, Manav; Anand, Anil C

    2016-03-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895

  4. Prevalence of Sjögren's syndrome in autoimmune diseases.

    PubMed Central

    Coll, J; Rives, A; Griñó, M C; Setoain, J; Vivancos, J; Balcells, A

    1987-01-01

    Investigations were carried out in 122 patients in order to identify features of Sjögren's syndrome (keratoconjunctivitis sicca and xerostomia). There were 78 patients with autoimmune diseases (rheumatoid arthritis 21, scleroderma 16, sicca syndrome 16, primary biliary cirrhosis 14, and other autoimmune disorders 11), 11 patients with chronic liver disease other than primary biliary cirrhosis, and 33 patients with a variety of non-autoimmune conditions or no obvious disease. Keratoconjunctivitis sicca was diagnosed by Schirmer's test and rose bengal staining. The oral component was diagnosed by labial biopsy and salivary scintigraphy. Forty nine patients had a definite Sjögren's syndrome, and 77 patients had the syndrome definitely or probably. Definite Sjögren's syndrome occurred in 62% of patients with rheumatoid arthritis, in 69% of patients with scleroderma, and in 71% of patients with primary biliary cirrhosis. Sjögren's syndrome was not present in any of the patients with non-autoimmune conditions. These results show that in an unselected group of patients with Sjögren's syndrome the prevalence of rheumatoid arthritis (26%), scleroderma (22%), sicca syndrome (22%), and primary biliary cirrhosis (20%) is similar. Also the occurrence of Sjögren's syndrome in primary biliary cirrhosis is even higher than that in rheumatoid arthritis. PMID:3592784

  5. Hepatitis B virus (HBV) and autoimmune disease.

    PubMed

    Maya, Ram; Gershwin, M Eric; Shoenfeld, Yehuda

    2008-02-01

    The etiology and pathogenesis of autoimmune diseases have long been an enigmatic subject that have involved genetic and environmental factors. Recent intriguing data has contributed to the mechanisms involved, including the relationship of infectious agents and loss of tolerance. This loss of tolerance is illustrated by the data on the immune response to Hepatitis B virus such as the molecular mimicry between HBV antigens and self proteins, the generation of immune complexes between HBV antigens and antibodies, and apoptosis/tissue damage resulting in the exposure of intracellular antigens to the immune system. In this paper, we review the current database related to HBV infection and a variety of autoimmune conditions, including autoimmune hepatitis, systemic lupus erythematosus, aplastic anemia, antiphospholipid syndrome, polyarteritis nodosa, rheumatoid arthritis, type 1 diabetes, multiple sclerosis, thyroid disease and uveitis. PMID:18270862

  6. Scurfy mice: A model for autoimmune disease

    SciTech Connect

    Godfrey, V.L.

    1993-01-01

    Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.

  7. Coeliac disease and autoimmune disease-genetic overlap and screening.

    PubMed

    Lundin, Knut E A; Wijmenga, Cisca

    2015-09-01

    Coeliac disease is a treatable, gluten-induced disease that often occurs concurrently with other autoimmune diseases. In genetic studies since 2007, a partial genetic overlap between these diseases has been revealed and further insights into the pathophysiology of coeliac disease and autoimmunity have been gained. However, genetic screening is not sensitive and specific enough to accurately predict disease development. The current method to diagnose individuals with coeliac disease is serological testing for the presence of autoantibodies whilst the patient is on a regular, gluten-containing diet, followed by gastroduodenoscopy with duodenal biopsy. Serological test results can also predict the probability of coeliac disease development, even if asymptomatic. In patients with autoimmune diseases known to occur alongside coeliac disease (particularly type 1 diabetes mellitus or thyroid disorders), disease screening-and subsequent treatment if coeliac disease is detected-could have beneficial effects on progression or potential complications of both diseases, owing to the effectiveness of gluten-free dietary interventions in coeliac disease. However, whether diagnosis of coeliac disease and subsequent dietary treatment can prevent autoimmune diseases is debated. In this Review, the genetic and immunological features of coeliac disease, overlap with other autoimmune diseases and implications for current screening strategies will be discussed.

  8. Is hypertension an autoimmune disease?

    PubMed Central

    Pober, Jordan S.

    2014-01-01

    T cells are required for significant blood pressure elevation in mouse models of hypertension. Recent evidence suggests that the treatments that raise blood pressure in these animal models also cause oxidation within DCs, resulting in formation of isoketal adducts of self-proteins, which activate antigen-presenting functions of these cells and serve as a source of modified self-antigens. T cells specific for these modified self-antigens then produce cytokines that promote blood pressure elevation, consistent with the idea that hypertension is an autoimmune response to altered self. Here, I will review the new evidence for this idea put forth by Kirabo and colleagues in this issue of the JCI, identify a number of as yet unanswered questions, and discuss some of the therapeutic implications. PMID:25244091

  9. Aging and liver disease

    PubMed Central

    Kim, Hee; Kisseleva, Tatiana; Brenner, David A.

    2016-01-01

    Purpose of review Aging is a condition in which a person gradually loses the ability to maintain homeostasis, due to structural alteration or dysfunction. Aging is a major risk factor for most chronic diseases. As the liver has a remarkable ability to regenerate, this review assessed the effect of aging on clinical liver disease with references to preclinical models when relevant to pathogenesis. Recent findings Aging has been shown to not only enhance vulnerability to acute liver injury but also increase susceptibility of the fibrotic response. Aging is associated with the severity and poor prognosis of various liver diseases including nonalcoholic fatty liver disease, alcoholic liver disease, hepatitis C, and liver transplantation. Summary Treatment of older patients with liver disease may require different or longer interventions. Transplantation of an older liver will be less tolerant of subsequent injury. Future studies are needed to understand more about the molecular mechanism of aging and contribute to the development of a noble treatment strategy that can block the progression of aging-induced liver diseases. PMID:25850346

  10. Autoimmune Hepatitis Induced by Syngeneic Liver Cytosolic Proteins Biotransformed by Alcohol Metabolites

    PubMed Central

    Thiele, Geoffrey M.; Duryee, Michael J.; Willis, Monte S.; Tuma, Dean J.; Radio, Stanley J.; Hunter, Carlos D.; Schaffert, Courtney S.; Klassen, Lynell W.

    2010-01-01

    Background & Aims Aldehydes that are produced following the breakdown of ethanol (acetaldehyde) and lipid peroxidation of membranes (malondialdehyde) have been shown to bind (adduct) proteins. Additionally, these two aldehydes can combine (MAA) on non-syngeneic and syngeneic proteins to initiate numerous immune responses to the unmodified part of the protein in the absence of an adjuvant. Therefore, these studies provide a potential mechanism for the development of antigen-specific immune responses resulting in liver damage should syngeneic liver proteins be adducted with MAA. Methods This study sought to test whether MAA modified syngeneic liver cytosolic proteins administered daily in the absence of adjuvant into C57BL/6 mice abrogates tolerance to initiate a MAA induced autoimmune-like hepatitis (MIAH). Results In mice immunized with MAA modified cytosols there was an increase in liver damage as assessed by AST/ALT levels that correlated with liver pathology scores and the presence of the pro-fibrotic factors; smooth muscle actin (SMA), TGF-β, and collagen. IgG antibodies and T-cell proliferative responses specific for cytosolic proteins were also detected. Pro-inflammatory cytokines were produced in the livers of animals exposed to MAA-modified cytosols. Finally, transfer of immunized T-cells to naïve animals caused biochemical and histological evidence of liver damage. Conclusions These data demonstrate that a disease with an autoimmune-like pathophysiology can be generated in this animal model using soluble MAA modified syngeneic liver cytosols as the immunogen. These studies provide insight into potential mechanism(s) that the metabolites of alcohol may play in contributing to the onset of an autoimmune-like disease in ALD patients. PMID:20860619

  11. Anti-cytokine autoantibodies in autoimmune diseases

    PubMed Central

    Cappellano, Giuseppe; Orilieri, Elisabetta; Woldetsadik, Abiy D; Boggio, Elena; Soluri, Maria F; Comi, Cristoforo; Sblattero, Daniele; Chiocchetti, Annalisa; Dianzani, Umberto

    2012-01-01

    An overview of the current literature is showing that autoantibodies (AutoAbs) against cytokines are produced in several pathological conditions, including autoimmune diseases, but can also be detected in healthy individuals. In autoimmune diseases, these AutoAbs may also be prognostic markers, either negative (such as AutoAbs to IL-8 and IL-1α in rheumatoid arthritis) or positive (such as AutoAbs to IL-6 in systemic sclerosis and those to osteopontin in rheumatoid arthritis). They may have neutralizing activity and influence the course of the physiological and pathological immune responses. High levels of AutoAbs against cytokines may even lead to immunodeficiency, such as those to IL-17 in autoimmune polyendocrine syndrome type I or those to IFN-γ in mycobacterial infections. Their role in human therapy may be exploited not only through passive immunization but also through vaccination, which may improve the costs for long lasting treatments of autoimmune diseases. Detection and quantification of these AutoAbs can be profoundly influenced by the technique used and standardization of these methods is needed to increase the value of their analysis. PMID:23885320

  12. Autoimmune Pathogenesis of Chagas Heart Disease

    PubMed Central

    Bonney, Kevin M.; Engman, David M.

    2016-01-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors—autoimmunity—has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. PMID:25857229

  13. Immunosuppressive Therapy in Immune-Mediated Liver Disease in the Non-Transplanted Patient

    PubMed Central

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  14. Immunosuppressive therapy in immune-mediated liver disease in the non-transplanted patient.

    PubMed

    Abhyankar, Anita; Tapper, Elliot; Bonder, Alan

    2013-01-01

    Autoimmune liver disease management goals are primarily slowing disease progression and symptomatic treatment. There are few options for curative medical management other than transplant for a spectrum of autoimmune liver disease that encompasses autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis as well as their overlap syndromes. These diseases are managed primarily with immunosuppressive therapy. Herein, we review the current literature, detailing the promise and pitfalls of the recommended immunosuppressive therapy for these challenging diseases. PMID:24380894

  15. Imaging combined autoimmune and infectious disease microarrays

    NASA Astrophysics Data System (ADS)

    Ewart, Tom; Raha, Sandeep; Kus, Dorothy; Tarnopolsky, Mark

    2006-09-01

    Bacterial and viral pathogens are implicated in many severe autoimmune diseases, acting through such mechanisms as molecular mimicry, and superantigen activation of T-cells. For example, Helicobacter pylori, well known cause of stomach ulcers and cancers, is also identified in ischaemic heart disease (mimicry of heat shock protein 65), autoimmune pancreatitis, systemic sclerosis, autoimmune thyroiditis (HLA DRB1*0301 allele susceptibility), and Crohn's disease. Successful antibiotic eradication of H.pylori often accompanies their remission. Yet current diagnostic devices, and test-limiting cost containment, impede recognition of the linkage, delaying both diagnosis and therapeutic intervention until the chronic debilitating stage. We designed a 15 minute low cost 39 antigen microarray assay, combining autoimmune, viral and bacterial antigens1. This enables point-of-care serodiagnosis and cost-effective narrowly targeted concurrent antibiotic and monoclonal anti-T-cell and anti-cytokine immunotherapy. Arrays of 26 pathogen and 13 autoimmune antigens with IgG and IgM dilution series were printed in triplicate on epoxysilane covalent binding slides with Teflon well masks. Sera diluted 1:20 were incubated 10 minutes, washed off, anti-IgG-Cy3 (green) and anti-IgM-Dy647 (red) were incubated for 5 minutes, washed off and the slide was read in an ArrayWoRx(e) scanning CCD imager (Applied Precision, Issaquah, WA). As a preliminary model for the combined infectious disease-autoimmune diagnostic microarray we surveyed 98 unidentified, outdated sera that were discarded after Hepatitis B antibody testing. In these, significant IgG or IgM autoantibody levels were found: dsDNA 5, ssDNA 11, Ro 2, RNP 7, SSB 4, gliadin 2, thyroglobulin 13 cases. Since control sera showed no autoantibodies, the high frequency of anti-DNA and anti-thyroglobulin antibodies found in infected sera lend increased support for linkage of infection to subsequent autoimmune disease. Expansion of the antigen

  16. Complicating autoimmune diseases in myasthenia gravis: a review.

    PubMed

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis.

  17. Complicating autoimmune diseases in myasthenia gravis: a review

    PubMed Central

    Nacu, Aliona; Andersen, Jintana Bunpan; Lisnic, Vitalie; Owe, Jone Furlund; Gilhus, Nils Erik

    2015-01-01

    Abstract Myasthenia gravis (MG) is a rare autoimmune disease of skeletal muscle endplates. MG subgroup is relevant for comorbidity, but usually not accounted for. MG patients have an increased risk for complicating autoimmune diseases, most commonly autoimmune thyroid disease, systemic lupus erythematosus and rheumatoid arthritis. In this review, we present concomitant autoimmune disorders associated with the different MG subgroups, and show how this influences treatment and prognosis. Concomitant MG should always be considered in patients with an autoimmune disorder and developing new neuromuscular weakness, fatigue or respiratory failure. When a second autoimmune disorder is suspected, MG should be included as a differential diagnosis. PMID:25915571

  18. Prenatal immunotoxicant exposure and postnatal autoimmune disease.

    PubMed Central

    Holladay, S D

    1999-01-01

    Reports in humans and rodents indicate that immune development may be altered following perinatal exposure to immunotoxic compounds, including chemotherapeutics, corticosteroids, polycyclic hydrocarbons, and polyhalogenated hydrocarbons. Effects from such exposure may be more dramatic or persistent than following exposure during adult life. For example, prenatal exposure to the insecticide chlordane or to the polycyclic aromatic hydrocarbon benzo[(italic)a(/italic)]pyrene produces what appears to be lifelong immunosuppression in mice. Whether prenatal immunotoxicant exposure may predispose the organism to postnatal autoimmune disease remains largely unknown. In this regard, the therapeutic immunosuppressant cyclosporin A (CsA) crosses the placenta poorly. However, lethally irradiated rodents exposed to CsA postsyngeneic bone marrow transplant (i.e., during re-establishment of the immune system) develop T-cell-mediated autoimmune disease, suggesting this drug may produce a fundamental disruption in development of self-tolerance by T cells. The environmental contaminant 2,3,7, 8-tetrachlorodibenzo-(italic)p(/italic)-dioxin (TCDD) crosses the placenta and produces fetal thymic effects (italic)in vivo(/italic) similar to effects of CsA in fetal thymic organ culture, including inhibited thymocyte maturation and reduced expression of thymic major histocompatability complex class II molecules. These observations led to the suggestion that gestational exposure to TCDD may interfere with normal development of self-tolerance. Possibly supporting this hypothesis, when mice predisposed to development of autoimmune disease were treated with TCDD during gestation, postnatal autoimmunity was exacerbated. Similar results have been reported for mice exposed to diethylstilbestrol during development. These reports suggest that prenatal exposure to certain immunotoxicants may play a role in postnatal expression of autoimmunity. PMID:10502532

  19. Roles of A20 in autoimmune diseases.

    PubMed

    Zhang, Min; Peng, Ling-Long; Wang, Ying; Wang, Jian-Shu; Liu, Jiao; Liu, Meng-Meng; Hu, Jia; Song, Bin; Yang, Hai-Bing

    2016-04-01

    A20 (TNFAIP3), known to inhibit NF-κB function by deubiquitinating-specific NF-κB signaling molecules, has been found in many cell types of the immune system. Recent findings suggest that A20 is essential for the development and functional performance of dendritic cell, B cell, T cell and macrophage. A number of studies further demonstrate that these cells are crucial in the pathogenesis of autoimmune diseases, such as type 1 diabetes, systemic lupus erythematosus, inflammatory bowel disease, ankylosing arthritis, Sjögren's syndrome and rheumatoid arthritis. In this article, we focus on the recent advances on the roles of A20 in autoimmune diseases and discuss the therapeutic significance of these new findings. PMID:26135958

  20. Avian models with spontaneous autoimmune diseases

    PubMed Central

    Wick, Georg; Andersson, Leif; Hala, Karel; Gershwin, M. Eric; Selmi, Carlo F.; Erf, Gisela F.; Lamont, Susan J.; Sgonc, Roswitha

    2012-01-01

    Autoimmune diseases in human patients only become clinically manifest when the disease process has developed to a stage where functional compensation by the afflicted organ or system is not possible any more. In order to understand the initial etiologic and pathogenic events that are generally not yet accessible in humans, appropriate animal models are required. In this respect, spontaneously developing models - albeit rare – reflect the situation in humans much more closely than experimentally induced models, including knockout and transgenic mice. The present review describes three spontaneous chicken models for human autoimmune diseases, the Obese strain (OS) with a Hashimoto-like autoimmune thyroiditis, the University of California at Davis lines 200 and 206 (UCD-200 and 206) with a scleroderma-like disease and the amelanotic Smyth line with a vitiligo-like syndrome (SLV). Special emphasis is given to the new opportunities to unravel the genetic basis of these diseases in view of the recently completed sequencing of the chicken genome. PMID:17145302

  1. Achalasia and thyroid disease: possible autoimmune connection?

    PubMed

    Quidute, Ana Rosa P; Freitas, Eduardo Vasconcelos de; Lima, Tadeu Gonçalves de; Feitosa, Ana Márcia Lima; Santos, Joyce Paiva dos; Correia, José Walter

    2012-12-01

    Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. PMID:23329193

  2. Autoimmune Inner Ear Disease (AIED)

    MedlinePlus

    ... Other Topics Military Resources Infographics & Presentations Videos Paid Advertisement Meniere's Disease SPC-Flakes have been clinically shown ... Mention “VEDA” to receive a 15% discount. Paid Advertisement Disclaimer Information on this website is not intended ...

  3. Oral Tolerance: Therapeutic Implications for Autoimmune Diseases

    PubMed Central

    Faria, Ana M. C.; Weiner, Howard L.

    2006-01-01

    Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy. PMID:17162357

  4. [Regulatory B cells in human autoimmune diseases].

    PubMed

    Miyagaki, Tomomitsu

    2015-01-01

    B cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in clinical research using human samples. PMID:26725860

  5. [Vaccinations in patients with autoimmune diseases].

    PubMed

    Bühler, Silja; Hatz, Christoph

    2016-01-01

    The number of individuals with autoimmune diseases treated with immunosuppressive drugs is increasing steadily. The variety of immunosuppressive drugs and in particular biological therapies is also rising. The autoimmune disease itself as well as the immunosuppressive therapy increases the risk of infection in this population. Particularly the risk of vaccine-preventable infections is elevated. Thus, preventing infections by the means of vaccination is of utmost importance. The Division of Infectious Diseases of the Epidemiology, Biostatistics and Prevention Institute, University of Zurich, performed a literature search on the topic of vaccinations in patients with autoimmune diseases upon request by the Swiss Federal Commission for Vaccination Issues. Overall, data are scarce. The following main points were retrieved from the literature: Inactivated vaccines are safe, but their immunogenicity may be reduced under immunosuppressive therapy. In addition to the generally recommended basic vaccinations, specific vaccinations, such as influenza and pneumococcal vaccination are indicated in these patient groups. Live vaccines are generally contraindicated under immunosuppressive therapy due to safety concerns. However, specific exceptions apply. Furthermore, certain time intervals for the administration of live vaccines after pausing or ceasing an immunosuppressive therapy should be respected. PMID:27268452

  6. Autoimmune hepatitis.

    PubMed

    Heneghan, Michael A; Yeoman, Andrew D; Verma, Sumita; Smith, Alastair D; Longhi, Maria Serena

    2013-10-26

    Autoimmune hepatitis is a disease of the hepatic parenchyma that can present in acute or chronic forms. In common with many autoimmune diseases, autoimmune hepatitis is associated with non-organ-specific antibodies in the context of hepatic autoimmunity. This dichotomy has made definition of a unifying hypothesis in the pathophysiology of the disease difficult, although data from the past 8 years have drawn attention to the role of regulatory T cells. Several triggers have been identified, and the disease arises in genetically susceptible individuals. Clinical and biochemical remission is achievable in up to 85% of cases. For the remaining patients, alternative immunosuppression strategies are an option. Liver transplantation provides an excellent outcome for patients with acute liver failure or complications of end-stage liver disease, including hepatocellular carcinoma. Variant or overlapping syndromes are worthy of consideration when unexpected disease features arise.

  7. Autoimmune disease and epigenome regulation.

    PubMed

    Fujio, Keishi

    2016-01-01

      Epigenetic modifications play a central role in the cellular programming of gene expression. Two of the most characterized epigenetic modifications are DNA methylation and histone modification. Recent observation that a number of GWAS SNP for immunological diseases localize to immune enhancers suggests the importance of epigenetic modifications that control enhancer activity. Epigenome-wide analysis of DNA-methylation in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) revealed differential DNA methylation in a number of disease-related gene pathways. With regard to histone mark, the requirement of millions of cells for established protocol prevents application to clinical samples. However, recent technical advances enable us to capture open chromatin in small amount of patient samples. As epigenetic modifications function as an integrator of environmental stimulation and the underlying genetic variant, detailed epigenetic analysis combined with genetic and environmental factors may facilitate the understanding of the progression of human immunological diseases. PMID:27181231

  8. Evaluation of autoimmune thyroid disease in melasma.

    PubMed

    Rostami Mogaddam, Majid; Iranparvar Alamdari, Manouchehr; Maleki, Nasrollah; Safavi Ardabili, Nastaran; Abedkouhi, Selma

    2015-06-01

    Melasma is one of the most frequently acquired hyperpigmentation disorders clinically characterized by symmetrical brown patches on sun-exposed areas. To date, few studies have been conducted about the relationship between thyroid autoimmun-ity and melasma. To evaluate the thyroid dysfunction and autoimmunity in nonpregnant women with melasma. A total of 70 women with melasma and 70 age-matched healthy women with no history of melasma were enrolled in the study. We studied the thyroid hormone profile in both groups. The statistical analysis was performed using SPSS software. Patients with melasma had 18.5% frequency of thyroid disorders, and 15.7% had positive anti-TPO, while subjects from the control group had a 4.3% frequency of thyroid abnormalities, and only 5.7% had positive anti-TPO. There was a significantly higher prevalence of thyroid dysfunction in women with melasma compared with control group (P = 0.008). This study suggests that there is a relationship between thyroid autoimmunity and melasma. However, to make recommendations on screening for thyroid disease in patients with melasma, future research of good methodological quality is needed.

  9. [Relation between autoimmune thyroid diseases and connective tissue diseases].

    PubMed

    Barragán-Garfias, Jorge Alberto; Zárate, Arturo

    2013-01-01

    The main physiological function of the immune system consists in the defense against infectious micro-organisms. Sometimes there is a loss of immunological tolerance with the consequence of ignorance of self-antibodies. Some thyroid diseases are related to autoimmune diseases associated with the most common exocrine glands between them. There are also the autoimmune thyroid organ specific diseases, such as Graves-Basedow and the Hashimoto thyroiditis. It has been shown that there is a higher prevalence of autoimmune thyroid diseases in patients with connective tissue diseases (systemic autoimmune) such as Sjögren syndrome, rheumatoid arthritis, systemic lupus erithmatosis and systemic myopathic diseases. In the same way a higher prevalence of antinuclear antibodies against antigens extracted from the nucleus in patients with a thyroid autoimmune disease has been identified. There is a high percentage of patients with subclinical thyroid diseases, and it is recommended for patients with connective tissue diseases with hypo- or hyperthyroidism to have thyroid globulin and peroxide antibodies measured.

  10. Secondary autoimmune diseases occurring after HSCT for an autoimmune disease: a retrospective study of the EBMT Autoimmune Disease Working Party.

    PubMed

    Daikeler, Thomas; Labopin, Myriam; Di Gioia, Massimo; Abinun, Mario; Alexander, Tobias; Miniati, Irene; Gualandi, Francesca; Fassas, Athanasios; Martin, Thierry; Schwarze, Carl Philipp; Wulffraat, Nico; Buch, Maya; Sampol, Antonia; Carreras, Enric; Dubois, Benedicte; Gruhn, Bernd; Güngör, Tayfun; Pohlreich, David; Schuerwegh, Annemie; Snarski, Emilian; Snowden, John; Veys, Paul; Fasth, Anders; Lenhoff, Stig; Messina, Chiara; Voswinkel, Jan; Badoglio, Manuela; Henes, Jörg; Launay, David; Tyndall, Alan; Gluckman, Eliane; Farge, Dominique

    2011-08-11

    To specify the incidence and risk factors for secondary autoimmune diseases (ADs) after HSCT for a primary AD, we retrospectively analyzed AD patients treated by HSCT reported to EBMT from 1995 to 2009 with at least 1 secondary AD (cases) and those without (controls). After autologous HSCT, 29 of 347 patients developed at least 1 secondary AD within 21.9 (0.6-49) months and after allogeneic HSCT, 3 of 16 patients. The observed secondary ADs included: autoimmune hemolytic anemia (n = 3), acquired hemophilia (n = 3), autoimmune thrombocytopenia (n = 3), antiphospholipid syndrome (n = 2), thyroiditis (n = 12), blocking thyroid-stimulating hormone receptor antibody (n = 1), Graves disease (n = 2), myasthenia gravis (n = 1), rheumatoid arthritis (n = 2), sarcoidosis (n = 2), vasculitis (n = 1), psoriasis (n = 1), and psoriatic arthritis (n = 1). After autologous HSCT for primary AD, the cumulative incidence of secondary AD was 9.8% ± 2% at 5 years. Lupus erythematosus as primary AD, and antithymocyte globulin use plus CD34(+) graft selection were important risk factors for secondary AD by multivariate analysis. With a median follow-up of 6.2 (0.54-11) years after autologous HSCT, 26 of 29 patients with secondary AD were alive, 2 died during their secondary AD (antiphospholipid syndrome, hemophilia), and 1 death was HSCT-related. This European multicenter study underlines the need for careful management and follow-up for secondary AD after HSCT.

  11. Animal models of chronic liver diseases.

    PubMed

    Liu, Yan; Meyer, Christoph; Xu, Chengfu; Weng, Honglei; Hellerbrand, Claus; ten Dijke, Peter; Dooley, Steven

    2013-03-01

    Chronic liver diseases are frequent and potentially life threatening for humans. The underlying etiologies are diverse, ranging from viral infections, autoimmune disorders, and intoxications (including alcohol abuse) to imbalanced diets. Although at early stages of disease the liver regenerates in the absence of the insult, advanced stages cannot be healed and may require organ transplantation. A better understanding of underlying mechanisms is mandatory for the design of new drugs to be used in clinic. Therefore, rodent models are being developed to mimic human liver disease. However, no model to date can completely recapitulate the "corresponding" human disorder. Limiting factors are the time frame required in humans to establish a certain liver disease and the fact that rodents possess a distinct immune system compared with humans and have different metabolic rates affecting liver homeostasis. These features account for the difficulties in developing adequate rodent models for studying disease progression and for testing new pharmaceuticals to be translated into the clinic. Nevertheless, traditional and new promising animal models that mimic certain attributes of chronic liver diseases are established and being used to deepen our understanding in the underlying mechanisms of distinct liver diseases. This review aims at providing a comprehensive overview of recent advances in animal models recapitulating different features and etiologies of human liver diseases. PMID:23275613

  12. Nutrition and liver diseases.

    PubMed

    Teran, J C

    1999-08-01

    Malnutrition and micronutrient deficiencies are common in patients with liver diseases. The pathogenesis of protein-energy malnutrition in cirrhosis involves many factors, including poor oral intake, malabsorption, and metabolic abnormalities similar to stress. Encephalopathy may complicate cirrhosis but is usually not caused by diet. Protein restriction is only necessary in rare patients with refractory encephalopathy. The use of branched-chain amino-acid solutions is not supported by the literature. Chronic liver diseases without cirrhosis are not usually associated with protein-energy malnutrition, but vitamin and mineral deficiencies are common, especially with significant cholestasis. Fatty liver may result from excessive triglyceride uptake and production by the liver or by a secretory defect. Therapy for fatty liver depends on its cause. Chronic total parenteral nutrition may induce fatty liver and inflammation especially in patients with short-bowel syndrome. Deficiency of choline in parenteral nutrition has been proposed as the mechanism for liver disease. Acute liver diseases such as fulminant hepatic failure or alcoholic hepatitis are considered hypercatabolic diseases and thus require prompt nutritional intervention with a high-calorie enteral or parenteral formula. In fulminant hepatic failure, low-protein, fluid-restricted formulas are recommended. PMID:10980970

  13. The importance of liver microcirculation in promoting autoimmune hepatitis via maintaining an inflammatory cytokine milieu--a mathematical model study.

    PubMed

    Lettmann, Karsten Alexander; Hardtke-Wolenski, Matthias

    2014-05-01

    In autoimmune diseases, inflammatory cytokine concentrations are important for initiating and maintaining the status of autoimmunity. Autoimmune hepatitis (AIH) is an inflammatory liver disease characterized by a loss of immune tolerance against specific antigens located in hepatocytes. During the progression of the disease, antigen-presenting cells and different classes of T-helper cells secrete specific cytokines important for maintaining the disease. As these cytokines are secreted into the local liver environment, the blood flow in liver sinusoids might influence the local cytokine concentration. Considering the liver tissue as a porous medium, based on Darcy׳s law, the microcirculation within a liver lobule was modelled. Using realistic physiological pressure differences and tissue permeabilities, the blood velocity inside the sinusoids could be calculated and validated with blood velocity data obtained via Orthogonal Polarization Spectral Imaging (OPSI). Furthermore, oxygen consumption is modelled to obtain Rappaport׳s acinus model. Finally, steady state spatial distributions of secreted cytokines within the liver lobule could be estimated for specified realistic production rates of T-helper cells. It could be demonstrated that the characteristics of the liver microcirculation have an important impact on establishing inflammatory cytokine levels within the portal fields and the vascular septa promoting the occurrence of interface hepatitis.

  14. Chronic liver disease in Aboriginal North Americans

    PubMed Central

    Scott, John D; Garland, Naomi

    2008-01-01

    A structured literature review was performed to detail the frequency and etiology of chronic liver disease (CLD) in Aboriginal North Americans. CLD affects Aboriginal North Americans disproportionately and is now one of the most common causes of death. Alcoholic liver disease is the leading etiology of CLD, but viral hepatitis, particularly hepatitis C, is an important and growing cause of CLD. High rates of autoimmune hepatitis and primary biliary cirrhosis (PBC) are reported in regions of coastal British Columbia and southeastern Alaska. Non-alcoholic liver disease is a common, but understudied, cause of CLD. Future research should monitor the incidence and etiology of CLD and should be geographically inclusive. In addition, more research is needed on the treatment of hepatitis C virus (HCV) infection and non-alcoholic fatty liver disease (NAFLD) in this population. PMID:18698674

  15. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population.

    PubMed

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  16. Celiac Disease Autoimmunity in Patients with Autoimmune Diabetes and Thyroid Disease among Chinese Population

    PubMed Central

    Zhao, Zhiyuan; Zou, Jing; Zhao, Lingling; Cheng, Yan; Cai, Hanqing; Li, Mo; Liu, Edwin; Yu, Liping; Liu, Yu

    2016-01-01

    The prevalence of celiac disease autoimmunity or tissue transglutaminase autoantibodies (TGA) amongst patients with type 1 diabetes (T1D) and autoimmune thyroid disease (AITD) in the Chinese population remains unknown. This study examined the rate of celiac disease autoimmunity amongst patients with T1D and AITD in the Chinese population. The study included 178 patients with type 1 diabetes and 119 with AITD where 36 had both T1D and AITD, classified as autoimmune polyglandular syndrome type 3 variant (APS3v). The study also included 145 patients with type 2 diabetes (T2D), 97 patients with non-autoimmune thyroid disease (NAITD), and 102 healthy controls. Serum islet autoantibodies, thyroid autoantibodies and TGA were measured by radioimmunoassay. TGA positivity was found in 22% of patients with either type 1 diabetes or AITD, much higher than that in patients with T2D (3.4%; p< 0.0001) or NAITD (3.1%; P < 0.0001) or healthy controls (1%; p<0.0001). The patients with APS3v having both T1D and AITD were 36% positive for TGA, significantly higher than patients with T1D alone (p = 0.040) or with AITD alone (p = 0.017). T1D and AITD were found to have a 20% and 30% frequency of overlap respectively at diagnosis. In conclusion, TGA positivity was high in the Chinese population having existing T1D and/or AITD, and even higher when both diseases were present. Routine TGA screening in patients with T1D or AITD will be important to early identify celiac disease autoimmunity for better clinical care of patients. PMID:27427767

  17. The complement system in systemic autoimmune disease.

    PubMed

    Chen, Min; Daha, Mohamed R; Kallenberg, Cees G M

    2010-05-01

    Complement is part of the innate immune system. Its major function is recognition and elimination of pathogens via direct killing and/or stimulation of phagocytosis. Activation of the complement system is, however, also involved in the pathogenesis of the systemic autoimmune diseases. Activation via the classical pathway has long been recognized in immune complex-mediated diseases such as cryoglobulinemic vasculitis and systemic lupus erythematosus (SLE). In SLE, the role of complement is somewhat paradoxical. It is involved in autoantibody-initiated tissue damage on the one hand, but, on the other hand, it appears to have protective features as hereditary deficiencies of classical pathway components are associated with an increased risk for SLE. There is increasing evidence that the alternative pathway of complement, even more than the classical pathway, is involved in many systemic autoimmune diseases. This is true for IgA-dominant Henoch Schönlein Purpura, in which additional activation of the lectin pathway contributes to more severe disease. In anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis the complement system was considered not to be involved since immunoglobulin deposition is generally absent in the lesions. However, recent studies, both in human and animal models, demonstrated complement activation via the alternative pathway as a major pathogenic mechanism. Insight into the role of the various pathways of complement in the systemic autoimmune diseases including the vasculitides opens up new ways of treatment by blocking effector pathways of complement. This has been demonstrated for monoclonal antibodies to C5 or C5a in experimental anti-phospholipid antibody syndrome and ANCA-associated vasculitis.

  18. Sex bias in CNS autoimmune disease mediated by androgen control of autoimmune regulator.

    PubMed

    Zhu, Meng-Lei; Bakhru, Pearl; Conley, Bridget; Nelson, Jennifer S; Free, Meghan; Martin, Aaron; Starmer, Joshua; Wilson, Elizabeth M; Su, Maureen A

    2016-01-01

    Male gender is protective against multiple sclerosis and other T-cell-mediated autoimmune diseases. This protection may be due, in part, to higher androgen levels in males. Androgen binds to the androgen receptor (AR) to regulate gene expression, but how androgen protects against autoimmunity is not well understood. Autoimmune regulator (Aire) prevents autoimmunity by promoting self-antigen expression in medullary thymic epithelial cells, such that developing T cells that recognize these self-antigens within the thymus undergo clonal deletion. Here we show that androgen upregulates Aire-mediated thymic tolerance to protect against autoimmunity. Androgen recruits AR to Aire promoter regions, with consequent enhancement of Aire transcription. In mice and humans, thymic Aire expression is higher in males compared with females. Androgen administration and male gender protect against autoimmunity in a multiple sclerosis mouse model in an Aire-dependent manner. Thus, androgen control of an intrathymic Aire-mediated tolerance mechanism contributes to gender differences in autoimmunity. PMID:27072778

  19. Large leg ulcers due to autoimmune diseases

    PubMed Central

    Rozin, Alexander P.; Egozi, Dana; Ramon, Yehuda; Toledano, Kohava; Braun-Moscovici, Yolanda; Markovits, Doron; Schapira, Daniel; Bergman, Reuven; Melamed, Yehuda; Ullman, Yehuda; Balbir-Gurman, Alexandra

    2011-01-01

    Summary Background Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. Case Report Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU’s with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU’s due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU’s healed. Conclusions LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases. PMID:21169912

  20.  An autoimmune polyglandular syndrome complicated with celiac disease and autoimmune hepatitis.

    PubMed

    Dieli-Crimi, Romina; Núñez, Concepción; Estrada, Lourdes; López-Palacios, Natalia

    2016-01-01

     Autoimmune polyglandular syndrome (APS) is a combination of different autoimmune diseases. The close relationship between immune-mediated disorders makes it mandatory to perform serological screening periodically in order to avoid delayed diagnosis of additional autoimmune diseases. We studied a patient with type 1 diabetes (T1D) who later developed an autoimmune thyroid disease (ATD) and was referred to our hospital with a serious condition of his clinical status. The patient was suffering from an advance stage of celiac disease (CD), the delay in its diagnosis and in the establishment of a gluten-free dietled the patient to a severe proteincalorie malnutrition. Later, the patient developed an autoimmune hepatitis (AIH). We consider that clinical deterioration in patients with APS should alert physicians about the possible presence of other immune-mediated diseases. Periodic screening for autoantibodies would help to prevent delayed diagnosis and would improve patient's quality of life. PMID:27236159

  1. A case of autoimmune hepatitis combined with Graves' disease.

    PubMed

    Jhee, Jong Hyun; Kim, Hyun Ju; Kang, Wonseok; Kim, Sewha; Kim, Do Young

    2015-01-01

    A 25-year-old woman presented with jaundice, palpitation, and weight loss of 5 kg during a period of 2 weeks. Laboratory tests showed elevated levels of liver enzymes (AST 1,282 IU/L, ALT 1,119 IU/L) and total bilirubin (6.4 mg/dL); negative for hepatitis virus infection; elevated serum levels of triiodothyronine (T3, 3.60 ng/dL), free thyroxine (fT4, 3.82 ng/dL), and lowered serum level of thyroid stimulating hormone (TSH, <0.025 μIU/mL); and positive for thyroid stimulating antibody and anti-mitochondrial antibody (AMA). The liver biopsy findings were consistent with autoimmune hepatitis (AIH). Accordingly, oral steroid therapy was started with 60 mg of prednisolone under the impression of AIH associated with Graves' disease. After a week of steroid therapy, the clinical manifestation showed significant improvement, with normalization of both liver and thyroid functions. Diagnosis of the liver condition of patients who present with hyperthyroidism and liver dysfunction is important, so that appropriate therapy can be promptly initiated. PMID:25603854

  2. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice. PMID:24951302

  3. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice.

  4. Treating prolactinoma can prevent autoimmune diseases.

    PubMed

    Watad, Abdulla; Versini, Mathilde; Jeandel, Pierre-Yves; Amital, Howard; Shoenfeld, Yehuda

    2015-04-01

    Prolactin (PRL) is a pleiotropic hormone; in addition to a wide variety of endocrine effects, PRL also exhibits immunostimulating effects. Therefore, there is increasing evidence linking PRL with a large number of systemic and organ specific autoimmune diseases. Herein, we report the case of an adolescent girl diagnosed with multiple sclerosis (MS) occurring in the context of untreated prolactinoma evolving since childhood. This raises the exciting question of the involvement of PRL in the pathogenesis of MS. It is likely that early treatment of hyperprolactinemia in this case would have significantly reduced the risk of developing MS or even prevented its occurrence.

  5. Autoimmune vitiligo in rheumatic disease in the mestizo Mexican population

    PubMed Central

    Avalos-Díaz, Esperanza; Pérez-Pérez, Elena; Rodríguez-Rodríguez, Mayra; Pacheco-Tovar, María-Guadalupe; Herrera-Esparza, Rafael

    2016-01-01

    Vitiligo is a chronic disease characterized by the dysfunction or destruction of melanocytes with secondary depigmentation. The aim of the present study was to determine the prevalence of vitiligo associated with autoimmune rheumatic diseases. The clinical records from a 10-year database of patients with rheumatic diseases and associated vitiligo was analysed, with one group of patients having autoimmune rheumatic disease and another non-autoimmune rheumatic disease. Available serum samples were used to assess the anti-melanocyte antibodies. A total of 5,251 individual clinical files were archived in the last 10 years, and these patients underwent multiple rheumatology consultations, with 0.3% of the group presenting with vitiligo. The prevalence of vitiligo in the autoimmune rheumatic disease group was 0.672%, which was mainly associated with lupus and arthritis. However, patients with more than one autoimmune disease had an increased relative risk to develop vitiligo, and anti-melanocyte antibodies were positive in 92% of these patients. By contrast, the prevalence was 0.082% in the group that lacked autoimmune rheumatic disease and had negative autoantibodies. In conclusion, the association between vitiligo and autoimmune rheumatic diseases was relatively low. However, the relative risk increased when there were other autoimmune comorbidities, such as thyroiditis or celiac disease. Therefore, the presence of multiple autoimmune syndromes should be suspected. PMID:27446537

  6. Autoimmune diseases in the TH17 era.

    PubMed

    Mesquita Jr, D; Cruvinel, W M; Câmara, N O S; Kállas, E G; Andrade, L E C

    2009-06-01

    A new subtype of CD4+ T lymphocytes characterized by the production of interleukin 17, i.e., TH17 cells, has been recently described. This novel T cell subset is distinct from type 1 and type 2 T helper cells. The major feature of this subpopulation is to generate significant amounts of pro-inflammatory cytokines, therefore appearing to be critically involved in protection against infection caused by extracellular microorganisms, and in the pathogenesis of autoimmune diseases and allergy. The dynamic balance among subsets of T cells is important for the modulation of several steps of the immune response. Disturbances in this balance may cause a shift from normal immunologic physiology to the development of immune-mediated disorders. In autoimmune diseases, the fine balance between the proportion and degree of activation of the various T lymphocyte subsets can contribute to persistent undesirable inflammatory responses and tissue replacement by fibrosis. This review highlights the importance of TH17 cells in this process by providing an update on the biology of these cells and focusing on their biology and differentiation processes in the context of immune-mediated chronic inflammatory diseases. PMID:19448894

  7. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

    Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

    2006-01-01

    The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

  8. [Probiotics in liver diseases].

    PubMed

    Soriano, Germán; Sánchez, Elisabet; Guarner, Carlos

    2013-01-01

    Alterations in intestinal microbiota and inflammatory response play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and non-alcoholic steatohepatitis. Probiotics can be useful to delay disease progression and to prevent development of complications due to their ability to modulate intestinal flora, intestinal permeability and inflammatory response. Several studies have shown the efficacy of probiotics in the treatment of minimal hepatic encephalopathy and the prevention of episodes of overt hepatic encephalopathy. Probiotics have also been observed to prevent postoperative bacterial infections and to improve liver damage in non-alcoholic steatohepatitis. However, more studies are needed in order to confirm the efficacy and safety of probiotics in patients with liver diseases, and to better understanding of the mechanisms implicated in their effects.

  9. The MicroRNA-21 in Autoimmune Diseases

    PubMed Central

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-01-01

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease. PMID:27271606

  10. The MicroRNA-21 in Autoimmune Diseases.

    PubMed

    Wang, Shaowen; Wan, Xiaochun; Ruan, Qingguo

    2016-06-03

    MicroRNA-21 (miR-21) is an oncomiR and significantly upregulated in a wide range of cancers. It is strongly involved in apoptosis and oncogenesis, since most of its reported targets are tumor suppressors. Recently, miR-21 was found to be correlated with the pathogenesis of autoimmune diseases and may play an essential role in regulating autoimmune responses. In particular, miR-21 promotes Th17 cell differentiation, which mediates the development of multiple autoimmune diseases. In this article, we review the current research on the mechanisms that regulate miR-21 expression, the potential of miR-21 as a diagnostic biomarker for autoimmune disease and the mechanisms by which miR-21 promotes the development of autoimmune disease. We also discussed the therapeutic potential of targeting miR-21 in treating patients with autoimmune disease.

  11. A Genomic Approach to Human Autoimmune Diseases

    PubMed Central

    Pascual, Virginia; Chaussabel, Damien; Banchereau, Jacques

    2010-01-01

    The past decade has seen an explosion in the use of DNA-based microarrays. These techniques permit to assess RNA abundance on a genome-wide scale. Medical applications emerged in the field of cancer, with studies of both solid tumors and hematological malignancies leading to the development of tests that are now used to personalize therapeutic options. Microarrays have also been used to analyze the blood transcriptome in a wide range of diseases. In human autoimmune diseases, these studies are showing potential for identifying therapeutic targets as well as biomarkers for diagnosis, assessment of disease activity and response to treatment. More quantitative and sensitive high throughput RNA profiling methods are starting to be available and will be necessary for transcriptome analyses to become routine tests in the clinical setting. We expect this to crystallize within the coming decade, as they become part of the personalized medicine armamentarium. PMID:20192809

  12. Liver disease and malnutrition.

    PubMed

    Purnak, Tugrul; Yilmaz, Yusuf

    2013-08-01

    Patients with hepatic disorders are exceptionally vulnerable to developing malnutrition because of the key role played by the liver in regulating the nutritional state and the energy balance. Moreover, the presence of chronic liver disorders could reduce the appetite and thus influence the nutrient intake. Poor nutritional status has been shown in various patient groups with hepatic disorders, and particularly in patients with alcoholic cirrhosis who are at high nutritional risk. It is well established that malnourished patients with liver diseases generally have a higher risk of developing adverse clinical outcomes and increased healthcare costs. Nutrition screening with the Subjective Global Assessment and anthropometric measurements are an important first step in the early identification of malnutrition and initiates the whole nutrition care process. It is therefore important for appropriate nutrition policies and protocols to be implemented so that all patients with chronic liver diseases are monitored closely from a nutritional standpoint. Early and evidence-based nutritional interventions are eagerly needed to minimize the nutritional decline associated with chronic liver disorders and ultimately improve the prognosis of such patients. This review includes a comprehensive analysis of methods to identify malnutrition in patients with chronic liver diseases as well as the extent and impact of the malnutrition problem in selected patient populations.

  13. Psoriasis is not an autoimmune disease?

    PubMed

    Fry, Lionel; Baker, Barbara S; Powles, Anne V; Engstrand, Lars

    2015-04-01

    The concept that psoriasis is an autoimmune disease needs to be questioned. The autoimmune label has been based on molecular mimicry between streptococcal and keratin proteins and the existence of homologous peptides between these proteins. However, it is only peripheral blood CD8, and not CD4, T lymphocytes that respond to the homologous peptides. This ignores the fact that it is CD4 T cells which are necessary to initiate psoriasis. Recent studies on skin bacterial microbiota have found a variety of bacteria in both normal skin and psoriatic lesions. In biopsy specimens, the most common phylum was Firmicutes and the most common genus streptococcus in both psoriasis and normal skin. The innate immune system is activated in psoriasis, and recent genetic findings have shown the majority of susceptibility loci are associated with innate immunity. There is a known clinical relationship between both Crohn's disease (CD) and periodontitis, and psoriasis, and patients with psoriasis share mutations in some innate immunity genes with individuals with CD. It is now accepted that CD is due to a breakdown of immune tolerance (dysbiosis) to bacteria in the intestine. These findings suggest that psoriasis is initiated by an abnormal response to bacteria in the skin due to genetic factors.

  14. Spondyloarthropathies in Autoimmune Diseases and Vice Versa

    PubMed Central

    Pérez-Fernández, Oscar M.; Mantilla, Rubén D.; Cruz-Tapias, Paola; Rodriguez-Rodriguez, Alberto; Rojas-Villarraga, Adriana; Anaya, Juan-Manuel

    2012-01-01

    Polyautoimmunity is one of the major clinical characteristics of autoimmune diseases (ADs). The aim of this study was to investigate the prevalence of ADs in spondyloarthropathies (SpAs) and vice versa. This was a two-phase cross-sectional study. First, we examined the presence of ADs in a cohort of patients with SpAs (N = 148). Second, we searched for the presence of SpAs in a well-defined group of patients with ADs (N = 1077) including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS). Among patients with SpAs, ankylosing spondylitis was observed in the majority of them (55.6%). There were two patients presenting with SS in the SpA group (1.4%) and 5 patients with autoimmune thyroiditis (3.5%). The global prevalence of ADs in SpAs was 4.86%. In the ADs group, there were 5 patients with SpAs (0.46%). Our results suggest a lack of association between SpAs and ADs. Accordingly, SpAs might correspond more to autoinflammatory diseases rather than to ADs. PMID:22400103

  15. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  16. Alcoholic liver disease: Treatment

    PubMed Central

    Suk, Ki Tae; Kim, Moon Young; Baik, Soon Koo

    2014-01-01

    The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation. PMID:25278689

  17. Ovarian autoimmune disease: clinical concepts and animal models

    PubMed Central

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K; Jasti, Susmita; Stevens, Anne M; Petroff, Brian K; Petroff, Margaret G

    2014-01-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models. PMID:25327908

  18. Infections as a cause of autoimmune rheumatic diseases.

    PubMed

    Sakkas, Lazaros I; Bogdanos, Dimitrios P

    2016-12-01

    Exogenous and endogenous environmental exposures and particularly infections may participate in the breakage of tolerance and the induction of autoimmunity in rheumatic diseases. Response to infections apparently occurs years before clinical manifestations and features of autoimmunity, such as autoantibodies, are detected years before clinical manifestations in autoimmune rheumatic diseases. In this review, we summarize the current evidence for a potential causal link between infectious agents and rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjogren's syndrome and ANCA-associated vasculitis. PMID:27629582

  19. An Overview of Organ-Specific Autoimmune Diseases Including Immunotherapy.

    PubMed

    Mastrandrea, Lucy D

    2015-01-01

    A significant number of individuals are affected by autoimmune diseases, which are caused by aberrant recognition of self by the immune system. A wide variety of cells and organ systems are targets of pathologic activation of the immune mediators. Effective and safe therapies aimed at managing the chronic inflammatory aspect of many autoimmune diseases remain elusive. This review will focus on the available interventions and discuss the future of the field to prevent organ destruction by the autoimmune process. PMID:26575465

  20. Pharmacometabolomics-aided Pharmacogenomics in Autoimmune Disease.

    PubMed

    Katsila, Theodora; Konstantinou, Evangelia; Lavda, Ioanna; Malakis, Harilaos; Papantoni, Ioanna; Skondra, Lamprini; Patrinos, George P

    2016-03-01

    Inter-individual variability has been a major hurdle to optimize disease management. Precision medicine holds promise for improving health and healthcare via tailor-made therapeutic strategies. Herein, we outline the paradigm of "pharmacometabolomics-aided pharmacogenomics" in autoimmune diseases. We envisage merging pharmacometabolomic and pharmacogenomic data (to address the interplay of genomic and environmental influences) with information technologies to facilitate data analysis as well as sense- and decision-making on the basis of synergy between artificial and human intelligence. Humans can detect patterns, which computer algorithms may fail to do so, whereas data-intensive and cognitively complex settings and processes limit human ability. We propose that better-informed, rapid and cost-effective omics studies need the implementation of holistic and multidisciplinary approaches.

  1. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  2. Toll-like receptors and liver disease.

    PubMed

    Kesar, Vivek; Odin, Joseph A

    2014-02-01

    Toll-like receptors (TLRs) are pattern recognition receptors that play an important role in host defence by recognizing pathogen-associated molecular patterns (PAMP). Recent studies indicate that TLR signalling plays an important role in progression of chronic liver diseases. Ongoing clinical trials suggest that therapeutic manipulation of TLR pathways may offer novel means of reversing chronic liver diseases. Upon activation by their respective ligands, TLRs initiate an intracellular pro-inflammatory/anti-inflammatory signalling cascade via recruitment of various adaptor proteins. TLR associated signalling pathways are tightly regulated to keep a check on inappropriate production of pro-inflammatory cytokines and interferons thereby preventing various autoimmune and inflammatory processes. Herein, we review the current state of knowledge of hepatic distribution, signalling pathways and therapeutic modulation of TLRs in chronic liver diseases. PMID:24118797

  3. Introducing Polyautoimmunity: Secondary Autoimmune Diseases No Longer Exist

    PubMed Central

    Rojas-Villarraga, Adriana; Amaya-Amaya, Jenny; Rodriguez-Rodriguez, Alberto; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Similar pathophysiological mechanisms within autoimmune diseases have stimulated searches for common genetic roots. Polyautoimmunity is defined as the presence of more than one autoimmune disease in a single patient. When three or more autoimmune diseases coexist, this condition is called multiple autoimmune syndrome (MAS). We analyzed the presence of polyautoimmunity in 1,083 patients belonging to four autoimmune disease cohorts. Polyautoimmunity was observed in 373 patients (34.4%). Autoimmune thyroid disease (AITD) and Sjögren's syndrome (SS) were the most frequent diseases encountered. Factors significantly associated with polyautoimmunity were female gender and familial autoimmunity. Through a systematic literature review, an updated search was done for all MAS cases (January 2006–September 2011). There were 142 articles retrieved corresponding to 226 cases. Next, we performed a clustering analysis in which AITD followed by systemic lupus erythematosus and SS were the most hierarchical diseases encountered. Our results indicate that coexistence of autoimmune diseases is not uncommon and follows a grouping pattern. Polyautoimmunity is the term proposed for this association of disorders, which encompasses the concept of a common origin for these diseases. PMID:22454759

  4. Arsenic and liver disease.

    PubMed

    Guha Mazumder, D N

    2001-06-01

    The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

  5. Non-MHC genes linked to autoimmune disease.

    PubMed

    Deitiker, Philip; Atassi, M Zouhair

    2012-01-01

    The genetic traits that result in autoimmune diseases represent complicating factors in explicating the molecular and cellular elements of autoimmune responses and how these responses can be overcome or manipulated. This article focuses on the major non-major histocompatibility complex genes that have been found to be linked to autoimmune diseases. A given gene may associate with a number of autoimmune diseases and, conversely, a given disease may link to a number of common autoimmune disease (AD) genes. Collaboration and interaction among genes and the number of diseases that develop and the extensive risk factors shared among ADs further complicate the outcome. This article describes the various relationships between gene regions associated with multiple ADs and the complexity of those relationships.

  6. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes?

    PubMed Central

    Cordiano, I; Betterle, C; Spadaccino, C A; Soini, B; Girolami, A; Fabris, F

    1998-01-01

    The pathogenesis of thrombocytopenia associated with TAD and the occurrence of overlapping traits between TAD and AITP are still a matter of debate. For this reason, we investigated for the presence and specificity of platelet and thyroid autoantibodies in 18 TAD patients with thrombocytopenia, 19 TAD patients without thrombocytopenia and in 22 patients with primary AITP without clinical signs of TAD. Platelet-associated IgG and/or specific circulating platelet autoantibodies were detected in 83% of patients with TAD and thrombocytopenia, in 10% of patients with TAD without thrombocytopenia and in 86% of patients with primary AITP. The reactivity of serum autoantibodies, assayed by MoAb immobilization of platelet antigens (MAIPA), was directed against platelet glycoproteins Ib and/or IIb/IIIa in 50% of the patients with TAD and thrombocytopenia, as in 46% of the patients with primary AITP. Thyroid autoantibodies were found in 89% of patients with TAD and thrombocytopenia, in 95% of patients with TAD without thrombocytopenia, and in 18% of patients with primary AITP. Thyrotropin (TSH) levels determined in three of four AITP patients with thyroid autoantibodies revealed a subclinical hyperthyroidism in one patient. The present study supports the autoimmune aetiology of thrombocytopenia associated with TAD, since the prevalence and specificity of platelet autoantibodies are similar in TAD and primary AITP. The results indicate also that there exists an overlap between thyroid and platelet autoimmunity with or without clinical manifestations. PMID:9737665

  7. Celiac Disease and Autoimmune-Associated Conditions

    PubMed Central

    Lauret, Eugenia; Rodrigo, Luis

    2013-01-01

    Celiac disease (CD) is frequently accompanied by a variety of extradigestive manifestations, thus making it a systemic disease rather than a disease limited to the gastrointestinal tract. This is primarily explained by the fact that CD belongs to the group of autoimmune diseases. The only one with a known etiology is related to a permanent intolerance to gluten. Remarkable breakthroughs have been achieved in the last decades, due to a greater interest in the diagnosis of atypical and asymptomatic patients, which are more frequent in adults. The known presence of several associated diseases provides guidance in the search of oligosymptomatic cases as well as studies performed in relatives of patients with CD. The causes for the onset and manifestation of associated diseases are diverse; some share a similar genetic base, like type 1 diabetes mellitus (T1D); others share pathogenic mechanisms, and yet, others are of unknown nature. General practitioners and other specialists must remember that CD may debut with extraintestinal manifestations, and associated illnesses may appear both at the time of diagnosis and throughout the evolution of the disease. The implementation of a gluten-free diet (GFD) improves the overall clinical course and influences the evolution of the associated diseases. In some cases, such as iron deficiency anemia, the GFD contributes to its disappearance. In other disorders, like T1D, this allows a better control of the disease. In several other complications and/or associated diseases, an adequate adherence to a GFD may slow down their evolution, especially if implemented during an early stage. PMID:23984314

  8. HLA and autoimmune endocrine disease 1985.

    PubMed

    Farid, N R; Thompson, C

    1986-02-01

    We typed patient groups with type I diabetes (n = 78), Graves' disease (n = 81), goitrous autoimmune (n = 52), "silent" (n = 18) and postpartum thyroiditis (n = 15) for human leucocyte antigens (HLA) A, B, C, DR and DQ. The results were compared to those obtained from 256 healthy controls typed for HLA-A, -B, -C and 140 typed for -DR. All these 140 controls were genotyped. Previously described associations of DR3 (OR (odds ratio) = 2.68, p less than 0.005) and DR4 (OR = 3.26, p less than 0.0001) in type I diabetes is confirmed. In this series, however, HLA-DR3/DR4 heterozygotes were apparently at no greater risk for type I diabetes than DR3 or DR4 homozygotes. The relative risk conferred by DR3/DR4 heterozygotes (6.48) was less than that for DR3 homozygosity (2.8), suggesting a recessive major histocompatibility complex-related susceptibility to type I diabetes. Graves' disease was associated with DR3 (OR = 3.02, p less than 0.0005); the increased frequency of DR3 homozygotes in this series is consistent with recessive HLA-linked susceptibility to Graves' disease proposed on the basis of family data. Hashimoto's thyroiditis, on the other hand, was associated with HLA-DR4 (OR = 3.08, p less than 0.0001), the latter finding confirming our earlier report on 21 patients. The increase of HLA-DR4 in both post-partum and silent thyroiditis suggests that these conditions are immunogenetically related, and may well represent variants of chronic autoimmune thyroiditis.

  9. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  10. Modeling toxicodynamic effects of trichloroethylene on liver in mouse model of autoimmune hepatitis

    SciTech Connect

    Gilbert, Kathleen M.; Reisfeld, Brad; Zurlinden, Todd J.; Kreps, Meagan N.; Erickson, Stephen W.; Blossom, Sarah J.

    2014-09-15

    Chronic exposure to industrial solvent and water pollutant trichloroethylene (TCE) in female MRL +/+ mice generates disease similar to human autoimmune hepatitis. The current study was initiated to investigate why TCE-induced autoimmunity targeted the liver. Compared to other tissues the liver has an unusually robust capacity for repair and regeneration. This investigation examined both time-dependent and dose-dependent effects of TCE on hepatoprotective and pro-inflammatory events in liver and macrophages from female MRL +/+ mice. After a 12-week exposure to TCE in drinking water a dose-dependent decrease in macrophage production of IL-6 at both the transcriptional and protein level was observed. A longitudinal study similarly showed that TCE inhibited macrophage IL-6 production. In terms of the liver, TCE had little effect on expression of pro-inflammatory genes (Tnfa, Saa2 or Cscl1) until the end of the 40-week exposure. Instead, TCE suppressed hepatic expression of genes involved in IL-6 signaling (Il6r, gp130, and Egr1). Linear regression analysis confirmed liver histopathology in the TCE-treated mice correlated with decreased expression of Il6r. A toxicodynamic model was developed to estimate the effects of TCE on IL-6 signaling and liver pathology under different levels of exposure and rates of repair. This study underlined the importance of longitudinal studies in mechanistic evaluations of immuntoxicants. It showed that later-occurring liver pathology caused by TCE was associated with early suppression of hepatoprotection rather than an increase in conventional pro-inflammatory events. This information was used to create a novel toxicodynamic model of IL-6-mediated TCE-induced liver inflammation. - Highlights: • We developed a toxicodynamic model to study effects of trichloroethylene on liver. • We examined protective as well as pro-inflammatory events in the liver. • Trichloroethylene inhibits IL-6 production by macrophages. • Trichloroethylene

  11. Subsequent leukaemia in autoimmune disease patients.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Ji, Jianguang; Sundquist, Jan; Sundquist, Kristina

    2013-06-01

    Previous studies have shown that patients diagnosed with some autoimmune (AI) diseases are at an increased risk of leukaemia but limited data are available on survival. We systematically analysed the risks (standardized incidence ratio, SIR) and survival (hazard ratio, HR) in nine types of leukaemia among 402 462 patients hospitalized for any of 33 AI diseases and compared to persons not hospitalized for AI diseases. Risk for all leukaemia was increased after 13 AI diseases and survival was decreased after six AI diseases. SIRs were increased after all AI diseases for seven types of leukaemia, including SIR 1·69 (95% confidence interval (CI): 1·29-2·19) for acute lymphoblastic leukaemia (ALL), 1·85 (95% CI: 1·65-2·07) for acute myeloid leukaemia, 1·68 (95% CI: 1·37-2·04) for chronic myeloid leukaemia, 2·20 (95% CI: 1·69-2·81) for 'other myeloid leukaemia', 2·45 (95% 1·99-2·98) for 'other and unspecified leukaemia', 1·81 (95% CI: 1·11-2·81) for monocytic leukaemia, and 1·36 (95% CI: 1·08-1·69) for myelofibrosis. The HRs were increased for four types of leukaemia, most for myelofibrosis (1·74, 95% CI: 1·33-2·29) and ALL (1·42, 95% CI: 1·03-1·95). Some AI diseases, including rheumatoid arthritis, were associated with increased SIRs and HRs in many types of leukaemia. The present data showed increases in risk and decreases in survival for many types of leukaemia after various AI diseases. Leukaemia is a rare complication in AI disease but findings about this comorbidity at the time of leukaemia diagnosis may help to optimize the treatment and improve survival.

  12. Liver fibrosis markers in alcoholic liver disease.

    PubMed

    Chrostek, Lech; Panasiuk, Anatol

    2014-07-01

    Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients. PMID:25009372

  13. Emerging role of long noncoding RNAs in autoimmune diseases.

    PubMed

    Wu, Guo-Cui; Pan, Hai-Feng; Leng, Rui-Xue; Wang, De-Guang; Li, Xiang-Pei; Li, Xiao-Mei; Ye, Dong-Qing

    2015-09-01

    Long noncoding RNA (lncRNA), with size larger than 200 nucleotides, is a new class of noncoding RNA. Emerging evidence has revealed that lncRNAs play a key role in the regulation of immunological functions and autoimmunity. Herein, we review the recent findings of lncRNA regulation in immune functions and in the development of autoimmunity and autoimmune disease. In addition, we focus on the involvement of lncRNA regulation in innate and adaptive immune responses, immune cell development, and differential expression of lncRNAs in autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes mellitus (T1DM), multiple sclerosis (MS), autoimmune thyroid disease (AITD), psoriasis, polymyositis/dermatomyositis (PM/DM) and Crohn's disease (CD). PMID:25989481

  14. 'De novo' and 'recurrent' autoimmune hepatitis after liver transplantation: A comprehensive review.

    PubMed

    Kerkar, Nanda; Yanni, George

    2016-01-01

    Autoimmune Hepatitis (AIH) is a chronic progressive inflammatory disease of the liver that responds to immunosuppressive therapy. In patients with AIH who have an acute liver failure presentation or those who develop end stage liver disease despite medical therapy, liver transplantation (LT) may become necessary. Despite good outcomes after LT, AIH can develop/recur in the allograft with an estimated incidence of recurrence between 8 and 12% at 1 year and 36-68% at 5 years. The presence of non-organ specific autoantibodies, elevated serum aminotransferases and immunoglobulin G as well as the characteristic histologic features of interface hepatitis (peri-portal plasma cell infiltration) characterize recurrence of disease. De novo AIH is the development of features of classical AIH in the allograft of patients who have not been transplanted for AIH. There are several reports in the pediatric transplant population, where administering immunosuppressive therapy in the regimen used to treat AIH has stabilized graft function in de novo AIH. In adults, hepatitis C (HCV) is the most common indication for LT and HCV often recurs after LT, requiring treatment with Interferon and Ribavirin. Labeling the graft dysfunction 'de novo AIH' can be problematic in this context, particularly if HCV RNA is positive at that time. Some have chosen to give other names like 'graft dysfunction mimicking AIH' and 'plasma cell hepatitis'. Regardless of the nomenclature, autoimmune liver graft dysfunction, if managed appropriately with the treatment regimen used to treat AIH, can save grafts and patients. The mechanism causing recurrent or de novo AIH after LT remains unknown. Several mechanisms have been implicated in this loss of self-tolerance including impaired thymic regulation, impaired activity of T regulatory cells, molecular mimicry, calcineurin inhibitors, glutathione-s transferase and genetic polymorphisms. While the phenotype of de novo AIH in pediatrics has been uniform, it has

  15. Ocular Involvement in Systemic Autoimmune Diseases.

    PubMed

    Generali, Elena; Cantarini, Luca; Selmi, Carlo

    2015-12-01

    Eye involvement represents a common finding in patients with systemic autoimmune diseases, particularly rheumatoid arthritis, Sjogren syndrome, seronegative spondyloarthropathy, and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. The eye is a privileged immune site but commensal bacteria are found on the ocular surface. The eye injury may be inflammatory, vascular or infectious, as well as iatrogenic, as in the case of hydroxychloroquine, chloroquine, corticosteroids, and bisphosphonates. Manifestations may affect different components of the eye, with episcleritis involving the episclera, a thin layer of tissue covering the sclera; scleritis being an inflammation of the sclera potentially leading to blindness; keratitis, referring to corneal inflammation frequently associated with scleritis; and uveitis as the inflammation of the uvea, including the iris, ciliary body, and choroid, subdivided into anterior, posterior, or panuveitis. As blindness may result from the eye involvement, clinicians should be aware of the possible manifestations and their management also independent of the ophthalmologist opinion as the therapeutic approach generally points to the underlying diseases. In some cases, the eye involvement may have a diagnostic implication, as for episcleritis in rheumatoid arthritis, or acute anterior uveitis in seronegative spondyloarthritis. Nonetheless, some conditions lack specificity, as in the case of dry eye which affects nearly 30 % of the general population. The aim of this review is to elucidate to non-ophthalmologists the major ocular complications of rheumatic diseases and their specific management and treatment options.

  16. Involvement of dendritic cells in autoimmune diseases in children

    PubMed Central

    López de Padilla, Consuelo M; Reed, Ann M

    2007-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells that are specialized in the uptake of antigens and their transport from peripheral tissues to the lymphoid organs. Over the last decades, the properties of DCs have been intensely studied and much knowledge has been gained about the role of DCs in various diseases and health conditions where the immune system is involved, particularly in cancer and autoimmune disorders. Emerging clues in autoimmune diseases, suggest that dendritic cell dysregulation might be involved in the development of various autoimmune disorders in both adults and children. However, studies investigating a possible contribution of DCs in autoimmune diseases in the pediatric population alone are scanty. The purpose of this review is to give a general overview of the current literature on the relevance of dendritic cells in the most common autoimmune conditions of childhood. PMID:17625003

  17. Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease

    PubMed Central

    Rahat, Michal A.

    2016-01-01

    Cancer and autoimmune diseases are fundamentally different pathological conditions. In cancer, the immune response is suppressed and unable to eradicate the transformed self-cells, while in autoimmune diseases it is hyperactivated against a self-antigen, leading to tissue injury. Yet, mechanistically, similarities in the triggering of the immune responses can be observed. In this review, we highlight some parallel aspects of the microenvironment in cancer and autoimmune diseases, especially hypoxia, and the role of macrophages, neutrophils, and their interaction. Macrophages, owing to their plastic mode of activation, can generate a pro- or antitumoral microenvironment. Similarly, in autoimmune diseases, macrophages tip the Th1/Th2 balance via various effector cytokines. The contribution of neutrophils, an additional plastic innate immune cell population, to the microenvironment and disease progression is recently gaining more prominence in both cancer and autoimmune diseases, as they can secrete cytokines, chemokines, and reactive oxygen species (ROS), as well as acquire an enhanced ability to produce neutrophil extracellular traps (NETs) that are now considered important initiators of autoimmune diseases. Understanding the contribution of macrophages and neutrophils to the cancerous or autoimmune microenvironment, as well as the role their interaction and cooperation play, may help identify new targets and improve therapeutic strategies. PMID:26997761

  18. Inflammatory pseudotumor of the liver and peripheral eosinophilia in autoimmune pancreatitis

    PubMed Central

    Sasahira, Naoki; Kawabe, Takao; Nakamura, Akira; Shimura, Kenji; Shimura, Haruhisa; Itobayashi, Ei; Asada, Manabu; Shiratori, Yasushi; Omata, Masao

    2005-01-01

    AIM: Inflammatory pseudotumor (IPT) of the liver is a rare benign lesion, the etiology of which remains obscure. It is not associated with any particular diseases apart from phlebitis and Crohn’s disease. METHODS: A middle-aged male with hepatic IPT and peripheral eosinophilia associated with autoimmune pancreatitis (AIP) was selected for this study and review of literature. RESULTS: A 59-year-old male was admitted with obstructive jaundice, marked eosinophilia (1343/mm3) and hypergammaglobulinemia (4145 mg/dL). Imaging techniques revealed dilatation of the intrahepatic bile duct, stenosis of the common bile duct with diffuse wall thickening, gallbladder wall thickening, irregular narrowing of the pancreatic duct, and swelling of the pancreatic parenchyma. Multiple liver masses were also demonstrated and diagnosed as IPT by biopsy specimens. Six months later, the abnormal features of the biliary tree remarkably improved by the oral administration of prednisolone, and the liver masses disappeared. The swelling of the pancreatic head also improved. The peripheral eosinophil count normalized. IPT associated with AIP, as we know, has not been reported in the literature. The clinical features of the present case mimicked those of pancreatic cancer with liver metastasis. This case deserves to be documented to prevent misdiagnosis of similar cases. PMID:15682495

  19. Autoimmune thyroid disease in systemic lupus erythematosus

    PubMed Central

    Pyne, D; Isenberg, D

    2002-01-01

    Objective: To report the prevalence of autoimmune thyroid disease and thyroid antibodies in 300 patients with SLE, followed up at our centre between 1978 and 2000, by a retrospective analysis of case notes. Results: The prevalence (5.7%) of hypothyroidism in our cohort was higher than in the normal population (1%), while that of hyperthyroidism (1.7%) was not significantly different. Overall 42/300 (14%) of our cohort had thyroid antibodies, rising to 15/22 (68%) in the subgroup who also had thyroid disease (p<0.001). Both antimicrosomal and antithyroglobulin antibodies were detected. The antibodies were found in equally high frequency in the hyperthyroid subgroup (80% patients), whereas in the hypothyroid subgroup antimicrosomal antibodies were more frequent than antithyroglobulin antibodies (64% v 41%). There was no significant difference in the frequency with which antimicrosomal or antithyroglobulin antibodies were detected between the hyperthyroid and hypothyroid subgroups (p>0.2). Conclusion: Our patients with SLE had a prevalence of hypothyroidism, but not hyperthyroidism, greater than that of the normal population. The presence of either condition was associated with a higher frequency of both antimicrosomal and antithyroglobulin antibodies. PMID:11779764

  20. AUTOIMMUNE DISEASE DURING PREGNANCY AND THE MICROCHIMERISM LEGACY OF PREGNANCY

    PubMed Central

    Adams Waldorf, Kristina M.; Nelson, J. Lee

    2009-01-01

    Pregnancy has both short-term effects and long-term consequences. For women who have an autoimmune disease and subsequently become pregnant, pregnancy can induce amelioration of the mother’s disease, such as in rheumatoid arthritis, while exacerbating or having no effect on other autoimmune diseases like systemic lupus erythematosus. That pregnancy also leaves a long-term legacy has recently become apparent by the discovery that bi-directional cell trafficking results in persistence of fetal cells in the mother and of maternal cells in her offspring for decades after birth. The long-term persistence of a small number of cells (or DNA) from a genetically disparate individual is referred to as microchimerism. While microchimerism is common in healthy individuals and is likely to have health benefits, microchimerism has been implicated in some autoimmune diseases such as systemic sclerosis. In this paper, we will first discuss short-term effects of pregnancy on women with autoimmune disease. Pregnancy-associated changes will be reviewed for selected autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease. The pregnancy-induced amelioration of rheumatoid arthritis presents a window of opportunity for insights into both immunological mechanisms of fetal-maternal tolerance and pathogenic mechanisms in autoimmunity. A mechanistic hypothesis for the pregnancy-induced amelioration of rheumatoid arthritis will be described. We will then discuss the legacy of maternal-fetal cell transfer from the perspective of autoimmune diseases. Fetal and maternal microchimerism will be reviewed with a focus on systemic sclerosis (scleroderma), autoimmune thyroid disease, neonatal lupus and type I diabetes mellitus. PMID:18716941

  1. Endocannabinoids in Liver Disease

    PubMed Central

    Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

    2010-01-01

    Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

  2. Antigen-based immunotherapy for autoimmune disease: current status

    PubMed Central

    Hirsch, Darren Lowell; Ponda, Punita

    2015-01-01

    Autoimmune diseases are common chronic disorders that not only have a major impact on the quality of life but are also potentially life-threatening. Treatment modalities that are currently favored have conferred significant clinical benefits, but they may have considerable side effects. An optimal treatment strategy for autoimmune disease would specifically target disease-associated antigens and limit systemic side effects. Similar to allergen-specific immunotherapy for allergic rhinitis, antigen-specific immunotherapy for autoimmune disease aims to induce immune deviation and promote tolerance to specific antigens. In this review, we present the current status of studies and clinical trials in both human and animal hosts that use antigen-based immunotherapy for autoimmune disease. PMID:27471707

  3. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization. PMID:27605851

  4. Alloimmunization in multitransfused liver disease patients: Impact of underlying disease

    PubMed Central

    Bajpai, Meenu; Gupta, Shruti; Jain, Priyanka

    2016-01-01

    Introduction: Transfusion support is vital to the management of patients with liver diseases. Repeated transfusions are associated with many risks such as transfusion-transmitted infection, transfusion immunomodulation, and alloimmunization. Materials and Methods: A retrospective data analysis of antibody screening and identification was done from February 2012 to February 2014 to determine the frequency and specificity of irregular red-cell antibodies in multitransfused liver disease patients. The clinical and transfusion records were reviewed. The data was compiled, statistically analyzed, and reviewed. Results: A total of 842 patients were included in our study. Alloantibodies were detected in 5.22% of the patients. Higher rates of alloimmunization were seen in patients with autoimmune hepatitis, cryptogenic liver disease, liver damage due to drugs/toxins, and liver cancer patients. Patients with alcoholic liver disease had a lower rate of alloimmunization. The alloimmunization was 12.7% (23/181) in females and 3.17% (21/661) in males. Antibodies against the Rh system were the most frequent with 27 of 44 alloantibodies (61.36%). The most common alloantibody identified was anti-E (11/44 cases, 25%), followed by anti-C (6/44 cases, 13.63%). Conclusion: Our findings suggest that alloimmunization rate is affected by underlying disease. Provision of Rh and Kell phenotype-matched blood can significantly reduce alloimmunization.

  5. [Iron and liver disease].

    PubMed

    Miyanishi, Koji; Kato, Junji

    2016-07-01

    Free iron in the liver is believed to facilitate the formation of reactive oxygen species (ROS), including hydroxyl radicals (*OH), which cause oxidative damage of numerous cellular components such as lipids, proteins, and nucleic acids, and also upregulate collagen synthesis. The *OH radical is known to generate promutagenic bases such as 8-hydroxy-2-deoxyguanosine (8-OHdG). In cases with chronic hepatitis C, long-term iron reduction therapy reduced the activity of hepatitis, suppressed fibrosis, and prevented hepatocarcinogenesis. In nonalcoholic steatohepatitis (NASH) livers, hepatic iron accumulation as well as oxidative DNA damage significantly increased. Humoral factor(s) in NASH serum may upregulate DMT1 expression in small intestine. Iron reduction therapy for NASH patients has a potential to reduce disease activity as well as hepatic oxidative damage. PMID:27455806

  6. De novo autoimmune hepatitis in liver transplant: State-of-the-art review.

    PubMed

    Vukotic, Ranka; Vitale, Giovanni; D'Errico-Grigioni, Antonia; Muratori, Luigi; Andreone, Pietro

    2016-03-14

    In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necro-inflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of non-organ specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management.

  7. De novo autoimmune hepatitis in liver transplant: State-of-the-art review

    PubMed Central

    Vukotic, Ranka; Vitale, Giovanni; D’Errico-Grigioni, Antonia; Muratori, Luigi; Andreone, Pietro

    2016-01-01

    In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necro-inflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of non-organ specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management. PMID:26973387

  8. De novo autoimmune hepatitis in liver transplant: State-of-the-art review.

    PubMed

    Vukotic, Ranka; Vitale, Giovanni; D'Errico-Grigioni, Antonia; Muratori, Luigi; Andreone, Pietro

    2016-03-14

    In the two past decades, a number of communications, case-control studies, and retrospective reports have appeared in the literature with concerns about the development of a complex set of clinical, laboratory and histological characteristics of a liver graft dysfunction that is compatible with autoimmune hepatitis. The de novo prefix was added to distinguish this entity from a pre-transplant primary autoimmune hepatitis, but the globally accepted criteria for the diagnosis of autoimmune hepatitis have been adopted in the diagnostic algorithm. Indeed, de novo autoimmune hepatitis is characterized by the typical liver necro-inflammation that is rich in plasma cells, the presence of interface hepatitis and the consequent laboratory findings of elevations in liver enzymes, increases in serum gamma globulin and the appearance of non-organ specific auto-antibodies. Still, the overall features of de novo autoimmune hepatitis appear not to be attributable to a univocal patho-physiological pathway because they can develop in the patients who have undergone liver transplantation due to different etiologies. Specifically, in subjects with hepatitis C virus recurrence, an interferon-containing antiviral treatment has been indicated as a potential inception of immune system derangement. Herein, we attempt to review the currently available knowledge about de novo liver autoimmunity and its clinical management. PMID:26973387

  9. Anti-soluble liver antigen/liver-pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis.

    PubMed

    Vitozzi, Susana; Djilali-Saiah, Idriss; Lapierre, Pascal; Alvarez, Fernando

    2002-12-01

    Antibodies against soluble liver antigen/liver-pancreas (SLA/LP) have been associated with severe autoimmune hepatitis (AIH) and poor outcome, but most of these reports have focused on adult patients. The aim of this study was to assess the prevalence and clinical significance of anti-SLA/LP antibodies in a pediatric population with AIH. We developed a quantitative enzyme-linked immunoassay (ELISA), a Western blot (WB) and an immunoprecipitation assay (IPA) based on recombinant cDNA from activated Jurkat cells. The specificity of these tests was validated by testing 200 serum samples from healthy subjects, and from patients with liver and non-liver diseases. Anti-SLA/LP antibodies were found in patients with type 1 and type 2 AIH. The prevalence of these antibodies in patients with type 1 AIH was: 42% when tested by ELISA, 15% by WB and 50% by IPA. In patients with type 2 AIH, the prevalence rates were 42% by ELISA, 18% by WB and 44% by IPA. The mean titer values for anti-SLA/LP antibodies was significantly higher in type 2 AIH (1:1,300 +/- 339) than in type 1 AIH (1:600 +/- 71; p < 0.0001) and closely associated with higher titers of anti-liver kidney microsome type 1 (LKM1) and anti-liver cytosol type 1 (LC1) antibodies in sera. The presence of anti-SLA/LP showed a significant female preponderance in type 1 and 2 AIH patients (p = 0.0003 and p = 0.003, respectively), and was significantly correlated with a lower age at diagnosis (p = 0.05) in type 1 AIH patients. In conclusion, anti-SLA/LP antibodies in pediatric patients are associated with both type 1 and 2 AIH.

  10. Interventional Treatments for Liver Disease

    MedlinePlus

    ... Search Patient information Membership Directory (SIR login) Interventional Radiology Interventional Treatments for Liver Disease There are a ... liver that can be treated with nonsurgical, interventional radiology techniques. Portal Hypertension Seen most frequently in patients ...

  11. Autoimmune disease: Conceptual history and contributions of ocular immunology.

    PubMed

    Margo, Curtis E; Harman, Lynn E

    2016-01-01

    Medical historians identify the mid-20th century as the time when the scientific and medical communities acknowledged the existence of autoimmune disease. Several conditions including sympathetic ophthalmia and endophthalmitis phacoanaphylactica, however, were proposed as autoimmune disorders much earlier. During the first half of the century, autoimmune disease was viewed as biologically implausible. Paul Ehrlich coined the term horror autotoxicus to emphasize that autoimmunity would contradict nature's aversion to self-injury. The discoveries of allergy and anaphylaxis were the first clues that the immune system was capable of self-harm. A major obstacle to comprehending the pathogenesis of autoimmunity was how the immune system distinguishes foreign from self, a process eventually understood in the context of immune tolerance. Investigators of sympathetic ophthalmia and endophthalmitis phacoanaphylactica were positioned to invalidate horror autotoxicus but lacked sufficiently convincing experimental and clinical evidence to accomplish the task. Seminal studies of chronic thyroiditis and a series of clinical laboratory breakthroughs led to the general acceptance of autoimmune disease in the 1950s. The travails encountered by ophthalmic investigators offer insights into the how medical ideas take shape. We review the contributions of ocular immunology to the conceptual development of autoimmune disease and explore the reasons why the concept caught on slowly. PMID:27131478

  12. DNA methylation perspectives in the pathogenesis of autoimmune diseases.

    PubMed

    Sun, Bao; Hu, Lei; Luo, Zhi-Ying; Chen, Xiao-Ping; Zhou, Hong-Hao; Zhang, Wei

    2016-03-01

    DNA methylation is now widely recognized as being critical to maintain the function of immune cells. Recent studies suggest that aberrant DNA methylation levels not only can result in immune cells autoreactivity in vitro, but also are related to autoimmunity in vivo. Environmental factors and genetic polymorphisms cause abnormal methylation, which affects the expression of certain immune-related genes, being becoming hot spot of explaining the mechanism of autoimmune diseases. This paper reviews the importance of abnormal methylation during the development of common autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and type 1 diabetes, aiming at a better understanding of the pathogenesis of autoimmune diseases and providing new ideas for the treatment of these diseases. PMID:26821302

  13. The relationship between autoimmunity and specific immunotherapy for allergic diseases

    PubMed Central

    Bozek, Andrzej; Kołodziejczyk, Krzysztof; Bednarski, Piotr

    2015-01-01

    The aim of this study was to perform a 20-year post-specific immunotherapy (SIT) observational evaluation for an assessment of any manifestations of autoimmune disease or the appearance of autoantibodies in serum. In total, 1,888 patients (902 women and 986 men) were observed. The mean age of the patients was 34.1±12.4 y at the start of the prospective observation after finishing SIT. New incidences of autoimmune disease and/or the presence of autoantibodies in serum were monitored. The SIT group was compared with control groups consisting of allergic patients who had very received SIT and with non-allergic subjects. There were no significant differences in the autoimmune disease prevalence between the allergic patients with or without SIT. However, significantly higher prevalence of 4 different autoimmune diseases (AID) were observed in the non-allergic patients during the same period. Additionally, the incidence of 8 different autoantibodies was significantly higher in non-allergic patients than in control subjects. Hashimoto disease was the most common autoimmune disease observed. The results of this long-term observational study indicated a lack of a significant prevalence of new instances of autoimmune disease during 20 y of observation post-SIT and at a rate lower than that of non-allergic control subjects, suggesting that SIT is safe in this regard in the long term. PMID:26431066

  14. Vitamin D in systemic and organ-specific autoimmune diseases.

    PubMed

    Agmon-Levin, Nancy; Theodor, Emanuel; Segal, Ramit Maoz; Shoenfeld, Yehuda

    2013-10-01

    Lately, vitamin D has been linked with metabolic and immunological processes, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and upon activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. Epidemiological data underline a strong correlation between poor vitamin D status and higher risk for chronic inflammatory illnesses of various etiologies, including autoimmune diseases. Epidemiological, genetic, and basic studies indicated a potential role of vitamin D in the pathogenesis of certain systemic and organ-specific autoimmune diseases. These studies demonstrate correlation between low vitamin D and prevalence of diseases. In addition, VDRs' polymorphisms observed in some of these autoimmune diseases may further support a plausible pathogenic link. Notably, for some autoimmune disease, no correlation with vitamin D levels could be confirmed. Thus, in the current review we present the body of evidence regarding the plausible roles of vitamin D and VDR's polymorphism in the pathogenesis of autoimmunity. We summarize the data regarding systemic (i.e., systemic lupus erythematosus, rheumatoid arthritis, etc.) and organ-specific (i.e., multiple sclerosis, diabetes mellitus, primary biliary cirrhosis, etc.) autoimmune diseases, in which low level of vitamin D was found comparing to healthy subjects. In addition, we discuss the correlations between vitamin D levels and clinical manifestations and/or activity of diseases. In this context, we address the rational for vitamin D supplementation in patients suffering from autoimmune diseases. Further studies addressing the mechanisms by which vitamin D affects autoimmunity and the proper supplementation required are needed. PMID:23238772

  15. [Autoimmune diseases in type 1A diabetes mellitus].

    PubMed

    Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario Antonio

    2015-08-01

    Type 1A diabetes (DM1A) is an autoimmune disease that comprises 10% of patients with diabetes mellitus. Its frequency is gradually increasing in countries like Mexico. Patients with DM1A commonly have hypothyroidism, Addison disease, celiac disease and less common diseases such as polyglandular syndrome. These diseases are related to susceptibility genes such as HLA, CTLA-4 and PTPN22, which induce central and peripheral immunologic tolerance. This review article emphasizes the importance of searching other autoimmune diseases in patients with DM1A, to improve their prognosis and quality of life.

  16. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

    PubMed Central

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-01-01

    Abstract The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined. We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating. Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN. PMID:26222864

  17. Progression of Liver Disease

    MedlinePlus

    ... You Can Use April May Calendar Liver Lowdown Mar 2014 Calendar of Events In The News Academic ... 2016 Calendar Jan Feb 2016 recipe Liver Lowdown Mar/Apr 2016 Liver Lowdown August 2016 Know Your ...

  18. Occupational exposure to crystalline silica and autoimmune disease.

    PubMed

    Parks, C G; Conrad, K; Cooper, G S

    1999-10-01

    Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures.

  19. Occupational exposure to crystalline silica and autoimmune disease.

    PubMed Central

    Parks, C G; Conrad, K; Cooper, G S

    1999-01-01

    Occupational exposure to silica dust has been examined as a possible risk factor with respect to several systemic autoimmune diseases, including scleroderma, rheumatoid arthritis, systemic lupus erythematosus, and some of the small vessel vasculitidies with renal involvement (e.g., Wegener granulomatosis). Crystalline silica, or quartz, is an abundant mineral found in sand, rock, and soil. High-level exposure to respirable silica dust can cause chronic inflammation and fibrosis in the lung and other organs. Studies of specific occupational groups with high-level silica exposure (e.g., miners) have shown increased rates of autoimmune diseases compared to the expected rates in the general population. However, some clinic- and population-based studies have not demonstrated an association between silica exposure and risk of autoimmune diseases. This lack of effect may be due to the limited statistical power of these studies to examine this association or because the lower- or moderate-level exposures that may be more common in the general population were not considered. Experimental studies demonstrate that silica can act as an adjuvant to nonspecifically enhance the immune response. This is one mechanism by which silica might be involved in the development of autoimmune diseases. Given that several different autoimmune diseases may be associated with silica dust exposure, silica dust may act to promote or accelerate disease development, requiring some other factor to break immune tolerance or initiate autoimmunity. The specific manifestation of this effect may depend on underlying differences in genetic susceptibility or other environmental exposures. PMID:10970168

  20. Perspectives of the relationship between IL-7 and autoimmune diseases.

    PubMed

    Wang, Xiao-Song; Li, Bao-Zhu; Hu, Lin-Feng; Wen, Peng-Fei; Zhang, Min; Pan, Hai-Feng; Ye, Dong-Qing

    2013-12-01

    Interleukin (IL)-7 is one of the IL-2 family cytokines comprised of IL-2, IL-4, IL-7, IL-9, IL-15, as well as IL-21. IL-7 is mainly secreted by stroma cells in primary lymphoid tissues, playing an essential role in the program of T cell development. Recently, studies have revealed that physiological function exerted by immunocytes can be influenced by aberrant IL-7 signaling, which is common in abnormal autoimmunity regulation. There is also increasing evidence that IL-7 is involved in several autoimmune diseases, such as rheumatoid arthritis, type I diabetes, multiple sclerosis and systemic lupus erythematosus, etc. Targeting components in IL-7 signaling pathways may have potential significance for treating numerous autoimmune diseases. In this review, we therefore summarize our current understandings regarding the relationship between IL-7 and autoimmune diseases so as to render more valuable information on this kind of research. PMID:23934388

  1. Screening in liver disease

    PubMed Central

    Poggio, Paolo Del; Mazzoleni, Marzio

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  2. Screening in liver disease.

    PubMed

    Del Poggio, Paolo; Mazzoleni, Marzio

    2006-09-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  3. Novel insights into Tim-4 function in autoimmune diseases.

    PubMed

    Fang, Xin-Yu; Xu, Wang-Dong; Pan, Hai-Feng; Leng, Rui-Xue; Ye, Dong-Qing

    2015-06-01

    T-cell immunoglobulin domain and mucin domain-4 (Tim-4) was first recognized as a costimulatory molecule regulating T-cell activation. Dysregulation of Tim-4 has been found in some autoimmune conditions, particularly in the immune cells. Recently, Tim-4 was found to be critical for regulating T cells, with the ability of inhibiting naïve CD4(+) T cells and Th17 cells, increasing Th2 cell development. Tim-4 can also enhance T cell expansion via linker for activation of T cells, extracellular signal-regulated kinase (ERK) and Protein kinase B (PKB, also known as Akt) signaling pathways. Moreover, the Tim-4 signaling pathway may affect multiple molecular processes in autoimmune diseases. A number of previous studies have demonstrated that Tim-4 influences chronic autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus. In addition, an association between Tim-4 polymorphisms and susceptibility to several autoimmune diseases have been identified, such as RA. Taken together, recent works have indicated that Tim-4 may represent a novel target for the treatment of autoimmune diseases. In this article, we will discuss the Tim-4 function and the therapeutic potential of modulating the Tim-4 in autoimmune diseases.

  4. Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease

    PubMed Central

    Antonelli, A; Fallahi, P; Nesti, C; Pupilli, C; Marchetti, P; Takasawa, S; Okamoto, H; Ferrannini, E

    2001-01-01

    Autoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD+ and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading >3 s.d. higher than the mean value of control I, 10·4% of patients with thyroiditis and 7·7% of Graves' patients were anti-CD38 positive (P = 0·0009 versus 1·8% of control I). Similarly, 13·1% of patients with thyroiditis and 10·5% of Graves' patients had a standardized optical reading >3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0·002 versus 1·2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0·03) and they were more frequent in Graves' patients with ophthalmopathy (P < 0·05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated. PMID:11737057

  5. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

    PubMed

    Matarese, Giuseppe; De Placido, Giuseppe; Nikas, Yorgos; Alviggi, Carlo

    2003-05-01

    Endometriosis is a chronic inflammatory disease, characterized by implantation and growth of endometrial tissue outside the uterine cavity. This disabling condition is considered one of the most frequent diseases in gynecology, affecting 15-20% of women in their reproductive life. Pelvic endometriosis, the most common form of the disease, is associated with increased secretion of pro-inflammatory cytokines, neo-angiogenesis, intrinsic anomalies of the refluxed endometrium and impaired function of cell-mediated natural immunity. Recently, endometriosis has also been considered to be an autoimmune disease, owing to the presence of autoantibodies, the association with other autoimmune diseases and recurrent immune-mediated abortion. These findings are in apparent contradiction with the reduced cell-mediated natural immunity observed during the disease. In this review, we focus on the multiple processes underlying the complex pathogenesis of endometriosis, with particular emphasis on the role played by the immune system with the induction of autoimmunity. PMID:12763528

  6. Recent Advances in the Genetics of Autoimmune Disease

    PubMed Central

    Gregersen, Peter K.; Olsson, Lina M.

    2010-01-01

    Extraordinary technical advances in the field of human genetics over the past few years have catalyzed an explosion of new information about the genetics of human autoimmunity. In particular, the ability to scan the entire genome for common polymorphisms that associate with disease has led to the identification of numerous new risk genes involved in autoimmune phenotypes. Several themes are emerging. Autoimmune disorders have a complex genetic basis; multiple genes contribute to disease risk, each with generally modest effects independently. In addition, it is now clear that common genes underlie multiple autoimmune disorders. There is also heterogeneity among subphenotypes within a disease and across major racial groups. The current crop of genetic associations are only the start of a complete catalog of genetic factors for autoimmunity, and it remains unclear to what extent common variation versus multiple rare variants contribute to disease susceptibility. The current review focuses on recent discoveries within functionally related groups of genes that provide clues to novel pathways of pathogenesis for human autoimmunity. PMID:19302045

  7. Vitamin D endocrine system involvement in autoimmune rheumatic diseases.

    PubMed

    Cutolo, Maurizio; Pizzorni, Carmen; Sulli, Alberto

    2011-12-01

    Vitamin D is synthesized from cholesterol in the skin (80-90%) under the sunlight and then metabolized into an active D hormone in liver, kidney and peripheral immune/inflammatory cells. These endocrine-immune effects include also the coordinated activities of the vitamin D-activating enzyme, 1alpha-hydroxylase (CYP27B1), and the vitamin D receptor (VDR) on cells of the immune system in mediating intracrine and paracrine actions. Vitamin D is implicated in prevention and protection from chronic infections (i.e. tubercolosis), cancer (i.e. breast cancer) and autoimmune rheumatic diseases since regulates both innate and adaptive immunity potentiating the innate response (monocytes/macrophages with antimicrobial activity and antigen presentation), but suppressing the adaptive immunity (T and B lymphocyte functions). Vitamin D has modulatory effects on B lymphocytes and Ig production and recent reports have demonstrated that 1,25(OH)2D3 does indeed exert direct effects on B cell homeostasis. A circannual rhythm of trough vitamin D levels in winter and peaks in summer time showed negative correlation with clinical status at least in rheumatoid arthritis and systemic lupus erythematosus. Recently, the onset of symptoms of early arthritis during winter or spring have been associated with greater radiographic evidence of disease progression at 12 months possibly are also related to seasonal lower vitamin D serum levels.

  8. Dominant Mutations in the Autoimmune Regulator AIRE Are Associated with Common Organ-Specific Autoimmune Diseases.

    PubMed

    Oftedal, Bergithe E; Hellesen, Alexander; Erichsen, Martina M; Bratland, Eirik; Vardi, Ayelet; Perheentupa, Jaakko; Kemp, E Helen; Fiskerstrand, Torunn; Viken, Marte K; Weetman, Anthony P; Fleishman, Sarel J; Banka, Siddharth; Newman, William G; Sewell, W A C; Sozaeva, Leila S; Zayats, Tetyana; Haugarvoll, Kristoffer; Orlova, Elizaveta M; Haavik, Jan; Johansson, Stefan; Knappskog, Per M; Løvås, Kristian; Wolff, Anette S B; Abramson, Jakub; Husebye, Eystein S

    2015-06-16

    The autoimmune regulator (AIRE) gene is crucial for establishing central immunological tolerance and preventing autoimmunity. Mutations in AIRE cause a rare autosomal-recessive disease, autoimmune polyendocrine syndrome type 1 (APS-1), distinguished by multi-organ autoimmunity. We have identified multiple cases and families with mono-allelic mutations in the first plant homeodomain (PHD1) zinc finger of AIRE that followed dominant inheritance, typically characterized by later onset, milder phenotypes, and reduced penetrance compared to classical APS-1. These missense PHD1 mutations suppressed gene expression driven by wild-type AIRE in a dominant-negative manner, unlike CARD or truncated AIRE mutants that lacked such dominant capacity. Exome array analysis revealed that the PHD1 dominant mutants were found with relatively high frequency (>0.0008) in mixed populations. Our results provide insight into the molecular action of AIRE and demonstrate that disease-causing mutations in the AIRE locus are more common than previously appreciated and cause more variable autoimmune phenotypes.

  9. Environmental triggers and epigenetic deregulation in autoimmune disease.

    PubMed

    Javierre, Biola M; Hernando, Henar; Ballestar, Esteban

    2011-12-01

    The study of epigenetic mechanisms in the pathogenesis of autoimmune diseases is receiving unprecedented attention from clinicians and researchers in the field. Autoimmune disorders comprise a wide range of genetically complex diseases, including systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes, and multiple sclerosis. Together they affect a significant proportion of the population and have a great economic impact on public health systems. Epigenetic mechanisms control gene expression and are influenced by external stimuli, linking environment and gene function. A variety of environmental agents, such as viral infection, hormones, certain drugs, and pollutants, have been found to influence the development of autoimmune diseases. On the other hand, there is considerable evidence of epigenetic changes, particularly DNA methylation alterations, in diseases like systemic lupus erythematosus, rheumatoid arthritis, or multiple sclerosis. However, the gap in our understanding between the specific effects of external agents and the influence on epigenetic profiles has not yet been filled. Here we review a number of studies describing epigenetic alterations in autoimmune diseases and a range of environmental factors that influence the development of autoimmune diseases. We also discuss potential mechanisms linking environment and epigenetics, consider the prospects for future epigenetic studies addressing the relationship between environment and epigenetics, and comment on the use of drugs with an epigenetic-reversing effect in the clinical management of these diseases. PMID:22204770

  10. Epigenetics and autoimmune diseases: the X chromosome-nucleolus nexus.

    PubMed

    Brooks, Wesley H; Renaudineau, Yves

    2015-01-01

    Autoimmune diseases occur more often in females, suggesting a key role for the X chromosome. X chromosome inactivation, a major epigenetic feature in female cells that provides dosage compensation of X-linked genes to avoid overexpression, presents special vulnerabilities that can contribute to the disease process. Disruption of X inactivation can result in loss of dosage compensation with expression from previously sequestered genes, imbalance of gene products, and altered endogenous material out of normal epigenetic context. In addition, the human X has significant differences compared to other species and these differences can contribute to the frequency and intensity of the autoimmune disease in humans as well as the types of autoantigens encountered. Here a link is demonstrated between autoimmune diseases, such as systemic lupus erythematosus, and the X chromosome by discussing cases in which typically non-autoimmune disorders complicated with X chromosome abnormalities also present lupus-like symptoms. The discussion is then extended to the reported spatial and temporal associations of the inactive X chromosome with the nucleolus. When frequent episodes of cellular stress occur, the inactive X chromosome may be disrupted and inadvertently become involved in the nucleolar stress response. Development of autoantigens, many of which are at least transiently components of the nucleolus, is then described. Polyamines, which aid in nucleoprotein complex assembly in the nucleolus, increase further during cell stress, and appear to have an important role in the autoimmune disease process. Autoantigenic endogenous material can potentially be stabilized by polyamines. This presents a new paradigm for autoimmune diseases: that many are antigen-driven and the autoantigens originate from altered endogenous material due to episodes of cellular stress that disrupt epigenetic control. This suggests that epigenetics and the X chromosome are important aspects of autoimmune

  11. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

    PubMed

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression. PMID:27493014

  12. Interleukin-22: a likely target for treatment of autoimmune diseases

    PubMed Central

    Yang, Xuyan; Zheng, Song Guo

    2014-01-01

    Interleukin -22 (IL-22) is a member of IL-10 family cytokines that is produced by many different types of lymphocytes including both those of the innate and adaptive immune system. This includes activated T cells, most notably Th17 and Th22 cells, and NK cells, γδ T cells, LTi cells and LTi-like cells. IL-22 mediates its effects via the IL-22-IL-22R complex and subsequent Janus Kinase-signal transduces and activators transcription (JAK-STAT) signaling pathway. Recently accumulated evidence has indicated that IL-22 also plays an important role in the pathogenesis of many autoimmune diseases. In this review, we discuss the recent findings and advancement of the role for IL-22 in several autoimmune diseases, such as psoriasis, rheumatoid arthritis (RA), hepatitis, graft versus host disease (GHVD) and allergic diseases, implicating that target IL-22 may have a therapeutic potential in those autoimmune diseases. PMID:24418299

  13. Liver transplantation for Wilson's disease.

    PubMed

    Schilsky, Michael L

    2014-05-01

    Although Wilsons's disease (WD) may be treated with copper chelation (to remove copper) or zinc salts (to prevent absorption) to alleviate or prevent symptom development in most patients, there are WD patients for whom medical therapy is inadequate and survival would be unlikely without liver transplantation. Liver transplantation is indicated for the ∼5% of WD patients with acute liver failure as the first presentation of disease, most commonly in the second decade of life, or those who present with end-stage liver disease and severe hepatic insufficiency, most commonly in the third and fourth decades. Liver transplantation restores normal biliary copper excretion (thereby preventing disease recurrence) and promotes removal of copper from extrahepatic sites. Outcomes of liver transplantation for WD are excellent, including both cadaveric and living donors.

  14. Folate, Alcohol, and Liver Disease

    PubMed Central

    Medici, Valentina; Halsted, Charles H.

    2013-01-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  15. Coagulation and Autoimmunity in Scleroderma Interstitial Lung Disease

    PubMed Central

    Ludwicka-Bradley, Anna; Silver, Richard M.; Bogatkevich, Galina S.

    2010-01-01

    Objectives Interstitial lung disease in systemic sclerosis (SSc-ILD) is often an irreversible and progressive fibrosing process that now is the leading cause of scleroderma-related deaths. In this review we present our current understanding of the role played by coagulation and particularly by thrombin in autoimmune-mediated tissue injury and fibrosis, mainly as it relates to SSc-ILD. Methods We used PubMed to search for articles published up to October 2010 for keywords referring to autoimmunity, coagulation, pulmonary fibrosis, and scleroderma. Results SSc-ILD is an autoimmune disease associated with lymphocyte activation and release of various cytokines and growth factors. The production of autoantibodies is a central feature in SSc. Activation of the coagulation cascade with release of thrombin is 1 of the earliest events following tissue injury. Thrombin contributes to autoimmune responses by activating of pathogenic Th2 lymphocyte profile in SSc. Thrombin also modulates tissue repair responses, stimulates transformation of epithelial cells, endothelial cells, and fibroblasts into myofibroblast phenotype, and induces secretion of several pro-immune and profibrotic factors, which serve as antigens for pathogenic autoantibodies production in SSc-ILD. Conclusions The identification of links between autoimmunity and coagulation would provide new insights into the pathogenesis of pulmonary fibrosis associated with autoimmune diseases and further acknowledge the importance of thrombin in the development of SSc-ILD. PMID:21168185

  16. Asialoglycoprotein receptor (ASGPR): a peculiar target of liver-specific autoimmunity.

    PubMed

    Roggenbuck, Dirk; Mytilinaiou, Maria G; Lapin, Sergey V; Reinhold, Dirk; Conrad, Karsten

    2012-12-01

    Asialoglycoprotein receptor (ASGPR) autoantibodies have been considered specific markers of autoimmune hepatitis (AIH). The exact mechanisms responsible for the development of these autoantibodies and leading to autoimmunity to this peculiar liver receptor remain elusive. Furthermore, loss of T cell tolerance to ASGPR has been demonstrated in patients with AIH, but it is poorly understood whether such liver-specific T cell responses bear a pathogenic potential and/or participate in the precipitation of AIH. Newly developed enzyme-linked immunosorbent assays have led to the investigation of the sensitivity and specificity of anti-ASGPR antibodies for AIH. The present review provides an overview of the diagnostic and clinical relevance of anti-ASGPR antibodies. A thorough investigation of the autoreactivity against ASGPR may assist efforts to understand liver autoimmunity in susceptible individuals.

  17. Transient Expression of Transgenic IL-12 in Mouse Liver Triggers Unremitting Inflammation Mimicking Human Autoimmune Hepatitis.

    PubMed

    Gil-Farina, Irene; Di Scala, Marianna; Salido, Eduardo; López-Franco, Esperanza; Rodríguez-García, Estefania; Blasi, Mercedes; Merino, Juana; Aldabe, Rafael; Prieto, Jesús; Gonzalez-Aseguinolaza, Gloria

    2016-09-15

    The etiopathogenesis of autoimmune hepatitis (AIH) remains poorly understood. In this study, we sought to develop an animal model of human AIH to gain insight into the immunological mechanisms driving this condition. C57BL/6 mice were i.v. injected with adeno-associated viral vectors encoding murine IL-12 or luciferase under the control of a liver-specific promoter. Organ histology, response to immunosuppressive therapy, and biochemical and immunological parameters, including Ag-specific humoral and cellular response, were analyzed. Mechanistic studies were carried out using genetically modified mice and depletion of lymphocyte subpopulations. Adeno-associated virus IL-12-treated mice developed histological, biochemical, and immunological changes resembling type 1 AIH, including marked and persistent liver mononuclear cell infiltration, hepatic fibrosis, hypergammaglobulinemia, anti-nuclear and anti-smooth muscle actin Abs, and disease remission with immunosuppressive drugs. Interestingly, transgenic IL-12 was short-lived, but endogenous IL-12 expression was induced, and both IL-12 and IFN-γ remained elevated during the entire study period. IFN-γ was identified as an essential mediator of liver damage, and CD4 and CD8 T cells but not NK, NKT, or B cells were essential executors of hepatic injury. Furthermore, both MHC class I and MHC class II expression was upregulated at the hepatocellular membrane, and induction of autoreactive liver-specific T cells was detected. Remarkably, although immunoregulatory mechanisms were activated, they only partially mitigated liver damage. Thus, low and transient expression of transgenic IL-12 in hepatocytes causes loss of tolerance to hepatocellular Ags, leading to chronic hepatitis resembling human AIH type 1. This model provides a practical tool to explore AIH pathogenesis and novel therapies. PMID:27511737

  18. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  19. Air pollution in autoimmune rheumatic diseases: a review.

    PubMed

    Farhat, Sylvia C L; Silva, Clovis A; Orione, Maria Angelica M; Campos, Lucia M A; Sallum, Adriana M E; Braga, Alfésio L F

    2011-11-01

    Air pollution consists of a heterogeneous mixture of gasses and particles that include carbon monoxide, nitrates, sulfur dioxide, ozone, lead, toxic by-product of tobacco smoke and particulate matter. Oxidative stress and inflammation induced by inhaled pollutants may result in acute and chronic disorders in the respiratory system, as well as contribute to a state of systemic inflammation and autoimmunity. This paper reviews the mechanisms of air contaminants influencing the immune response and autoimmunity, and it focuses on studies of inhaled pollutants triggering and/or exacerbating rheumatic diseases in cities around the world. Remarkably, environmental factors contribute to the onset of autoimmune diseases, especially smoking and occupational exposure to silica in rheumatoid arthritis and systemic lupus erythematosus. Other diseases such as scleroderma may be triggered by the inhalation of chemical solvents, herbicides and silica. Likewise, primary vasculitis associated with anti-neutrophil cytoplasmic antibody (ANCA) may be triggered by silica exposure. Only few studies showed that air pollutants could trigger or exacerbate juvenile idiopathic arthritis and systemic lupus erythematosus. In contrast, no studies of tropospheric pollution triggering inflammatory myopathies and spondyloarthropathies were carried out. In conclusion, air pollution is one of the environmental factors involved in systemic inflammation and autoimmunity. Further studies are needed in order to evaluate air pollutants and their potentially serious effects on autoimmune rheumatic diseases and the mechanisms involved in the onset and the exacerbation of these diseases.

  20. [Wilson's disease: clinical spectrum of liver disease].

    PubMed

    Ochoa Palominos, Alejandra; Ibáñez Samaniego, Luis; Catalina Rodríguez, María-Vega; Pajares Díaz, José; Clemente Ricote, Gerardo

    2013-02-01

    Wilson's disease is a hereditary autosomal recessive disorder of copper metabolism,characterized by copper accumulation in the liver and brain. This rare entity, which has a broad clinical spectrum, is often difficult to diagnose and should therefore always be suspected in patients with liver disease of unclear cause. We describe two types of manifestation of liver disease in two patients; the first developed fulminant hepatic failure requiring urgent liver transplantation and the second showed advanced chronic liver disease and received standard medical treatment. The objective of this clinical observation is to analyze the diagnosis of Wilson's disease in two patients with distinct onset, illustrating the broad clinical spectrum of the disease, and its treatment.

  1. Prognostic Implications of Antibodies to Soluble Liver Antigen in Autoimmune Hepatitis

    PubMed Central

    Chen, Zhi-Xian; Shao, Jian-Guo; Shen, Yi; Zhang, Jian; Hua, Yu; Wang, Lu-Jun; Qin, Gang

    2015-01-01

    Abstract Prognostic evaluation is important for the management of patients with autoimmune hepatitis (AIH). Although some autoantibodies have been associated with disease activity and outcomes, the implication of antibodies to soluble liver antigen (anti-SLA) remains controversial. To conduct a meta-analysis of observational studies which addressed differences in clinical characteristics by anti-SLA status in patients with AIH. Three databases PUBMED, EMBASE, and OVID were systemically searched up to January 2015 using the terms “soluble liver antigen” or “liver-pancreas antigen” and “autoimmune hepatitis” with restriction to English-language. Studies were included if at least 50 patients with objective diagnosis of AIH were enrolled, anti-SLA detection was performed for the patients, and prognostic outcomes and/or disease severity were reported. Two investigators independently reviewed retrieved literature and evaluated eligibility. Discrepancy was resolved by discussion and a third investigator. Quality of included studies was evaluated using Newcastle-Ottawa Quality Assessment Scale (NOS). Data were pooled using fixed-effect or random-effect models. Prognostic outcomes included death from hepatic failure or requirement for liver transplantation, and responses to immunosuppressive therapy regarding remission or relapse. Results were combined on the odds ratio (OR) or standardized mean difference (SMD) scales. Eight studies were enrolled in this study, involving a total of 1297 AIH patients among whom 195 with anti-SLA. Pooled serum AST levels tended to be lower in anti-SLA seropositive patients. The presence of anti-SLA conferred 3.1-fold increased risk of hepatic death in AIH patients. The remission rates were comparable between anti-SLA seropositive and seronegative AIH patients, while anti-SLA positivity was associated with nearly 2-fold increased risk of relapse after drug withdrawal. Human leukocyte antigen (HLA) allotype DR3 was positively

  2. Intestinal microbiota in liver disease.

    PubMed

    Haque, Tanvir R; Barritt, A Sidney

    2016-02-01

    The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation.

  3. Is Tourette's syndrome an autoimmune disease?

    PubMed

    Hoekstra, P J; Kallenberg, C G M; Korf, J; Minderaa, R B

    2002-01-01

    We provide a review of recent research findings which support the involvement of autoimmunity in childhood-onset tic disorders, in particular the presence of antineuronal autoantibodies, D8/17 B lymphocyte overexpression, a marker of chorea associated with streptococcal infection, and possible beneficial effects of immunomodulatory intervention. One of the most controversial areas in this field is the validity of the proposed PANDAS concept. Some researchers have delineated a putatively unique subgroup of patients, from the spectrum of illness encompassing Tourette's syndrome and obsessive-compulsive disorder (OCD), whose tics and obsessive-compulsive symptoms are shown to arise in response to beta-hemolytic streptococcal infections. They designated it by the term pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). Herein we additionally present pros and cons concerning the concept of PANDAS. Finally, recommendations for future research directions are given.

  4. The role of AIRE in human autoimmune disease.

    PubMed

    Akirav, Eitan M; Ruddle, Nancy H; Herold, Kevan C

    2011-01-01

    The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease, hypoparathyroidism and chronic mucocutaneous candidiasis. This Review describes the process of positive and negative selection of developing T cells in the thymus and the role of AIRE as a regulator of peripheral antigen presentation. Furthermore, it addresses how mutations of this gene lead to the failure to eliminate autoreactive T cells, which can lead to clinical autoimmune syndromes. PMID:21102544

  5. Pink Light on Mitochondria in Autoimmunity and Parkinson Disease.

    PubMed

    Mantegazza, Adriana R; Marks, Michael S

    2016-07-12

    Mitochondrial dysfunction and T cell autoimmunity have been independently implicated in Parkinson disease pathogenesis. In a recent publication in Cell, Matheoud et al. (2016) link them by describing a new mechanism, activated in familial forms of Parkinson disease, in which mitochondrial proteins are processed for recognition by CD8+ T cells. PMID:27411006

  6. Peripheral blood T-lymphocyte subsets in autoimmune thyroid disease.

    PubMed

    Covas, M I; Esquerda, A; García-Rico, A; Mahy, N

    1992-01-01

    Interest in T-lymphocyte subsets has arisen because of their involvement in the autoimmune process. Contradictory results have been published in the literature about the number of peripheral blood lymphocyte subsets in autoimmune diseases. In order to investigate the number and distribution of peripheral blood lymphocyte subsets in autoimmune thyroid disease, the levels of total T-lymphocytes (CD3), T-helper (CD4) and T-suppressor/cytotoxic (CD8) lymphocytes were determined in 44 patients with Graves' disease (1), multinodular goiter (2) and Hashimoto's thyroiditis (3). All patients had high levels of antithyroglobulin and thyroid antiperoxidase (antimicrosomal) antibodies. The T subset levels were related to the functional thyroid status, measured as serum free thyroxine (FT4) and thyrotropin (TSH). Our data show the existence of a strong influence of functional status on CD3, CD4 and CD8 levels, as reflected in the significant correlations obtained with FT4 (negative) and TSH (positive). A significant decrease in all populations was observed in Graves' disease hyperthyroid patients. A decrease in the CD4/CD8 ratio in Hashimoto's thyroiditis hypothyroid patients was observed, in contrast to an increase in the ratio in autoimmune hyperthyroid patients. This points to the CD4/CD8 ratio as a differential characteristic between the two autoimmune (hypothyroid and hyperthyroid) entities, independent of free thyroxine levels. No significant correlation was found between antithyroid antibody levels and peripheral blood T-lymphocyte subsets or serum levels of FT4 and TSH.

  7. Chronic Liver Disease and Hispanic Americans

    MedlinePlus

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While the ...

  8. Emerging role of Interleukin-22 in autoimmune diseases

    PubMed Central

    Pan, Hai-Feng; Li, Xiang-Pei; Zheng, Song Guo; Ye, Dong-Qing

    2014-01-01

    Interleukin-22 (IL-22) is an IL-10 family cytokine member that was recently discovered to be mainly produced by Th17 cells. Previous studies have indicated the importance of IL-22 in host defense against Gram-negative bacterial organisms (in gut and lung). Recently, there is emerging evidence that IL-22 is involved in the development and pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), multiple sclerosis (MS), Sjögren’s syndrome (SS) and psoriasis. Therapeutics targeting IL-22 therefore may have promise for treating various autoimmune diseases. In this review, we discuss the recent progression of the involvement of IL-22 in the development and pathogenesis of autoimmune diseases, as well as its clinical implications and therapeutic potential. PMID:22906768

  9. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.

    PubMed

    Bonney, Kevin M; Engman, David M

    2015-06-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors-autoimmunity-has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease.

  10. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3475920

  11. Dendritic cells in autoimmune thyroid disease.

    PubMed

    Kabel, P J; Voorbij, H A; van der Gaag, R D; Wiersinga, W M; de Haan, M; Drexhage, H A

    1987-01-01

    Dendritic cells form a morphologically distinct class of cells characterized by shape, reniform nucleus, absent to weak acid-phosphatase activity and strong Class II MHC determinant positivity. Functionally they are the most efficient cells in antigen presentation to T-lymphocytes which indicates their role in the initiation of an immune response. Using immunehistochemical techniques we studied the presence of dendritic cells in normal Wistar rat and human thyroids, in thyroids of BBW rats developing thyroid autoimmunity and in Graves' goitres. Dendritic cells could be identified in all thyroids studied and were positioned underneath the thyrocytes in between the follicles. Skin dendritic cells travel via lymphatics to draining lymph nodes, thus forming an antigen presenting cell system. It is likely that a similar cell system exists on the level of the thyroid for dendritic cells have also been detected in thyroid draining lymph nodes. In normal thyroid tissue of both human and rat dendritic cells were relatively scarce. During the initial phases of the thyroid autoimmune response in the BBW rat (before the appearance of Tg-antibodies in the circulation) numbers of thyroid dendritic cells increased. Intrathyroidal T-helper cells, B-cells or plasma cells could not be found. The thyroid draining lymph node contained large numbers of plasma cells. During the later stages of the thyroid autoimmune response in the BB/W rat (after the appearance of Tg-antibodies in the circulation) and in Graves' goitres dendritic cells were not only present in high number, but 20-30% were seen in contact with now-present intrathyroidal T-helper lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Age impact on autoimmune thyroid disease in females

    NASA Astrophysics Data System (ADS)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  13. Family history of autoimmune thyroid disease and childhood acute leukemia.

    PubMed

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  14. Biomarkers in Pediatric Liver Disease.

    PubMed

    Kyrana, Eirini; Fitzpatrick, Emer; Dhawan, Anil

    2016-01-01

    The chronic nature of liver diseases in children and adults merits close follow-up for disease progression and/or treatment evaluation. Disease progression involves injury to liver cells resulting in cell death, varying degrees of inflammation, steatosis depending on the insult, oxidative stress, and eventually fibrosis and cirrhosis unless the process is modified with treatment or spontaneous recovery. Inflammation, cell death, and fibrosis are the three major processes that determine the outcome of liver disease irrespective of the etiology. Markers to measure the activity or status of these parameters in a dynamic way, particularly via noninvasive methods, are urgently required. In this chapter, we summarize recent advances in the identification of biomarkers of liver diseases: biomarkers corresponding to inflammation, cell death, fibrosis, and the development of malignancy.

  15. Nitric oxide in liver diseases.

    PubMed

    Iwakiri, Yasuko; Kim, Moon Young

    2015-08-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling - nitrated fatty acids (NO2-FAs) and S-guanylation - and conclude with suggestions for future directions in NO-related studies on the liver. PMID:26027855

  16. NITRIC OXIDE IN LIVER DISEASES

    PubMed Central

    Iwakiri, Yasuko; Kim, Moon Young

    2015-01-01

    Nitric oxide (NO) and its derivatives play important roles in the physiology and pathophysiology of the liver. Despite its diverse and complicated roles, certain patterns of the effect of NO on the pathogenesis and progression of liver diseases are observed. In general, NO derived from endothelial NO synthase (eNOS) in liver sinusoidal endothelial cells (LSECs) is protective against disease development, while inducible NOS (iNOS)-derived NO contributes to pathological processes. This review addresses the roles of NO in the development of various liver diseases with a focus on recently published articles. We present here two recent advances in understanding NO-mediated signaling, nitrated fatty acids and S-guanylation, and conclude with suggestions on future directions of NO-related studies on the liver. PMID:26027855

  17. The use of hematopoietic stem cells in autoimmune diseases.

    PubMed

    Ben Nasr, Moufida; Bassi, Roberto; Usuelli, Vera; Valderrama-Vasquez, Alessandro; Tezza, Sara; D'Addio, Francesca; Fiorina, Paolo

    2016-06-01

    Hematopoietic stem cells (HSCs) have been shown recently to hold much promise in curing autoimmune diseases. Newly diagnosed Type 1 diabetes individuals have been successfully reverted to normoglycemia by administration of autologous HSCs in association with a nonmyeloablative regimen (antithymocyte globulin + cyclophasmide). Furthermore, recent trials reported positive results by using HSCs in treatment of systemic sclerosis, multiple sclerosis and rheumatoid arthritis as well. Early data suggested that HSCs possess immunological properties that may be harnessed to alleviate the symptoms of individuals with autoimmune disorders and possibly induce remission of autoimmune diseases. Mechanistically, HSCs may facilitate the generation of regulatory T cells, may inhibit the function of autoreactive T-cell function and may reshape the immune system. PMID:27165670

  18. Modulation by Melatonin of the Pathogenesis of Inflammatory Autoimmune Diseases

    PubMed Central

    Lin, Gu-Jiun; Huang, Shing-Hwa; Chen, Shyi-Jou; Wang, Chih-Hung; Chang, Deh-Ming; Sytwu, Huey-Kang

    2013-01-01

    Melatonin is the major secretory product of the pineal gland during the night and has multiple activities including the regulation of circadian and seasonal rhythms, and antioxidant and anti-inflammatory effects. It also possesses the ability to modulate immune responses by regulation of the T helper 1/2 balance and cytokine production. Autoimmune diseases, which result from the activation of immune cells by autoantigens released from normal tissues, affect around 5% of the population. Activation of autoantigen-specific immune cells leads to subsequent damage of target tissues by these activated cells. Melatonin therapy has been investigated in several animal models of autoimmune disease, where it has a beneficial effect in a number of models excepting rheumatoid arthritis, and has been evaluated in clinical autoimmune diseases including rheumatoid arthritis and ulcerative colitis. This review summarizes and highlights the role and the modulatory effects of melatonin in several inflammatory autoimmune diseases including multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus, and inflammatory bowel disease. PMID:23727938

  19. Subclasses of immunoglobulins and autoantibodies in autoimmune diseases.

    PubMed

    Outschoorn, I; Rowley, M J; Cook, A D; Mackay, I R

    1993-01-01

    The differing capacity of subclasses of IgG to bind to protein A and protein G was used in a sequential affinity purification procedure to examine immunoglobulin isotypes and subclasses in autoimmune disease. The utility of the procedure is that affinity-purified fractions containing particular isotypes and subclasses of immunoglobulin can be analyzed for their content of autoantibodies using standard techniques. For each of four autoimmune diseases studied, chronic active hepatitis, Sjogren's syndrome, primary biliary cirrhosis, and rheumatoid arthritis, there were characteristic protein elution profiles and the various disease-specific autoantibodies showed preferential distributions among the isotypes and subclasses. Moreover there was not an absolute correlation between an increased level of a particular subclass and the occurrence of antibodies of that subclass. The occurrence of highly disease-specific immunoglobulin subclass profiles suggests that the hypergammaglobulinemia associated with autoimmunity cannot be attributed entirely to polyclonal B-cell activation. Rather, there are disease-specific alterations in isotype subclass switching which may reflect different cytokine-dependent influences on autoimmune B cells and their products.

  20. Immunoglobulin G4-related disease: autoimmune pancreatitis and extrapancreatic manifestations*

    PubMed Central

    Fernandes, Daniel Alvarenga; Kido, Ricardo Yoshio Zanetti; Barros, Ricardo Hoelz de Oliveira; Martins, Daniel Lahan; Penachim, Thiago José; Caserta, Nelson Marcio Gomes

    2016-01-01

    We present a case of immunoglobulin G4 (IgG4)-related disease with pancreatic and extrapancreatic involvement, including the biliary and renal systems. Given the importance of imaging methods for the diagnosis of IgG4-related disease and its differentiation from pancreatic adenocarcinoma, we emphasize important abdominal computed tomography and magnetic resonance imaging findings related to this recently recognized systemic autoimmune disease. PMID:27141136

  1. The role of parvovirus B19 in the pathogenesis of autoimmunity and autoimmune disease.

    PubMed

    Kerr, Jonathan R

    2016-04-01

    Human parvovirus B19 is a single-stranded DNA virus which preferentially targets the erythroblasts in the bone marrow. B19 infection commonly causes erythema infectiosum, arthralgia, fetal death, transient aplastic crisis in patients with shortened red cell survival, and persistent infection in people who are immunocompromised. Less common clinical manifestations include atypical skin rashes, neurological syndromes, cardiac syndromes, and various cytopenias. B19 infection has also been associated with development of a variety of different autoimmune diseases, including rheumatological, neurological, neuromuscular, cardiovascular, haematological, nephrological and metabolic. Production of a variety of autoantibodies has been demonstrated to occur during B19 infection and these have been shown to be key to the pathogenesis of the particular disease process in a significant number of cases, for example, production of rheumatoid factor in cases of B19-associated rheumatoid arthritis and production of anti-glutamic acid decarboxylase (GAD) in patients with B19-associated type 1 diabetes mellitus. B19 infection has also been associated with the development of multiple autoimmune diseases in 12 individuals. Documented mechanisms in B19-associated autoimmunity include molecular mimicry (IgG antibody to B19 proteins has been shown to cross react with a variety of recognised human autoantigens, including collagen II, keratin, angiotensin II type 1 receptor, myelin basic protein, cardiolipin, and platelet membrane glycoprotein IIb/IIIa), B19-induced apoptosis with presentation of self-antigens to T lymphocytes, and the phospholipase activity of the B19 unique VP1 protein. PMID:26644521

  2. Toward molecular pathogenesis of an autoimmune disease: Refined genetic mapping of autoimmune polyglandular disease type I (APECED)

    SciTech Connect

    Aaltonen, J.; Bjoerses, P.; Peltonen, L.

    1994-09-01

    Autoimmune reactions encoupled to many human diseases are still only partially understood. Unravelling the molecular pathogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect individual components in the molecular background of abnormal immune response. One such genetic disorder is autosomal recessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, MIM 240300). The disease is especially enriched in the genetically isolated population of Finland and we have assigned the APECED locus to human chromosome 21q22.3 in 14 Finnish families by linkage analyses. The best positional lod score of 6.49 was observed with marker D21S49. Based on the history of the Finns, the gene pool of this population clearly demonstrates the consequences of a founder effect and consequent isolation. In the Finnish population, we can take advantage of linkage disequilibrium and allelic association studies to more precisely define the critical DNA region for our disease gene of interest than would be possible by linkage analyses alone. We are now able to define the chromosomal region of interest between two flanking markers locating 1 cM apart. Linkage disequilibrium is observed with three of the markers used in the analyses and this suggests a distance of less than 500 kb to the disease locus, well approachable with molecular cloning techniques. Overlapping YAC and cosmid clones spanning our region of interest will facilitate the cloning of APECED gene in the near future.

  3. Cannabinoids and autoimmune diseases: A systematic review.

    PubMed

    Katchan, Valeria; David, Paula; Shoenfeld, Yehuda

    2016-06-01

    Cannabinoids have shown to have a variety effects on body systems. Through CB1 and CB2 receptors, amongst other, they exert an effect by modulating neurotransmitter and cytokine release. Current research in the role of cannabinoids in the immune system shows that they possess immunosuppressive properties. They can inhibit proliferation of leucocytes, induce apoptosis of T cells and macrophages and reduce secretion of pro-inflammatory cytokines. In mice models, they are effective in reducing inflammation in arthritis, multiple sclerosis, have a positive effect on neuropathic pain and in type 1 diabetes mellitus. They are effective as treatment for fibromyalgia and have shown to have anti-fibrotic effect in scleroderma. Studies in human models are scarce and not conclusive and more research is required in this field. Cannabinoids can be therefore promising immunosuppressive and anti-fibrotic agents in the therapy of autoimmune disorders. PMID:26876387

  4. Research Areas: Liver Disease

    MedlinePlus

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: New medication shows promise against liver fibrosis ... linked to biliary atresia in newborn animals Support Research NIDDK invests in basic, clinical and translational research ...

  5. Alcoholic liver disease

    MedlinePlus

    ... weight loss Nausea or belly pain Small, red spider-like blood vessels on the skin As liver ... result of too much fluid Reddened palms Red spider-like blood vessels on the skin Small testicles ...

  6. Autologous hematopoietic stem cell transplantation for autoimmune diseases.

    PubMed

    Gratwohl, A; Passweg, J; Bocelli-Tyndall, C; Fassas, A; van Laar, J M; Farge, D; Andolina, M; Arnold, R; Carreras, E; Finke, J; Kötter, I; Kozak, T; Lisukov, I; Löwenberg, B; Marmont, A; Moore, J; Saccardi, R; Snowden, J A; van den Hoogen, F; Wulffraat, N M; Zhao, X W; Tyndall, A

    2005-05-01

    Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

  7. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  8. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children

    PubMed Central

    Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R.

    2016-01-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation.

  9. Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

    PubMed

    Bolia, Rishi; Chong, Sze Yee; Coleman, Lee; MacGregor, Duncan; Hardikar, Winita; Oliver, Mark R

    2016-07-01

    We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation. PMID:27622194

  10. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  11. [Autoimmune hepatitis].

    PubMed

    Marcais, O; Larrey, D

    1994-01-01

    Acute and chronic autoimmune hepatitis are uncommon inflammatory liver diseases, mainly occurring in young women, in association with hypergammaglobulinemia and serum autoantibodies. Different types have been described: type 1 characterized by anti-smooth muscle and anti-nuclear antibodies; type 2 characterized by anti-LKM1 antibodies; type 3 characterized by anti-SLA antibodies. Other types, still not clearly defined, may exist. Autoimmune hepatitis are associated with HLA A1 B8 DR3 and HLA DR4. Without any treatment, the disease leads to cirrhosis and, uncommonly, to fulminant hepatitis. Large doses of corticosteroids usually allow to control the disease. Relapse of hepatitis is frequent after corticosteroid withdrawal. Concomitant administration of immunosuppressive agents such as azathioprine allows to reduce corticosteroid dosage and contributes to maintain the remission of the disease. Liver transplantation may be indicated in cases of severe cirrhosis or fulminant hepatitis.

  12. Why are women predisposed to autoimmune rheumatic diseases?

    PubMed Central

    2009-01-01

    The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes - both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma. PMID:19863777

  13. AAV-IL-22 modifies liver chemokine activity and ameliorates portal inflammation in murine autoimmune cholangitis.

    PubMed

    Hsueh, Yu-Hsin; Chang, Yun-Ning; Loh, Chia-En; Gershwin, M Eric; Chuang, Ya-Hui

    2016-01-01

    There remain significant obstacles in developing biologics to treat primary biliary cholangitis (PBC). Although a number of agents have been studied both in murine models and human patients, the results have been relatively disappointing. IL-22 is a member of the IL-10 family and has multiple theoretical reasons for predicting successful usage in PBC. We have taken advantage of an IL-22 expressing adeno-associated virus (AAV-IL-22) to address the potential role of IL-22 in not only protecting mice from autoimmune cholangitis, but also in treating animals with established portal inflammation. Using our established mouse model of 2-OA-OVA immunization, including α-galactosylceramide (α-GalCer) stimulation, we treated mice both before and after the onset of clinical disease with AAV-IL-22. Firstly, AAV-IL-22 treatment given prior to 2-OA-OVA and α-GalCer exposure, i.e. before the onset of disease, significantly reduces the portal inflammatory response, production of Th1 cytokines and appearance of liver fibrosis. It also reduced the liver lymphotropic chemokines CCL5, CCL19, CXCL9, and CXCL10. Secondly, and more importantly, therapeutic use of AAV-IL-22, administered after the onset of disease, achieved a greater hurdle and significantly improved portal pathology. Further the improvements in inflammation were negatively correlated with levels of CCL5 and CXCL10 and positively correlated with levels of IL-22. In conclusion, we submit that the clinical use of IL-22 has a potential role in modulating the inflammatory portal process in patients with PBC.

  14. [Metabolic disorders and nutritional status in autoimmune thyroid diseases].

    PubMed

    Kawicka, Anna; Regulska-Ilow, Bożena; Regulska-Ilow, Bożena

    2015-01-02

    In recent years, the authors of epidemiological studies have documented that autoimmune diseases are a major problem of modern society and are classified as diseases of civilization. Autoimmune thyroid diseases (ATDs) are caused by an abnormal immune response to autoantigens present in the thyroid gland - they often coexist with other autoimmune diseases. The most common dysfunctions of the thyroid gland are hypothyroidism, Graves-Basedow disease and Hashimoto's disease. Hashimoto's thyroiditis can be the main cause of primary hypothyroidism of the thyroid gland. Anthropometric, biochemical and physicochemical parameters are used to assess the nutritional status during the diagnosis and treatment of thyroid diseases. Patients with hypothyroidism are often obese, whereas patients with hyperthyroidism are often afflicted with rapid weight loss. The consequence of obesity is a change of the thyroid hormones' activity; however, weight reduction leads to their normalization. The activity and metabolic rate of thyroid hormones are modifiable. ATDs are associated with abnormalities of glucose metabolism and thus increased risk of developing diabetes mellitus type 1 and type 2. Celiac disease (CD) also increases the risk of developing other autoimmune diseases. Malnutrition or the presence of numerous nutritional deficiencies in a patient's body can be the cause of thyroid disorders. Coexisting deficiencies of such elements as iodine, iron, selenium and zinc may impair the function of the thyroid gland. Other nutrient deficiencies usually observed in patients suffering from ATD are: protein deficiencies, vitamin deficiencies (A, C, B6, B5, B1) and mineral deficiencies (phosphorus, magnesium, potassium, sodium, chromium). Proper diet helps to reduce the symptoms of the disease, maintains a healthy weight and prevents the occurrence of malnutrition. This article presents an overview of selected documented studies and scientific reports on the relationship of metabolic

  15. Autologous hematopoietic stem cell transplantation in autoimmune diseases.

    PubMed

    Annaloro, Claudio; Onida, Francesco; Lambertenghi Deliliers, Giorgio

    2009-12-01

    The term 'autoimmune diseases' encompasses a spectrum of diseases whose clinical manifestations and, possibly, biological features vary widely. The results of conventional treatment are considered unsatisfactory in aggressive forms, with subsets of patients having short life expectancies. Relying on wide experimental evidence and more feeble clinical data, some research groups have used autologous hematopoietic stem cell transplantation (HSCT) in the most disabling autoimmune diseases with the aim of resetting the patient's immune system. Immunoablative conditioning regimens are preferred over their myeloablative counterparts, and some form of in vivo and/or ex vivo T-cell depletion is generally adopted. Despite 15 years' experience, published controlled clinical trials are still lacking, with the evidence so far available coming from pilot studies and registry surveys. In multiple sclerosis, clinical improvement, or at least lasting disease stabilization, can be achieved in the majority of the patients; nevertheless, the worst results are observed in patients with progressive disease, where no benefit can be expected from conventional therapy. Concerning rheumatologic diseases, wide experience has been acquired in systemic sclerosis, with long-term improvements in cutaneous disease being frequently reported, although visceral involvement remains unchanged at best. Autografting has proved to be barely effective in rheumatoid arthritis and quite toxic in juvenile idiopathic arthritis, whereas it leads to clinical remission and the reversal of visceral impairment in the majority of patients with systemic lupus erythematosus. A promising indication is Crohn's disease, in which long-term endoscopic remission is frequently observed. Growing experience with autologous HCST in autoimmune diseases has progressively reduced concerns about transplant-related mortality and secondary myelodysplasia/leukemia. Therefore, a sustained complete remission seems to be within the

  16. Induction of Regulatory t Cells by Low Dose il2 in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-04-18

    Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus; Psoriasis; Behcet's Disease; Wegener's Granulomatosis; Takayasu's Disease; Crohn's Disease; Ulcerative Colitis; Autoimmune Hepatitis; Sclerosing Cholangitis

  17. Autoimmune hepatitis, one disease with many faces: Etiopathogenetic, clinico-laboratory and histological characteristics

    PubMed Central

    Gatselis, Nikolaos K; Zachou, Kalliopi; Koukoulis, George K; Dalekos, George N

    2015-01-01

    Autoimmune hepatitis (AIH) is an unresolving progressive liver disease of unknown etiology characterized by hypergammaglobulinemia, autoantibodies detection and interface hepatitis. Due to the absence of specific diagnostic markers and the large heterogeneity of its clinical, laboratory and histological features, AIH diagnosis may be potentially difficult. Therefore, in this in-depth review we summarize the substantial progress on etiopathogenesis, clinical, serological and histological phenotypes of AIH. AIH has a global distribution affecting any age, both sexes and all ethnic groups. Clinical manifestations vary from asymptomatic to severe or rarely fulminant hepatitis. Hypergammaglobulinemia with selective elevation of IgG is found in most cases. Autoimmune attack is perpetuated, possibly via molecular mimicry, and favored by the impaired control of T-regulatory cells. Histology (interface hepatitis, emperipolesis and hepatic rosette formation) and autoantibodies detection although not pathognomonic, are still the hallmark for a timely diagnosis. AIH remains a major diagnostic challenge. AIH should be considered in every case in the absence of viral, metabolic, genetic and toxic etiology of chronic or acute hepatitis. Laboratory personnel, hepato-pathologists and clinicians need to become more familiar with disease expressions and the interpretation of liver histology and autoimmune serology to derive maximum benefit for the patient. PMID:25574080

  18. Current practice in laboratory diagnostics of autoimmune diseases in Croatia. 
Survey of the Working group for laboratory diagnostics of autoimmune diseases of the Croatian Society of Medical Biochemistry and Laboratory Medicine

    PubMed Central

    Kuna, Andrea Tešija; Đerek, Lovorka; Kozmar, Ana; Drvar, Vedrana

    2016-01-01

    Introduction With the trend of increasing incidence of autoimmune diseases, laboratories are faced with exponential growth of the requests for tests relating the diagnosis of these diseases. Unfortunately, the lack of laboratory personnel experienced in this specific discipline of laboratory diagnostic, as well as an unawareness of a method limitation often results in confusion for clinicians. The aim was to gain insight into number and type of Croatian laboratories that perform humoral diagnostics with the final goal to improve and harmonize laboratory diagnostics of autoimmune diseases in Croatia. Materials and methods In order to get insight into current laboratory practice two questionnaires, consisting of 42 questions in total, were created. Surveys were conducted using SurveyMonkey application and were sent to 88 medical biochemistry laboratories in Croatia for the first survey. Out of 33 laboratories that declared to perform diagnostic from the scope, 19 were selected for the second survey based on the tests they pleaded to perform. The survey comprised questions regarding autoantibody hallmarks of systemic autoimmune diseases while regarding organ-specific autoimmune diseases was limited to diseases of liver, gastrointestinal and nervous system. Results Response rate was high with 80 / 88 (91%) laboratories which answered the first questionnaire, and 19 / 19 (1.0) for the second questionnaire. Obtained results of surveys indicate high heterogeneity in the performance of autoantibody testing among laboratories in Croatia. Conclusions Results indicate the need of creating recommendations and algorithms in order to harmonize the approach to laboratory diagnostics of autoimmune diseases in Croatia. PMID:27812306

  19. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  20. Genetics of liver disease: From pathophysiology to clinical practice.

    PubMed

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.

  1. Molecular Mimicry as a Mechanism of Autoimmune Disease

    PubMed Central

    Cusick, Matthew F.; Libbey, Jane E.; Fujinami, Robert S.

    2012-01-01

    A variety of mechanisms have been suggested as the means by which infections can initiate and/or exacerbate autoimmune diseases. One mechanism is molecular mimicry, where a foreign antigen shares sequence or structural similarities with self-antigens. Molecular mimicry has typically been characterized on an antibody or T cell level. However, structural relatedness between pathogen and self does not account for T cell activation in a number of autoimmune diseases. A proposed mechanism that could have been misinterpreted for molecular mimicry is the expression of dual T cell receptors (TCR) on a single T cell. These T cells have dual reactivity to both foreign and self-antigens leaving the host vulnerable to foreign insults capable of triggering an autoimmune response. In this review, we briefly discuss what is known about molecular mimicry followed by a discussion of the current understanding of dual TCRs. Finally, we discuss three mechanisms, including molecular mimicry, dual TCRs and chimeric TCRs, by which dual reactivity of the T cell may play a role in autoimmune diseases. PMID:22095454

  2. Oral tolerance: mechanisms and therapy of autoimmune diseases.

    PubMed

    Koh, D R

    1998-01-01

    Oral tolerance is a state of immune hyporesponsiveness induced by the oral or mucosal exposure to antigens. This state is dependent on the dose of the oral antigen administered, with a low dose stimulating regulatory T cell development leading to an active immune suppression that is transferable via T cells. The active mechanism appears to be a cytokine mediated immune deviation with a predominant Th2 and Th3 response (TGF-beta). In contrast, high dose oral antigens lead to clonal deletion and anergy. The active suppression of low dose oral tolerance can also suppress an unrelated immune response (bystander suppression) paving the way for therapy of autoimmune diseases like rheumatoid arthritis. Oral tolerance has been effective in the treatment of autoimmune diseases like experimental autoimmune encephalomyelitis (EAE), collagen-induced arthritis (CIA) and insulin-dependent diabetes in animals. However, recent studies in human autoimmune diseases have not been as effective but the results are encouraging and more work is required to understand the mechanisms involved and other factors that may modulate the response. PMID:9588275

  3. Ultraviolet radiation and autoimmune disease: insights from epidemiological research.

    PubMed

    Ponsonby, Anne-Louise; McMichael, Anthony; van der Mei, Ingrid

    2002-12-27

    This review examines the epidemiological evidence that suggests ultraviolet radiation (UVR) may play a protective role in three autoimmune diseases: multiple sclerosis, insulin-dependent diabetes mellitus and rheumatoid arthritis. To date, most of the information has accumulated from population studies that have studied the relationship between geography or climate and autoimmune disease prevalence. An interesting gradient of increasing prevalence with increasing latitude has been observed for at least two of the three diseases. This is most evident for multiple sclerosis, but a similar gradient has been shown for insulin-dependent diabetes mellitus in Europe and North America. Seasonal influences on both disease incidence and clinical course and, more recently, analytical studies at the individual level have provided further support for a possible protective role for UVR in some of these diseases but the data are not conclusive. Organ-specific autoimmune diseases involve Th1 cell-mediated immune processes. Recent work in photoimmunology has shown ultraviolet B (UVB) can specifically attenuate these processes through several mechanisms which we discuss. In particular, the possible contribution of an UVR-induced increase in serum vitamin D (1,25(OH)2D3) levels in the beneficial immunomodulation of these diseases is discussed. PMID:12505287

  4. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    PubMed

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use. PMID:24636281

  5. [Immunomodulatory properties of stem mesenchymal cells in autoimmune diseases].

    PubMed

    Sánchez-Berná, Isabel; Santiago-Díaz, Carlos; Jiménez-Alonso, Juan

    2015-01-20

    Autoimmune diseases are a cluster of disorders characterized by a failure of the immune tolerance and a hyperactivation of the immune system that leads to a chronic inflammation state and the damage of several organs. The medications currently used to treat these diseases usually consist of immunosuppressive drugs that have significant systemic toxic effects and are associated with an increased risk of opportunistic infections. Recently, several studies have demonstrated that mesenchymal stem cells have immunomodulatory properties, a feature that make them candidates to be used in the treatment of autoimmune diseases. In the present study, we reviewed the role of this therapy in the treatment of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, Crohn's disease and multiple sclerosis, as well as the potential risks associated with its use.

  6. Obesity in autoimmune diseases: not a passive bystander.

    PubMed

    Versini, Mathilde; Jeandel, Pierre-Yves; Rosenthal, Eric; Shoenfeld, Yehuda

    2014-09-01

    In the last decades, autoimmune diseases have experienced a dramatic increase in Western countries. The involvement of environmental factors is strongly suspected to explain this rise. Particularly, over the same period, obesity has followed the same outbreak. Since the exciting discovery of the secretory properties of adipose tissue, the relationship between obesity and autoimmunity and the understanding of the underlying mechanisms have become of major interest. Indeed, the fat tissue has been found to produce a wide variety of "adipokines", involved in the regulation of numerous physiological functions, including the immune response. By conducting a systematic literature review, we extracted 329 articles regarding clinical, experimental and pathophysiological data on the relationship between obesity, adipokines - namely leptin, adiponectin, resistin, visfatin - and various immune-mediated conditions, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD), multiple sclerosis (MS), type-1 diabetes (T1D), psoriasis and psoriatic arthritis (PsA), and thyroid autoimmunity (TAI), especially Hashimoto thyroiditis (HT). The strongest levels of evidence support an increased risk of RA (OR=1.2-3.4), MS (OR=2), psoriasis and PsA (OR=1.48-6.46) in obese subjects. A higher risk of IBD, T1D and TAI is also suggested. Moreover, obesity worsens the course of RA, SLE, IBD, psoriasis and PsA, and impairs the treatment response of RA, IBD, psoriasis and PsA. Extensive clinical data and experimental models demonstrate the involvement of adipokines in the pathogenesis of these autoimmune diseases. Obesity appears to be a major environmental factor contributing to the onset and progression of autoimmune diseases. PMID:25092612

  7. EGFR Signaling in Liver Diseases

    PubMed Central

    Komposch, Karin; Sibilia, Maria

    2015-01-01

    The epidermal growth factor receptor (EGFR) is a transmembrane receptor tyrosine kinase that is activated by several ligands leading to the activation of diverse signaling pathways controlling mainly proliferation, differentiation, and survival. The EGFR signaling axis has been shown to play a key role during liver regeneration following acute and chronic liver damage, as well as in cirrhosis and hepatocellular carcinoma (HCC) highlighting the importance of the EGFR in the development of liver diseases. Despite the frequent overexpression of EGFR in human HCC, clinical studies with EGFR inhibitors have so far shown only modest results. Interestingly, a recent study has shown that in human HCC and in mouse HCC models the EGFR is upregulated in liver macrophages where it plays a tumor-promoting function. Thus, the role of EGFR in liver diseases appears to be more complex than what anticipated. Further studies are needed to improve the molecular understanding of the cell-specific signaling pathways that control disease development and progression to be able to develop better therapies targeting major components of the EGFR signaling network in selected cell types. In this review, we compiled the current knowledge of EGFR signaling in different models of liver damage and diseases, mainly derived from the analysis of HCC cell lines and genetically engineered mouse models (GEMMs). PMID:26729094

  8. Is pregnancy a risk factor for rheumatic autoimmune diseases?

    PubMed Central

    Marder, Wendy; Somers, Emily C

    2014-01-01

    Purpose of review To review the association of pregnancy with the risk of subsequent development of rheumatic autoimmune diseases in women, including rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Recent findings There is a small but growing literature related to the risk of autoimmune rheumatic disease in association with pregnancy history. However, results conflict both in terms of the direction and magnitude of risk of disease in relationship to prior pregnancy history. Although anecdotal evidence tends to favor the premise that pregnancy is protective against certain diseases, such as rheumatoid arthritis, the heterogeneity of results precludes the ability to confirm an association in either direction. There is indication that time elapsed since pregnancy may influence risk, with the postpartum year being of particular relevance. Summary To date, a clear pattern has not emerged regarding pregnancy and the future risk of autoimmune rheumatic diseases. This topic requires greater study, and given the strong female preponderance of these diseases, future research efforts should seek to resolve this important issue. PMID:24646947

  9. Liver diseases in pregnancy: Diseases not unique to pregnancy

    PubMed Central

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-01-01

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson’s disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy. PMID:24282352

  10. Liver diseases in pregnancy: diseases not unique to pregnancy.

    PubMed

    Almashhrawi, Ashraf A; Ahmed, Khulood T; Rahman, Rubayat N; Hammoud, Ghassan M; Ibdah, Jamal A

    2013-11-21

    Pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver. Liver disease can cause significant morbidity and mortality in both pregnant women and their infants. Few challenges arise in reaching an accurate diagnosis in light of such physiological changes. Laboratory test results should be carefully interpreted and the knowledge of what normal changes to expect is prudent to avoid clinical misjudgment. Other challenges entail the methods of treatment and their safety for both the mother and the baby. This review summarizes liver diseases that are not unique to pregnancy. We focus on viral hepatitis and its mode of transmission, diagnosis, effect on the pregnancy, the mother, the infant, treatment, and breast-feeding. Autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, Wilson's disease, Budd Chiari and portal vein thrombosis in pregnancy are also discussed. Pregnancy is rare in patients with cirrhosis because of the metabolic and hormonal changes associated with cirrhosis. Variceal bleeding can happen in up to 38% of cirrhotic pregnant women. Management of portal hypertension during pregnancy is discussed. Pregnancy increases the pathogenicity leading to an increase in the rate of gallstones. We discuss some of the interventions for gallstones in pregnancy if symptoms arise. Finally, we provide an overview of some of the options in managing hepatic adenomas and hepatocellular carcinoma during pregnancy.

  11. Liver disease in vineyard sprayers.

    PubMed

    Pimentel, J C; Menezes, A P

    1977-02-01

    Liver disease with inclusions of copper was recognized among 30 rural workers with "vineyard sprayer's lung." The pathological findings were varied: focal or diffuse swelling and proliferation of Kupffer cells; histiocytic and sarcoid-like granulomata; fibrosis of variable degree in the perisinusoidal, portal, and subcapsular areas, accompanied by atypical proliferation of the sinusoidal lining cells; micronodular cirrhosis; angiosarcoma of the liver; idiopathic portal hypertension. Abundant deposits of copper were revealed by histochemical techniques within hepatic and pulmonary lesions in these patients. The observations on the human and experimental material suggest an etiological relationship between exposure to copper sulfate and the lesions described. A morphological resemblance was noted between the "liver disease of vineyard sprayers" and the hepatic lesions reported in workers exposed to inorganic arsenic and to vinyl chloride. The identification of the inhaled foreign material within the liver lesions raises important etiological considerations.

  12. Folate, alcohol, and liver disease.

    PubMed

    Medici, Valentina; Halsted, Charles H

    2013-04-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

  13. Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

    PubMed

    Ramos-Leví, Ana Maria; Marazuela, Mónica

    2016-10-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs).

  14. Siglec-1 and -2 as potential biomarkers in autoimmune disease.

    PubMed

    Eakin, Amanda J; Bustard, Michael J; McGeough, Cathy M; Ahmed, Tahanver; Bjourson, Anthony J; Gibson, David S

    2016-06-01

    Autoimmune diseases (ADs) are currently treated with anti-inflammatory and immunosuppressive drugs, aimed at reducing symptoms of disease in order to improve quality of life for patients. However, for a significant number of patients these therapies are ineffective, leading to an increased risk of irreversible damage and eventual disability in certain cases. Growing evidence has implicated glycosylated proteins and their cognate receptors in modulation of the autoimmune response. This review will summarize these findings with particular focus on sialic acid-binding immunoglobulin-like lectin (Siglec)-1 and Siglec-2 involvement in AD. Fluctuations in these glycosylation-dependent pathways could act as sentinels of disease activity or drug responses. If validated, protein modification and cellular response markers could help clinicians achieve remission earlier. PMID:26752092

  15. Siglec-1 and -2 as potential biomarkers in autoimmune disease.

    PubMed

    Eakin, Amanda J; Bustard, Michael J; McGeough, Cathy M; Ahmed, Tahanver; Bjourson, Anthony J; Gibson, David S

    2016-06-01

    Autoimmune diseases (ADs) are currently treated with anti-inflammatory and immunosuppressive drugs, aimed at reducing symptoms of disease in order to improve quality of life for patients. However, for a significant number of patients these therapies are ineffective, leading to an increased risk of irreversible damage and eventual disability in certain cases. Growing evidence has implicated glycosylated proteins and their cognate receptors in modulation of the autoimmune response. This review will summarize these findings with particular focus on sialic acid-binding immunoglobulin-like lectin (Siglec)-1 and Siglec-2 involvement in AD. Fluctuations in these glycosylation-dependent pathways could act as sentinels of disease activity or drug responses. If validated, protein modification and cellular response markers could help clinicians achieve remission earlier.

  16. The pleiotropic role of HDL in autoimmune diseases.

    PubMed

    Parra, Sandra; Castro, Antoni; Masana, Luis

    2015-01-01

    As is widely known, the classic function of HDL is reverse cholesterol transport (RCT), thus removing cholesterol from peripheral tissues. Early epidemiological studies, such as Framingham's, stated that increased HDL levels were associated with a significant decrease in relative risk for cardiovascular disease (CVD) mortality. However, those with heightened expectations in recent years for the development of therapeutic targets to increase HDL levels have been disappointed, because efforts have demonstrated the opposite effect on cardiovascular and global mortality. However, in contrast, studies have highlighted the complexity and the intriguing role of HDL in different pathological conditions, such as infections, neoplasms, and autoimmune diseases. In this review an attempt is made to summarize some biological pathways that link HDL function with the immune system, and its possible clinical repercussions in autoimmune diseases.

  17. How do autoimmune diseases cluster in families? A systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Background A primary characteristic of complex genetic diseases is that affected individuals tend to cluster in families (that is, familial aggregation). Aggregation of the same autoimmune condition, also referred to as familial autoimmune disease, has been extensively evaluated. However, aggregation of diverse autoimmune diseases, also known as familial autoimmunity, has been overlooked. Therefore, a systematic review and meta-analysis were performed aimed at gathering evidence about this topic. Methods Familial autoimmunity was investigated in five major autoimmune diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, autoimmune thyroid disease, multiple sclerosis and type 1 diabetes mellitus. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed. Articles were searched in Pubmed and Embase databases. Results Out of a total of 61 articles, 44 were selected for final analysis. Familial autoimmunity was found in all the autoimmune diseases investigated. Aggregation of autoimmune thyroid disease, followed by systemic lupus erythematosus and rheumatoid arthritis, was the most encountered. Conclusions Familial autoimmunity is a frequently seen condition. Further study of familial autoimmunity will help to decipher the common mechanisms of autoimmunity. PMID:23497011

  18. [Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

    PubMed

    Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2016-10-01

    Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential. PMID:27143525

  19. [Pregnancy in systemic autoimmune diseases: Myths, certainties and doubts].

    PubMed

    Danza, Álvaro; Ruiz-Irastorza, Guillermo; Khamashta, Munther

    2016-10-01

    Systemic autoimmune diseases especially affect young women during childbearing age. The aim of this review is to update systemic lupus erythematosus, antiphospholipid syndrome and systemic sclerosis management during pregnancy. These diseases present variable maternal and fetal risks. Studies show that an appropriate disease control and a reasonable remission period prior to pregnancy are associated with satisfactory obstetric outcomes. Antiphospholipid autoantibodies profile, anti-Ro/anti-La antibodies, pulmonary pressure and activity evaluation are crucial to assess the pregnancy risk. Monitoring requires a multidisciplinary team, serial analytic controls and Doppler ultrasound of maternal and fetal circulation. Evaluation of the activity of the disease is essential.

  20. Liver Disease and IBD

    MedlinePlus

    ... 34% of Crohn’s patients with disease of the terminal ileum (the last segment of the small intestine). ... increased risk for developing gallstones because the diseased terminal ileum cannot absorb bile salts, which are necessary ...

  1. Non-Alcoholic Fatty Liver Disease (NAFLD)

    MedlinePlus

    Non-Alcoholic Fatty Liver Disease What is Non-alcoholic fatty liver disease (NAFLD)? FAT N AFLD is a name that is given to a ... and under “Liver Health Information view ‘Nonalcoholic fatty liver Disease (NAFLD/NASH)’ IMPORTANT REMINDER: This information from the ...

  2. [Endogenous retroviruses are associated with autoimmune diseases].

    PubMed

    Nexø, Bjørn A; Jensen, Sara B; Hansen, Bettina; Laska, Magdalena J

    2016-06-13

    Retroviruses can be transmitted in two fundamentally different ways: 1) They can be horizontally transmitted as infectious virus, or 2) they can integrate in the germ line and be transmitted to offspring and the offsprings' offspring as DNA. The latter is called endogenous viruses. The mode of transmission is called vertical. Viral variants of importance for development of disease must be more frequent among diseased persons than among healthy individuals. Multiple sclerosis, diabetes and rheumatoid arthritis are all associated with sets of endogenouos retroviruses but not the same sets. If a virus grows and this contributes to disease, one should be able to alleviate disease with antiretroviral drugs. We call for clinical trials to elucidate this issue. PMID:27292833

  3. IL-10 Modulates Th17 Pathogenicity during Autoimmune Diseases

    PubMed Central

    Guo, Beichu

    2016-01-01

    The immune system is essential for host defense against pathogen infections; however dysregulated immune response may lead to inflammatory or autoimmune diseases. Elevated activation of both innate immune cells and T cells such as Th17 cells are linked to many autoimmune diseases, including Multiple Sclerosis (MS), arthritis and inflammatory bowel disease (IBD). To keep immune homeostasis, the immune system develops a number of negative feedback mechanisms, such as the production of anti-inflammatory cytokine IL-10, to dampen excessive production of inflammatory cytokines and uncontrolled activation of immune cells. Our recent studies uncover a novel immunoregulatory function of interferon (IFN) pathways on the innate and antigen-specific immune response. Our results show that IFNα/β induced IL-10 production from macrophages and Th17 cells, which in turn negatively regulated Th17 function in autoimmune diseases such as Experimental Allergic Encephalomyelitis (EAE), an animal model of human MS. In a chronic colitis model resembling human IBD, we also found that IL-10 inhibited inflammasome/IL-1 pathway, and the pathogenicity of Th17 cells, leading to reduced chronic intestinal inflammation. Results from our and other studies further suggest that IL-10 produced by both macrophages and regulatory T cells may shift Th17 into more regulatory phenotypes, leading to reduced inflammatory response. PMID:27308096

  4. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system’s search for antibodies, a balance has evolved between binding affinity and specificity.

  5. Phenomics in Autoimmune and Inflammatory Diseases

    ClinicalTrials.gov

    2016-04-18

    Healthy Volunteer; Rheumatoid Arthritis; Ankylosing Spondylitis; Systemic Lupus Erythematosus/Antiphospholipid Syndrome; FMF; Cryopyrin-Associated Periodic Syndromes /TNF-receptor Associated Periodic Syndrome; Vasculitis; Uveitis; Myositis; Crohn's Disease; Ulcerative Rectocolitis; Type 1 Diabetes; Unclassified IAD Knee and/or Hip Arthritis, Muscular Dystrophy

  6. Undifferentiated vasculitis or an evolving systemic autoimmune rheumatic disease?

    PubMed

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-08-01

    Undifferentiated connective tissue diseases usually present with arthralgias, sicca symptoms, Raynaud's phenomenon and leucopenia. This case presents the atypical presentation of an undifferentiated connective tissue disease with extensive cutaneous involvement of fingers and toes leading to gangrene with absence of typical rheumatological symptoms. The autoimmune profile showed positive ANA and anti-Ro/SS-A. Thromboembolism was ruled out on the basis of transthoracic and transesophageal echo. She was treated with I/V corticosteroids and cyclophosphamide that halted the disease progression. PMID:27574560

  7. Undifferentiated vasculitis or an evolving systemic autoimmune rheumatic disease?

    PubMed Central

    Fatimah, Nafeesah; Ussaid, Ahmad; Rasheed, Aflak

    2016-01-01

    Undifferentiated connective tissue diseases usually present with arthralgias, sicca symptoms, Raynaud's phenomenon and leucopenia. This case presents the atypical presentation of an undifferentiated connective tissue disease with extensive cutaneous involvement of fingers and toes leading to gangrene with absence of typical rheumatological symptoms. The autoimmune profile showed positive ANA and anti-Ro/SS-A. Thromboembolism was ruled out on the basis of transthoracic and transesophageal echo. She was treated with I/V corticosteroids and cyclophosphamide that halted the disease progression. PMID:27574560

  8. Socioeconomic status. The relationship with health and autoimmune diseases.

    PubMed

    Calixto, Omar-Javier; Anaya, Juan-Manuel

    2014-06-01

    Socioeconomic status (SES) is a hierarchical social classification associated with different outcomes in health and disease. The most important factors influencing SES are income, educational level, occupational class, social class, and ancestry. These factors are closely related to each other as they present certain dependent interactions. Since there is a need to improve the understanding of the concept of SES and the ways it affects health and disease, we review herein the tools currently available to evaluate SES and its relationship with health and autoimmune diseases. PMID:24418307

  9. Socioeconomic status. The relationship with health and autoimmune diseases.

    PubMed

    Calixto, Omar-Javier; Anaya, Juan-Manuel

    2014-06-01

    Socioeconomic status (SES) is a hierarchical social classification associated with different outcomes in health and disease. The most important factors influencing SES are income, educational level, occupational class, social class, and ancestry. These factors are closely related to each other as they present certain dependent interactions. Since there is a need to improve the understanding of the concept of SES and the ways it affects health and disease, we review herein the tools currently available to evaluate SES and its relationship with health and autoimmune diseases.

  10. Biologic therapy for autoimmune diseases: an update.

    PubMed

    Rosman, Ziv; Shoenfeld, Yehuda; Zandman-Goddard, Gisele

    2013-01-01

    Biologic therapies for rheumatologic diseases, which are targeted at molecules involved in the mechanisms of the immune system, provide an alternative to the existing treatment methods of disease-modifying anti-rheumatic drugs and other immunosuppressive medications. However, the current drawbacks of biologic therapies, including the inconvenience of intravenous administration, the high costs of these drugs, and the adverse events associated with them, prevent their wide use as first-line medications. This review provides an update of the recent literature on the new biologic therapies available. The review concentrates on nine drugs: tocilizumab, rituximab, ofatumumab, belimumab, epratuzumab, abatacept, golimumab, certolizumab, and sifalimumab, which are used as therapies for rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, or vasculitis. PMID:23557513

  11. Novel therapies for memory cells in autoimmune diseases.

    PubMed

    Bhargava, P; Calabresi, P A

    2015-06-01

    Autoimmune diseases are a major cause of morbidity, and their incidence and prevalence continue to rise. Treatments for these diseases are non-specific and result in significant adverse effects. Targeted therapies may help in improving the risk : benefit ratio associated with treatment. Immunological memory is an important feature of the vertebrate immune system that results in the production of cells that are long-lived and able to respond to antigens in a more robust manner. In the setting of autoimmunity this characteristic becomes detrimental due to the ongoing response to a self-antigen(s). These memory cells have been shown to play key roles in various autoimmune diseases such as type 1 diabetes, multiple sclerosis and psoriasis. Memory T cells and B cells can be identified based on various molecules expressed on their surface. Memory T cells can be divided into three main categories - central memory, effector memory and resident memory cells. These subsets have different proliferative potential and cytokine-producing abilities. Utilizing differentially expressed surface molecules or downstream signalling pathway proteins in these cells it is now possible to target memory cells while sparing naive cells. We will discuss the various available options for such a strategy and several potential strategies that may yield successful therapies in the future.

  12. Scavenging nucleic acid debris to combat autoimmunity and infectious disease

    NASA Astrophysics Data System (ADS)

    Holl, Eda K.; Shumansky, Kara L.; Borst, Luke B.; Burnette, Angela D.; Sample, Christopher J.; Ramsburg, Elizabeth A.; Sullenger, Bruce A.

    2016-08-01

    Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.

  13. Cancer among children of parents with autoimmune diseases

    PubMed Central

    Mellemkjær, L; Alexander, F; Olsen, J H

    2000-01-01

    Many different aetiologies for childhood cancer have been suggested, but few are well established. One is that parental autoimmune disease is linked with susceptibility for haematopoietic malignancies in their offspring during childhood. The present study is the first to investigate this hypothesis using a follow-up design. A cohort of 53 811 children of more than 36 000 patients diagnosed with a systemic, organ-specific or suspected autoimmune disease were followed up for cancer incidence in the Danish Cancer Registry during 1968–1993. The parents were identified through the National Registry of Patients, while their children were traced in the Central Population Register. Cancer incidence among the offspring was compared with that in the corresponding childhood population of Denmark. In total, 115 cancers were observed among children aged 0–19 years, yielding a non-significant standardized incidence ratio of 1.07. Lymphomas contributed 21 cases to the overall number of tumours, 60% more than expected (95% confidence interval (CI) 1.0–2.4); leukaemia contributed 37 cases representing an excess of 30% (95% CI 0.9–1.8). Our results give some support to the hypothesis that parental autoimmune disease is associated with childhood lymphoma and leukaemia. © 2000 Cancer Research Campaign PMID:10755414

  14. Scavenging nucleic acid debris to combat autoimmunity and infectious disease.

    PubMed

    Holl, Eda K; Shumansky, Kara L; Borst, Luke B; Burnette, Angela D; Sample, Christopher J; Ramsburg, Elizabeth A; Sullenger, Bruce A

    2016-08-30

    Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal's ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases. PMID:27528673

  15. [Narcolepsy with cataplexy: an autoimmune disease?].

    PubMed

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix. PMID:25537044

  16. [Narcolepsy with cataplexy: an autoimmune disease?].

    PubMed

    Jacob, Louis; Dauvilliers, Yves

    2014-12-01

    Narcolepsy type 1 (also named narcolepsy-cataplexy or hypocretin deficiency syndrome) is a rare sleep disorder characterized by excessive daytime sleepiness and cataplexy, plus frequently hypnagogic hallucinations, sleep paralysis and nocturnal sleep disturbances. Narcolepsy type 1 is an immune system-associated disease linked with the destruction of 70.000-90.000 hypocretin neurons notably involved in wakefulness. Among narcoleptic patients, 98% are positive for HLA-DQB1*06:02, a HLA class II allele, against 20-25% in general population. Individuals carrying HLA-DQB1*06:02 have an extraordinary risk to develop narcolepsy (odd ratio: 251). Other genes involved in CD4+ T cells and immune system activation as T-cell receptor α are also associated with narcolepsy. The development of the disease is linked with environmental factors such as influenza and streptococcal infections. Narcolepsy type 1 incidence also increased in Europe following the use of Pandemrix, a 2009 H1N1 AS03-adjuvanted vaccine manufactured by GlaxoSmithKline. Interestingly, such increase was not observed with Arepanrix, another vaccine developed by GSK very similar to Pandemrix.

  17. Liver transplantation for Wilson disease

    PubMed Central

    Catana, Andreea M; Medici, Valentina

    2012-01-01

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  18. Liver transplantation for Wilson disease.

    PubMed

    Catana, Andreea M; Medici, Valentina

    2012-01-27

    The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

  19. Pharmacotherapy of cholestatic liver diseases.

    PubMed

    Paumgartner, Gustav

    2010-06-01

    New insights into the molecular mechanisms of bile formation and cholestasis have provided new concepts for pharmacotherapy of cholestatic liver diseases. The major aim in all forms of cholestasis is the reduction of hepatocellular retention of bile acids and other potentially toxic constituents of bile. Reduction of hepatocellular retention may be achieved by drugs that stimulate hepatocellular secretion via the canalicular route into the bile or via the alternative route across the basolateral membrane into the blood, and by drugs that stimulate the hepatocellular metabolism of hydrophobic bile acids to hydrophilic, less toxic metabolites. In cholestatic liver diseases that start with an injury of the biliary epithelium (e.g., primary biliary cirrhosis; PBC), protection of the cholangiocytes against the toxic effects of hydrophobic bile acids is most important. When hepatocellular retention of bile acids has occurred, the inhibition of bile acid-induced apoptosis becomes another target of therapy. Ursodeoxycholic acid protects the biliary epithelium by reducing the toxicity of bile, stimulates hepatobiliary secretion by upregulating transporters and inhibits apoptosis. It is the mainstay of therapy in PBC but of benefit also in a number of other cholestatic liver diseases. New drugs such as 6-ethyl-chenodeoxycholic acid and 24-nor-ursodeoxycholic acid are being evaluated for the treatment of cholestatic liver diseases.

  20. Cholestatic liver disease masquerading as Wilson disease.

    PubMed

    Sood, Vikrant; Rawat, Dinesh; Khanna, Rajeev; Alam, Seema

    2015-03-01

    Wilson disease and cholestatic liver diseases may present as a diagnostic dilemma if standard guidelines incorporating markers of copper overload are followed. We hereby present a series of four cases of sclerosing cholangitis masquerading as Wilson disease. True Wilson disease cases had significantly lower ceruloplasmin (6 vs. 16 mg/dL) and higher 24-hour urinary copper (322.3 vs. 74.5 μg/day) as compared to mimickers. Initial low serum ceruloplasmin levels normalized in mimickers on follow up, and this may used as a diagnostic indicator. Standard Wilson disease diagnostic criteria thus need further modification especially in developing countries to help avoid mismanagement.

  1. Subsequent Type 2 Diabetes in Patients with Autoimmune Disease.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Sundquist, Jan; Sundquist, Kristina; Ji, Jianguang

    2015-01-01

    Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incidence ratios (SIRs) were calculated for T2D diagnosis in patients with previously diagnosed AId and compared to those without a previous AId. Among a total of 757,368 AId patients, 15,103 were diagnosed with T2D, giving an overall SIR for T2D of 1.66. T2D risks were increased after 27 AIds; the highest SIRs were noted for chorea minor (8.00), lupoid hepatitis (5.75), and Addison disease (2.63). T2D was increased after 27 of 32 AIds but we were unable to control for factors such as obesity and smoking. However, the clearly increased risks for T2D in most types of AId patients, and in reverse order increased risks for AId after T2D, do not support an overall confounding by life-style factors. Mechanistic links shared by T2D, AId and life-style factors such as obesity, perhaps through chronic inflammation, may drive autoimmune activation of T2D and many AIds. PMID:26350756

  2. The PD-1/PD-Ls pathway and autoimmune diseases.

    PubMed

    Dai, Suya; Jia, Ru; Zhang, Xiao; Fang, Qiwen; Huang, Lijuan

    2014-07-01

    The programmed death (PD)-1/PD-1 ligands (PD-Ls) pathway, is a new member of the B7/CD28 family, and consists of the PD-1 receptor and its ligands PD-L1 (B7-H1, CD274) and PD-L2 (B7-DC, CD273). Recently, it is reported that PD-1, PD-L1 and PD-L2 also have soluble forms aside from their membrane bound forms. The soluble forms increase the diversity and complexity of PD-1/PD-Ls pathway in both composition and function. The PD-1/PD-Ls pathway is broadly expressed and exerts a wider range of immunoregulatory roles in T-cell activation and tolerance compared with other B7/CD28 family members. Studies show that the PD-1/PD-Ls pathway regulates the induction and maintenance of peripheral tolerance and protects tissues from autoimmune attack in physiological conditions. In addition, it is also involved in various diseases mediated by T cells, such as autoimmunity, tumor immunity, chronic viral infections, and transplantation immunity. In this review, we will summarize the relevance of the soluble forms and the latest researches on the role of PD-1/PD-Ls pathway in autoimmune diseases.

  3. The immunobiology of Campylobacter jejuni: Innate immunity and autoimmune diseases.

    PubMed

    Phongsisay, Vongsavanh

    2016-04-01

    The Gram-negative bacterium Campylobacter jejuni causes gastroenteritis and Guillain-Barré syndrome in humans. Recent advances in the immunobiology of C. jejuni have been made. This review summarizes C. jejuni-binding innate receptors and highlights the role of innate immunity in autoimmune diseases. This human pathogen produces a variety of glycoconjugates, including human ganglioside-like determinants and multiple activators of Toll-like receptors (TLRs). Furthermore, C. jejuni targets MyD88, NLRP3 inflammasome, TIR-domain-containing adapter-inducing interferon-β (TRIF), sialic acid-binding immunoglobulin-like lectins (Siglecs), macrophage galactose-type lectin (MGL), and immunoglobulin-like receptors (TREM2, LMIR5/CD300b). The roles of these innate receptors and signaling molecules have been extensively studied. MyD88-mediated TLR activation or inflammasome-dependent IL-1β secretion is essential for autoimmune induction. TRIF mediates the production of type I interferons that promote humoral immune responses and immunoglobulin class-switching. Siglec-1 and Siglec-7 interact directly with gangliosides. Siglec-1 activation enhances phagocytosis and inflammatory responses. MGL internalizes GalNAc-containing glycoconjugates. TREM2 is well-known for its role in phagocytosis. LMIR5 recognizes C. jejuni components and endogenous sulfoglycolipids. Several lines of evidence from animal models of autoimmune diseases suggest that simultaneous activation of innate immunity in the presence of autoreactive lymphocytes or antigen mimicry may link C. jejuni to immunopathology.

  4. Subsequent Type 2 Diabetes in Patients with Autoimmune Disease

    PubMed Central

    Hemminki, Kari; Liu, Xiangdong; Försti, Asta; Sundquist, Jan; Sundquist, Kristina; Ji, Jianguang

    2015-01-01

    Immunological data show that type 2 diabetes (T2D) manifests autoimmune features. We wanted to test the association epidemiologically by assessing subsequent diagnosis of T2D following diagnosis of autoimmune disease (AId) and subsequent AId after T2D in the same individuals. Patients were identified from three Swedish health databases. A total of 32 different AId were included. Standardized incidence ratios (SIRs) were calculated for T2D diagnosis in patients with previously diagnosed AId and compared to those without a previous AId. Among a total of 757,368 AId patients, 15,103 were diagnosed with T2D, giving an overall SIR for T2D of 1.66. T2D risks were increased after 27 AIds; the highest SIRs were noted for chorea minor (8.00), lupoid hepatitis (5.75), and Addison disease (2.63). T2D was increased after 27 of 32 AIds but we were unable to control for factors such as obesity and smoking. However, the clearly increased risks for T2D in most types of AId patients, and in reverse order increased risks for AId after T2D, do not support an overall confounding by life-style factors. Mechanistic links shared by T2D, AId and life-style factors such as obesity, perhaps through chronic inflammation, may drive autoimmune activation of T2D and many AIds. PMID:26350756

  5. Immune mechanisms in alcoholic liver disease

    PubMed Central

    Vidali, Matteo

    2009-01-01

    Growing evidence indicates that inflammatory reactions play an important role in the pathogenesis of alcoholic liver disease (ALD). The implication of immunity in fueling chronic inflammation in ALD has emerged from clinical and experimental evidence showing the recruitment and the activation of lymphocytes in the inflammatory infiltrates of ALD and has received further support by the recent demonstration of a role of Th17 lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immune responses are still incompletely characterized. Patients with advanced ALD show a high prevalence of circulating IgG and T-lymphocytes towards epitopes derived from protein modification by hydroxyethyl free radicals (HER) and end-products of lipid peroxidation. In both chronic alcohol-fed rats and heavy drinkers the elevation of IgG against lipid peroxidation-derived antigens is associated with an increased production of pro-inflammatory cytokines/chemokines and with the severity of histological signs of liver inflammation. Moreover, CYP2E1-alkylation by HER favors the development of anti-CYP2E1 auto-antibodies in a sub-set of ALD patients. Altogether, these results suggest that allo- and auto-immune reactions triggered by oxidative stress might contribute to fuel chronic hepatic inflammation during the progression of ALD. PMID:19809845

  6. Multisensory body representation in autoimmune diseases.

    PubMed

    Finotti, Gianluca; Costantini, Marcello

    2016-02-12

    Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system's functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist.

  7. Multisensory body representation in autoimmune diseases

    PubMed Central

    Finotti, Gianluca; Costantini, Marcello

    2016-01-01

    Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system’s functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist. PMID:26867786

  8. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    PubMed Central

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  9. Teen Obesity May Mean Liver Disease Later

    MedlinePlus

    ... news/fullstory_159416.html Teen Obesity May Mean Liver Disease Later Study found risk increased as weight went ... obese could be at increased risk for severe liver disease later in life, a new study suggests. The ...

  10. Gut microbiota and liver disease.

    PubMed

    Goel, Amit; Gupta, Mahesh; Aggarwal, Rakesh

    2014-06-01

    Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non-alcoholic fatty liver disease (including obesity), non-alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.

  11. [Liver ultrasound: focal lesions and diffuse diseases].

    PubMed

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed.

  12. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases. PMID:22922229

  13. Seven newly identified loci for autoimmune thyroid disease.

    PubMed

    Cooper, Jason D; Simmonds, Matthew J; Walker, Neil M; Burren, Oliver; Brand, Oliver J; Guo, Hui; Wallace, Chris; Stevens, Helen; Coleman, Gillian; Franklyn, Jayne A; Todd, John A; Gough, Stephen C L

    2012-12-01

    Autoimmune thyroid disease (AITD), including Graves' disease (GD) and Hashimoto's thyroiditis (HT), is one of the most common of the immune-mediated diseases. To further investigate the genetic determinants of AITD, we conducted an association study using a custom-made single-nucleotide polymorphism (SNP) array, the ImmunoChip. The SNP array contains all known and genotype-able SNPs across 186 distinct susceptibility loci associated with one or more immune-mediated diseases. After stringent quality control, we analysed 103 875 common SNPs (minor allele frequency >0.05) in 2285 GD and 462 HT patients and 9364 controls. We found evidence for seven new AITD risk loci (P < 1.12 × 10(-6); a permutation test derived significance threshold), five at locations previously associated and two at locations awaiting confirmation, with other immune-mediated diseases.

  14. Diagnosis of alcoholic liver disease.

    PubMed

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-09-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  15. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  16. Sclerostin serum levels in patients with systemic autoimmune diseases.

    PubMed

    Fernández-Roldán, Concepción; Genre, Fernanda; López-Mejías, Raquel; Ubilla, Begoña; Mijares, Verónica; Cano, Daniel Sánchez; Robles, Concepción López; Callejas-Rubio, José Luis; Fernández, Raquel Ríos; Ruiz, Manuela Expósito; González-Gay, Miguel Á; Ortego Centeno, Norberto

    2016-01-01

    Systemic autoimmune diseases (SADs) are associated with lower bone mass and an increased risk of fractures. Sclerostin has a pivotal role in bone metabolism. Available data on circulating sclerostin levels in healthy subjects are limited, whereas those in SAD patients are absent. Our objective was to determine circulating sclerostin concentrations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Crohn's disease (CD) patients, and to analyze the factors associated with sclerostin concentrations. In this cross-sectional case-control study, serum sclerostin levels were measured in 38 SLE patients, 20 CD patients, 8 SSc patients and 20 healthy controls using a sclerostin ELISA. The mean values of the sclerostin (95% confidence interval) were 35.36 pmol l(-1) (12-101) in patients and 33.92 pmol l(-1) (2.31-100) in control subjects. The mean sclerostin value was 36.4 pmol l(-1) (22.1-48.5) in SLE patients, 26.7 pmol l(-1) (17.3-36.3) in CD patients and 51.8 pmol l(-1) (26.5-77.1) in SSc patients (P=0.001). Serum sclerostin levels were positively correlated with age (P<0.001), body mass index (BMI) (P=0.01) and lumbar spine Z-score (P=0.001) and negatively with creatinine clearance (P=0.001). Glucocorticoid treatment did not affect sclerostin levels. Sclerostin levels seem to have a heterogeneous pattern in different autoimmune diseases. SLE and SSc patients did not differ from healthy controls regarding sclerostin levels. The CD group had significantly lower values compared with SSc patients. Factors associated with sclerostin levels in autoimmune diseases seem to be the same than in the general population. PMID:26909149

  17. Is there a Common Genetic Basis for Autoimmune Diseases?

    PubMed Central

    Anaya, Juan-Manuel; Gómez, LuisMiguel; Castiblanco, John

    2006-01-01

    Autoimmune diseases (ADs) represent a diverse collection of diseases in terms of their demographic profile and primary clinical manifestations. The commonality between them however, is the damage to tissues and organs that arises from the response to self-antigens. The presence of shared pathophysiological mechanisms within ADs has stimulated searches for common genetic roots to these diseases. Two approaches have been undertaken to sustain the “common genetic origin” theory of ADs. Firstly, a clinical genetic analysis showed that autoimmunity aggregates within families of probands diagnosed with primary Sjögren's (pSS) syndrome or type 1 diabetes mellitus (T1D). A literature review supported the establishment of a familiar cluster of ADs depending upon the proband's disease phenotype. Secondly, in a same and well-defined population, a large genetic association study indicated that a number of polymorphic genes (i.e. HLA-DRB1, TNF and PTPN22) influence the susceptibility for acquiring different ADs. Likewise, association and linkage studies in different populations have revealed that several susceptibility loci overlap in ADs, and clinical studies have shown that frequent clustering of several ADs occurs. Thus, the genetic factors for ADs consist of two types: those which are common to many ADs (acting in epistatic pleitropy) and those that are specific to a given disorder. Their identification and functional characterization will allow us to predict their effect as well as to indicate potential new therapeutic interventions. Both autoimmunity family history and the co-occurrence of ADs in affected probands should be considered when performing genetic association and linkage studies. PMID:17162361

  18. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.

    PubMed

    Alvaro-Benito, Miguel; Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-08-01

    Classical MHC class II (MHCII) proteins present peptides for CD4(+) T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level.

  19. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases.

    PubMed

    Alvaro-Benito, Miguel; Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-08-01

    Classical MHC class II (MHCII) proteins present peptides for CD4(+) T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level. PMID:27534821

  20. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases

    PubMed Central

    Morrison, Eliot; Wieczorek, Marek; Sticht, Jana; Freund, Christian

    2016-01-01

    Classical MHC class II (MHCII) proteins present peptides for CD4+ T-cell surveillance and are by far the most prominent risk factor for a number of autoimmune disorders. To date, many studies have shown that this link between particular MHCII alleles and disease depends on the MHCII's particular ability to bind and present certain peptides in specific physiological contexts. However, less attention has been paid to the non-classical MHCII molecule human leucocyte antigen-DM, which catalyses peptide exchange on classical MHCII proteins acting as a peptide editor. DM function impacts the presentation of both antigenic peptides in the periphery and key self-peptides during T-cell development in the thymus. In this way, DM activity directly influences the response to pathogens, as well as mechanisms of self-tolerance acquisition. While decreased DM editing of particular MHCII proteins has been proposed to be related to autoimmune disorders, no experimental evidence for different DM catalytic properties had been reported until recently. Biochemical and structural investigations, together with new animal models of loss of DM activity, have provided an attractive foundation for identifying different catalytic efficiencies for DM allotypes. Here, we revisit the current knowledge of DM function and discuss how DM function may impart autoimmunity at the organism level. PMID:27534821

  1. Origin of B-Cell Neoplasms in Autoimmune Disease

    PubMed Central

    Hemminki, Kari; Liu, Xiangdong; Ji, Jianguang; Försti, Asta

    2016-01-01

    Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. PMID:27355450

  2. Origin of B-Cell Neoplasms in Autoimmune Disease.

    PubMed

    Hemminki, Kari; Liu, Xiangdong; Ji, Jianguang; Försti, Asta

    2016-01-01

    Autoimmune diseases (ADs) are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC)-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis). By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation. PMID:27355450

  3. Osteoporosis in liver disease: pathogenesis and management

    PubMed Central

    Handzlik-Orlik, Gabriela; Holecki, Michał; Wilczyński, Krzysztof; Duława, Jan

    2016-01-01

    Osteoporosis affects a substantial proportion of patients with chronic liver disease. Pathologic fracture in osteoporosis significantly affects quality of life and life expectancy. By some estimates, 40% of patients with chronic liver disease may experience osteoporotic fracture. In this study we review the pathogenesis, diagnosis and treatment of specific liver disease entities and their relation to osteoporosis. PMID:27293541

  4. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and

  5. Kidneys in chronic liver diseases

    PubMed Central

    Hartleb, Marek; Gutkowski, Krzysztof

    2012-01-01

    Acute kidney injury (AKI), defined as an abrupt increase in the serum creatinine level by at least 0.3 mg/dL, occurs in about 20% of patients hospitalized for decompensating liver cirrhosis. Patients with cirrhosis are susceptible to developing AKI because of the progressive vasodilatory state, reduced effective blood volume and stimulation of vasoconstrictor hormones. The most common causes of AKI in cirrhosis are pre-renal azotemia, hepatorenal syndrome and acute tubular necrosis. Differential diagnosis is based on analysis of circumstances of AKI development, natriuresis, urine osmolality, response to withdrawal of diuretics and volume repletion, and rarely on renal biopsy. Chronic glomerulonephritis and obstructive uropathy are rare causes of azotemia in cirrhotic patients. AKI is one of the last events in the natural history of chronic liver disease, therefore, such patients should have an expedited referral for liver transplantation. Hepatorenal syndrome (HRS) is initiated by progressive portal hypertension, and may be prematurely triggered by bacterial infections, nonbacterial systemic inflammatory reactions, excessive diuresis, gastrointestinal hemorrhage, diarrhea or nephrotoxic agents. Each type of renal disease has a specific treatment approach ranging from repletion of the vascular system to renal replacement therapy. The treatment of choice in type 1 hepatorenal syndrome is a combination of vasoconstrictor with albumin infusion, which is effective in about 50% of patients. The second-line treatment of HRS involves a transjugular intrahepatic portosystemic shunt, renal vasoprotection or systems of artificial liver support. PMID:22791939

  6. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  7. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases.

    PubMed

    Ha, Tai-You

    2011-10-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress.

  8. Clinical Analysis of Pulmonary Nocardiosis in Patients With Autoimmune Disease

    PubMed Central

    Li, Shan; Song, Xin yu; Zhao, Yu yue; Xu, Kai; Bi, Ya lan; Huang, Hui; Xu, Zuo jun

    2015-01-01

    Abstract Nocardiosis is an opportunistic infection that most commonly involves the lung; however, only a few case reports of autoimmune disease complicated by pulmonary nocardiosis exist in the literature. We conducted a retrospective analysis of 24 cases of both autoimmune disease and pulmonary nocardiosis at the Peking Union Medical College Hospital between 1990 and 2012. Fifty-two cases were hospitalized with nocardiosis, 24 of whom had at least 1 autoimmune disease before the diagnosis of pulmonary nocardiosis. The cohort patients consisted of 5 men and 19 women, with a mean age of 44.2 years. All were negative for human immunodeficiency virus. All but 1 patient had received immunosuppressants, including corticosteroids, cyclophosphamide, azathioprine, methotrexate, or hydroxychloroquine. Fever (87.5%), cough (83.3%), and sputum (79.2%) were the most common clinical manifestations. Ten cases were accompanied by subcutaneous nodules and/or cutaneous abscesses, and 4 had brain abscess. Half of them were lymphocytopenic. Thirteen of the 16 cases who underwent lymphocyte subtype analysis had decreased CD4+ T-cell counts. Nineteen cases had decreased serum albumin levels. Nocardia was isolated from sputum (13/24), bronchoalveolar lavage fluid (4/6), lung tissue (5/6), pleural effusions (3/5), skin or cutaneous pus (7/10), and brain tissue (1/1). The most common imaging findings were air-space opacities (83.3%), followed by nodules (62.5%), cavitations (45.8%), and masses (37.5%). Five were administered co-trimoxazole only, and the others were treated with 2 or more antibiotics. All 5 cases with skin abscesses and 2 of the 4 cases with brain abscesses were treated by surgical incision and drainage. None underwent thoracic surgery. Corticosteroid dosages were decreased in all cases, and cytotoxic agents were discontinued in some cases. Twenty-two cases recovered, and 2 died. Pulmonary nocardiosis associated with an underlying autoimmune disease showed a female

  9. Fulminant hepatic failure in autoimmune polyendocrine syndrome type-1.

    PubMed

    Sinha, R; Chapman, A R; Reid, G T; Hayes, P C

    2015-01-01

    Fulminant hepatic failure is liver disease that causes encephalopathy within 8 weeks of onset of symptoms or within 2 weeks of onset of jaundice in a patient without prior evidence of liver disease. Autoimmune polyendocrine syndrome type-1 is an autoimmune autosomal-recessive condition causing parathyroid and adrenal insufficiency, alopecia, chronic mucocutaneous candidiasis, ectodermal dystrophy and, rarely, hepatitis. Although the liver can be affected as a consequence of the autoimmune process, the spectrum of disease activity is varied. Autoimmune hepatitis develops in 10-20% of patients and successful liver transplantation has been reported in pediatric patients who failed immunosuppressive treatment. We report fulminant hepatic failure in an adult patient with autoimmune polyendocrine syndrome type-1 who responded to medical treatment and did not require liver transplantation. We highlight the diagnostic scoring system for autoimmune hepatitis and the referral criteria for liver transplantation in fulminant hepatic failure.

  10. Autoimmune thyroid disease and rheumatoid arthritis: relationship and the role of genetics.

    PubMed

    Lazúrová, Ivica; Jochmanová, Ivana; Benhatchi, Karim; Sotak, Stefan

    2014-12-01

    Autoimmune thyroid disease (AITD), known as the most common organ-specific autoimmune disorder, is frequently accompanied by other organ and non-organ-specific autoimmune diseases, including rheumatoid arthritis (RA). Although the exact pathogenic mechanisms of the coexistence of autoimmune disorders are still not completely defined, genetics, immune defects, hormones and environmental factors may play key roles in polyautoimmunity. In this review, the prevalence of AITD and antithyroid autoantibodies in RA patients and rheumatic manifestations in association with thyroid autoimmunity are discussed. Finally, we review the role of genetics in the association of both AITD and RA, especially CTLA-4 and PTPN22 polymorphisms.

  11. Autoantibodies in the diagnosis and management of liver disease.

    PubMed

    Czaja, Albert J; Norman, Gary L

    2003-10-01

    Autoantibodies are nonpathogenic manifestations of immune reactivity, and they may occur in acute and chronic liver diseases. Autoantibodies may be consequences rather than causes of the liver injury, and they should be regarded as diagnostic clues rather than etiologic markers. Conventional autoantibodies used in the categorization of autoimmune liver disease are antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, antimitochondrial antibodies, and atypical perinuclear anti-neutrophil cytoplasmic antibodies. Ancillary autoantibodies that enhance diagnostic specificity, have prognostic connotation, or direct treatment are antibodies to endomysium, tissue transglutaminase, histones, doubled-stranded DNA, and actin. Autoantibodies that have an emerging diagnostic and prognostic significance are antibodies to soluble liver antigen/liver pancreas, asialoglycoprotein receptor, liver cytosol type 1, and nuclear pore complex antigens. Autoantibodies of uncertain clinical value that remain under investigation are antibodies to chromatin, lactoferrin, and Saccharomyces cervisiae. Continued recognition and characterization of autoantibodies should improve diagnostic precision, provide prognostic indices, and elucidate target autoantigens. These advances may in turn clarify pathogenic mechanisms, facilitate the development of animal models, and generate novel site-specific therapies. PMID:14506390

  12. Alcoholic Liver Disease and Malnutrition

    PubMed Central

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2013-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy. PMID:21284673

  13. Respiratory Complication in Liver Disease.

    PubMed

    Ramalingam, Vijaya S; Ansari, Sikandar; Fisher, Micah

    2016-07-01

    Cirrhosis, the twelfth leading cause of death, accounts for 1.1% of all deaths in the United States. Although there are multiple pulmonary complications associated with liver disease, the most important complications that cause significant morbidity and mortality are hepatopulmonary syndrome, hepatic hydrothorax, and portopulmonary hypertension. Patients with cirrhosis who complain of dyspnea should be evaluated for these complications. This article reviews these complications. PMID:27339676

  14. Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases.

    PubMed

    Mayama, T; Marr, A K; Kino, T

    2016-08-01

    Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA "glucocorticoid response element (GRE)". To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA "GRE". Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy. PMID:27214311

  15. Cell-mediated immunity in idiopathic autoimmune haemolytic disease.

    PubMed Central

    Slavin, S; Aker, M; Plesser, Y M; Rachmilewitz, E A

    1975-01-01

    Membrane antigens from autologous and from allogeneic red blood cells (RBC) induced migration inhibition of splenic leucocytes and transformation of peripheral blood lymphocytes from a patient with idiopathic autoimmune haemolytic disease (AHD). No migration inhibition occurred following stimulation of splenic leucocytes obtained during splenectomy from a patient with beta-thalassaemia major. Lymphocyte transformation did not occur when normal lymphocytes were stimulated by similar RBC membrane preparations. These findings indicate that autosensitization in AHD may be a function of both humoral and cellular immune mechanisms. PMID:1204245

  16. Dementia associated with toxic causes and autoimmune disease.

    PubMed

    Schofield, Peter

    2005-01-01

    Toxic causes of dementia include exposure to heavy metals such as lead, mercury and aluminum as well as to carbon monoxide and solvents. Autoimmune conditions include such entities as multiple sclerosis, systemic lupus erythematosus, Behçet's disease and Sjögren's syndrome. These conditions share broadly similar cognitive effects giving rise to impairments with subcortical features. Individuals are often affected at a relatively young age. Optimal preventative strategies include avoidance of toxic substances. Comprehensive neuropsychological assessment is valuable not only diagnostically and for monitoring but also to identify the patients' strengths and weaknesses, so that compensatory strategies can be recommended.

  17. Autoimmune Thyroid Disease in Rheumatoid Arthritis: A Global Perspective

    PubMed Central

    Cárdenas Roldán, Jorge; Amaya-Amaya, Jenny; Castellanos-de la Hoz, Juan; Giraldo-Villamil, Juliana; Montoya-Ortiz, Gladys; Cruz-Tapias, Paola; Rojas-Villarraga, Adriana; Mantilla, Rubén D.; Anaya, Juan-Manuel

    2012-01-01

    Objective. To determine the prevalence and impact of autoimmune thyroid disease (AITD) in patients with rheumatoid arthritis (RA). Methods. Eight-hundred patients were included. The association between AITD and RA was analyzed was analyzed by bivariate and multivariate analysis. In addition, a literature review was done focusing on geographical variations. Results. In our cohort the prevalence of AITD was 9.8% while the presence of antibodies was 37.8% for antithyroperoxidase enzyme (TPOAb) and 20.8% for antithyroglobulin protein (TgAb). The presence of type 2 diabetes, thrombosis, abnormal body mass index, and a high educational level was positively associated with AITD. The literature review disclosed a geographical variation of AITD in RA ranging from 0.5% to 27%. Autoantibody prevalence ranges from 6% to 31% for TgAb, 5% to 37% for TPOAb, and from 11.4% to 32% for the presence of either of the two. Conclusion. AITD is not uncommon in RA and should be systematically assessed since it is a risk factor for developing diabetes and cardiovascular disease. These results may help to further study the common mechanisms of autoimmune diseases, to improve patients' outcome, and to define public health policies. An international consensus to accurately diagnose AITD is warranted. PMID:23209899

  18. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases

    PubMed Central

    Charlon, Thomas; Bossini-Castillo, Lara; Carmona, F. David; Di Cara, Alessandro; Wojcik, Jérôme; Voloshynovskiy, Sviatoslav

    2016-01-01

    Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this “ancestry signal”, we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust. PMID:27490238

  19. CD226 Gly307Ser association with multiple autoimmune diseases.

    PubMed

    Hafler, J P; Maier, L M; Cooper, J D; Plagnol, V; Hinks, A; Simmonds, M J; Stevens, H E; Walker, N M; Healy, B; Howson, J M M; Maisuria, M; Duley, S; Coleman, G; Gough, S C L; Worthington, J; Kuchroo, V K; Wicker, L S; Todd, J A

    2009-01-01

    Genome-wide association studies provide insight into multigenic diseases through the identification of susceptibility genes and etiological pathways. In addition, the identification of shared variants among autoimmune disorders provides insight into common disease pathways. We previously reported an association of a nonsynonymous single nucleotide polymorphism (SNP) rs763361/Gly307Ser in the immune response gene CD226 on chromosome 18q22 with type 1 diabetes (T1D) susceptibility. Here, we report efforts toward identifying the causal variant by exonic resequencing and tag SNP mapping of the 18q22 region in both T1D and multiple sclerosis (MS). In addition to the analysis of newly available samples in T1D (2088 cases and 3289 controls) and autoimmune thyroid disease (AITD) (821 cases and 1920 controls), resulting in strong support for the Ser(307) association with T1D (P=3.46 x 10(-9)) and continued potential evidence for AITD (P=0.0345), we provide evidence for association of Gly307Ser with MS (P=4.20 x 10(-4)) and rheumatoid arthritis (RA) (P=0.017). The Ser(307) allele of rs763361 in exon 7 of CD226 predisposes to T1D, MS, and possibly AITD and RA, and based on the tag SNP analysis, could be the causal variant. PMID:18971939

  20. Single Nucleotide Polymorphism Clustering in Systemic Autoimmune Diseases.

    PubMed

    Charlon, Thomas; Martínez-Bueno, Manuel; Bossini-Castillo, Lara; Carmona, F David; Di Cara, Alessandro; Wojcik, Jérôme; Voloshynovskiy, Sviatoslav; Martín, Javier; Alarcón-Riquelme, Marta E

    2016-01-01

    Systemic Autoimmune Diseases, a group of chronic inflammatory conditions, have variable symptoms and difficult diagnosis. In order to reclassify them based on genetic markers rather than clinical criteria, we performed clustering of Single Nucleotide Polymorphisms. However naive approaches tend to group patients primarily by their geographic origin. To reduce this "ancestry signal", we developed SNPClust, a method to select large sources of ancestry-independent genetic variations from all variations detected by Principal Component Analysis. Applied to a Systemic Lupus Erythematosus case control dataset, SNPClust successfully reduced the ancestry signal. Results were compared with association studies between the cases and controls without or with reference population stratification correction methods. SNPClust amplified the disease discriminating signal and the ratio of significant associations outside the HLA locus was greater compared to population stratification correction methods. SNPClust will enable the use of ancestry-independent genetic information in the reclassification of Systemic Autoimmune Diseases. SNPClust is available as an R package and demonstrated on the public Human Genome Diversity Project dataset at https://github.com/ThomasChln/snpclust. PMID:27490238

  1. Development of a disease registry for autoimmune bullous diseases: initial analysis of the pemphigus vulgaris subset.

    PubMed

    Shah, Amit Aakash; Seiffert-Sinha, Kristina; Sirois, David; Werth, Victoria P; Rengarajan, Badri; Zrnchik, William; Attwood, Kristopher; Sinha, Animesh A

    2015-01-01

    Pemphigus vulgaris (PV) is a rare, potentially life threatening, autoimmune blistering skin disease. The International Pemphigus and Pemphigoid Foundation (IPPF) has recently developed a disease registry with the aim to enhance our understanding of autoimmune bullous diseases with the long-term goal of acquiring information to improve patient care. Patients were recruited to the IPPF disease registry through direct mail, e-mail, advertisements, and articles in the IPPF-quarterly, -website, -Facebook webpage, and IPPF Peer Health Coaches to complete a 38-question survey. We present here the initial analysis of detailed clinical information collected on 393 PV patients. We report previously unrecognized gender differences in terms of lesion location, autoimmune comorbidity, and delay in diagnosis. The IPPF disease registry serves as a useful resource and guide for future clinical investigation. PMID:24691863

  2. Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

    PubMed Central

    Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

    2016-01-01

    Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids

  3. An unusual association of three autoimmune disorders: celiac disease, systemic lupus erythematosus and Hashimoto's thyroiditis.

    PubMed

    Boccuti, Viera; Perrone, Antonio; D'Introno, Alessia; Campobasso, Anna; Sangineto, Moris; Sabbà, Carlo

    2016-12-01

    Autoimmune disorders are known to be more frequent in women and often associated each others, but it is rare to see multiple autoimmune diseases in a single patient. Recently, the concept of multiple autoimmune syndrome has been introduced to describe patients with at least three autoimmune diseases. We describe a case of a young man with a clinical history of psychiatric symptoms and celiac disease (CD) who was diagnosed to have other two autoimmune disorders: systemic lupus erythematosus (SLE) and Hashimoto's thyroiditis. This case is unusual upon different patterns: the rare combination of the three autoimmune diseases, their appearance in a man and the atypical onset of the diseases with psychiatric symptoms likely to be related either to CD or to SLE. PMID:27383232

  4. [Polycystic liver disease without autosomal dominant polycystic kidney disease].

    PubMed

    Peces, R; González, P; Venegas, J L

    2003-01-01

    Polycystic liver disease is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. The natural history and clinical manifestations of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The occurrence of polycystic liver disease independently from polycystic kidney disease has been known for a long time. More recently, a gene for autosomal dominant polycystic liver disease has been identified on chromosome 19p 13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis and clinical manifestations. We report here two men with polycystic liver disease no associated with ADPKD. Ultrasound and computed tomography imaging were effective in documenting the underlying lesions non-invasively.

  5. Autoimmune pancreatitis: an underdiagnosed autoimmune disease with clinical, imaging and serological features.

    PubMed

    Sánchez-Castañón, María; de las Heras-Castaño, Gonzalo; López-Hoyos, Marcos

    2010-02-01

    Since Sarles et al. [Sarles H, Sarles JC, Muratore R, Guien C. Chronic inflammatory sclerosis of the pancreas-an autonomous pancreatic disease? Am J Dig Dis 1961; 6: 688-698.] reported a case of pancreatitis associated with hypergammaglobulinemia, many cases have been described, which led to the current concept of "autoimmune pancreatitis (AIP)". Lymphoplasmacytic infiltration and fibrosis on histology together with elevated IgG levels or the presence of autoantibodies on laboratory examinations supported the concept of AIP. In recent years, based on histological and immunohistochemical examination of various organs of patients with AIP, a novel clinicopathological entity, IgG4-related slerosing disease, has been proposed. AIP is a systemic disease that is characterized by dense infiltration of IgG4-positive plasma cells and T lymphocytes in various organs. Clinical manifestations are related with pancreas dysfunction but other organs may be affected such as bile duct, gallbladder, salivary gland, retroperitoneum, kidney, lung and prostate. Increased serum IgG4 levels, the presence of several autoantibodies such as anti-carbonic anhydrase II antibodies (ACA-II), immunostaining IgG4 positive in pancreas tissue and a very good response to steroid therapy are useful for the diagnosis of AIP that can mimic pancreatic cancer.

  6. Autoimmune pancreatitis and IgG4-related systemic diseases

    PubMed Central

    Zhang, Lizhi; Smyrk, Thomas C

    2010-01-01

    Autoimmune pancreatitis (AIP) is a rare form of chronic pancreatitis that is characterized by lymphoplasmacytic infiltrate, storiform fibrosis, obliterative phlebitis, and increased IgG4+ plasma cells. Serum IgG4 levels usually are elevated. Patients with AIP frequently have disease affecting other organs or sites; these tissues show similar histologic changes, including increased IgG4+ plasma cell infiltrate and response to corticosteroid therapy. A new clinicopathologic concept of IgG4-related systemic disease (ISD) has been proposed. These diseases often are not limited to the pancreas, and the pancreas may not be involved at all. In this article, we review the literature and our own experience to detail the clinicopathologic features of AIP and extrapancreatic lesions in ISD. PMID:20606730

  7. Porous silicon biosensor for the detection of autoimmune diseases

    NASA Astrophysics Data System (ADS)

    Jane, Andrew O.; Szili, Endre J.; Reed, Joanne H.; Gordon, Tom P.; Voelcker, Nicolas H.

    2007-12-01

    Advances in porous silicon (pSi) technology have led to the development of new sensitive biosensors. The unique optical properties of pSi renders the material a perfect candidate for optical transducers exploiting photoluminescence or white light interference effects. The ability of biosensors exploiting these transduction mechanisms to quickly and accurately detect biological target molecules affords an alternative to current bioassays such as enzyme-linked immunosorbent assays (ELISAs). Here, we present a pSi biosensor that was developed to detect antibodies against the autoimmune protein La. This protein is associated with autoimmune diseases including rheumatic disorders, systematic lupus erythematosus (SLE) and Sjogren's syndrome (SS). A fast and sensitive detection platform such as the one described here can be applied to the rapid diagnosis of these debilitating autoimmune diseases. The immobilisation of the La protein onto pSi films gave a protein receptor-decorated sensor matrix. A cascade of immunological reactions was then initiated to detect anti-La antibody on the functionalised pSi surface. In the presence of o-phenylenediamine (OPD), horseradish peroxidase (HRP)/H IIO II catalysed the formation of an oxidised radical species that accelerated pSi corrosion. pSi corrosion was detected as a blue-shift in the generated interference pattern, corresponding to a decrease in the effective optical thickness (EOT) of the pSi film. Compared to an ELISA, the pSi biosensor could detect the anti-La antibody at a similar concentration (500 - 125 ng/ml). Furthermore, we found that the experimental process can be significantly shortened resulting in detection of the anti-La antibody in 80 minutes compared to a minimum of 5 hours required for ELISA.

  8. Identification of antigenic proteins associated with trichloroethylene-induced autoimmune disease by serological proteome analysis

    SciTech Connect

    Liu Jianjun; Xing Xiumei; Huang Haiyan; Jiang Yingzhi; He Haowei; Xu Xinyun; Yuan Jianhui; Zhou Li; Yang Linqing; Zhuang Zhixiong

    2009-11-01

    Although many studies indicated that trichloroethylene (TCE) could induce autoimmune diseases and some protein adducts were detected, the proteins were not identified and mechanisms remain unknown. To screen and identify autoantigens which might be involved in TCE-induced autoimmune diseases, three groups of sera were collected from healthy donors (I), patients suffering from TCE-induced exfoliative dermatitis (ED) (II), and the healed ones (III). Serological proteome analysis (SERPA) was performed with total proteins of TCE-treated L-02 liver cells as antigen sources and immunoglobins of the above sera as probes. Highly immunogenic spots (2-fold or above increase compared with group I) in group II and III were submitted to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and tandem mass spectrometry sequencing. Western blot analysis was followed using commercial antibodies and individual serum. Six proteins were identified. Among them, Enoyl Coenzyme A hydratase peroxisoma 1 and lactate dehydrogenase B only showed stronger immunogenicity for group II sera, while Purine nucleoside phosphorylase, ribosomal protein P0 and proteasome activator subunit1 isoform1 also showed stronger immunogenicity for group III sera. Noteworthy, NM23 reacted only with group II sera. Western blot analysis of NM23 expression indicated that all of the individual serum of group II showed immune activity, which confirmed the validity of SERPA result. These findings revealed that there exist autoantibodies in group II and III sera. Besides, autoantibodies of the two stages of disease course were different. These autoantigens might serve as biomarkers to elucidate mechanisms underlying TCE toxicity and are helpful for diagnosis, therapy and prognosis of TCE-induced autoimmune diseases.

  9. [Ulcerative colitis associated with autoimmune hepatitis: a differential form of inflammatory bowel disease?].

    PubMed

    Giraldo Escobar, L M; Crespo Madrid, N; Vila Miravet, V; Pujol Muncunill, G; Varea Calderón, V; Martín de Carpi, J

    2015-01-01

    Inflammatory bowel Disease (IBD) is a group of chronic inflammatory diseases that can be associated with different autoimmune diseases, including autoimmune hepatitis (AIH). Some specific and differential characteristics in children with IBD associated to AIH have been described. Our aim is to describe the clinical pattern of this association observed in our patients, confirming its differential characteristics as compared to classical IBD in children.

  10. CYP2E1 autoantibodies in liver diseases.

    PubMed

    Sutti, Salvatore; Rigamonti, Cristina; Vidali, Matteo; Albano, Emanuele

    2014-01-01

    Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression.

  11. Treatment of alcoholic liver disease.

    PubMed

    Barve, Ashutosh; Khan, Rehan; Marsano, Luis; Ravindra, Kadiyala V; McClain, Craig

    2008-01-01

    Alcoholic Liver Disease (ALD) is a major cause of morbidity and mortality both in the United States and worldwide. In the United States, it is projected that over 2,000,000 persons have ALD, and the mortality for cirrhosis with superimposed alcoholic hepatitis is much worse than that of many common types of cancer. Unfortunately, there is no FDA approved therapy for ALD. We have made major strides in the last decade in identifying mechanisms for the development of liver injury in ALD, and therapies are evolving directed at specific mechanisms. It is clear that life style modification with abstinence, cessation of smoking and weight loss (if overweight) are beneficial. It is also clear that most patients with advanced liver disease have some form of malnutrition, and nutritional supplementation is of benefit. Patients with alcoholic hepatitis that is relatively severe in nature, but not complicated by issues such as infection or GI bleeding, appear to benefit from steroids. A drop in bilirubin should be monitored in steroid treated patients. Pentoxifylline appears to be beneficial in patients with alcoholic hepatitis, especially those with early hepatorenal syndrome. A variety of other agents such as PTU, lecithin, colchicine, and anabolic steroids are probably not effective. Complementary and alternative medicine agents such as zinc, milk thistle, and SAM have great therapeutic rationale. Results of ongoing NIH studies evaluating agents such as specific anti-TNF's, SAM and Milk Thistle are eagerly awaited. Transplantation is clearly an option for end stage ALD in patients who are abstinent.

  12. Encephalopathy Associated with Autoimmune Thyroid Disease: A Potentially Reversible Condition

    PubMed Central

    Correia, Inês; Marques, Inês B.; Ferreira, Rogério; Sousa, Lívia

    2016-01-01

    Autoimmune thyroid disease may occasionally associate with unspecific neurological symptoms, which are more commonly insidious, include cognitive or behavioural symptoms, and may associate with tremor, myoclonus, or ataxia. We report a 61-year-old female patient who presented with chronic headache, insidious mood, and cognitive disturbance which evolved in a few months to dementia associated with exuberant limb myoclonus. Diagnostic workup revealed high anti-thyroid peroxidase antibody titers and an inflammatory CSF profile, and it was negative for other possible etiologies. Treatment with steroids induced significant improvement. The diagnosis of encephalopathy associated with autoimmune thyroid disease is still controversial given the fact that the clinical presentation and diagnostic workup are unspecific, the pathophysiology is still undetermined, and the diagnosis is mostly of exclusion. No direct correlation is found between anti-thyroid antibody titers and clinical presentation, and it is currently speculated that other still unrecognized antibodies may be responsible for this clinical entity. It is extremely important to recognize this entity because it is potentially treatable with immunotherapies. It is also increasingly recognized that clinical improvement with first-line treatment with steroids may be absent or incomplete, and other immunotherapies as immunosuppressants, intravenous immunoglobulin, or plasma exchange must be attempted in the clinical suspicion of EEAT. PMID:27127515

  13. New Platform Technology for Comprehensive Serological Diagnostics of Autoimmune Diseases

    PubMed Central

    Willitzki, Annika; Hiemann, Rico; Peters, Vanessa; Sack, Ulrich; Schierack, Peter; Rödiger, Stefan; Anderer, Ursula; Conrad, Karsten; Bogdanos, Dimitrios P.; Reinhold, Dirk; Roggenbuck, Dirk

    2012-01-01

    Antibody assessment is an essential part in the serological diagnosis of autoimmune diseases. However, different diagnostic strategies have been proposed for the work up of sera in particular from patients with systemic autoimmune rheumatic disease (SARD). In general, screening for SARD-associated antibodies by indirect immunofluorescence (IIF) is followed by confirmatory testing covering different assay techniques. Due to lacking automation, standardization, modern data management, and human bias in IIF screening, this two-stage approach has recently been challenged by multiplex techniques particularly in laboratories with high workload. However, detection of antinuclear antibodies by IIF is still recommended to be the gold standard method for antibody screening in sera from patients with suspected SARD. To address the limitations of IIF and to meet the demand for cost-efficient autoantibody screening, automated IIF methods employing novel pattern recognition algorithms for image analysis have been introduced recently. In this respect, the AKLIDES technology has been the first commercially available platform for automated interpretation of cell-based IIF testing and provides multiplexing by addressable microbead immunoassays for confirmatory testing. This paper gives an overview of recently published studies demonstrating the advantages of this new technology for SARD serology. PMID:23316252

  14. Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

    PubMed Central

    Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

    2014-01-01

    Abstract The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

  15. Targeting of type I interferon in systemic autoimmune diseases.

    PubMed

    Crow, Mary K; Olferiev, Mikhail; Kirou, Kyriakos A

    2015-02-01

    Increased blood levels of type I interferon (IFN-I) and expression of a broad signature of gene transcripts that reflect induction by IFN-I are observed in many patients with systemic autoimmune diseases, and that pattern is most striking in systemic lupus erythematosus (SLE). Persistent production of IFN-α, the most abundant subtype measured in these patients, is an important feature of the immunopathogenesis of lupus and has stimulated current efforts to develop and test therapeutics that either block IFN-I or its receptor directly or target components of the IFN-I pathway involved in induction of or response to IFN-I. In this review data from animal models of chronic viral infection, examples of lupus-like syndromes associated with single-gene mutations that impact the IFN-I pathway, and longitudinal studies of patients with lupus are described and support the rationale for therapeutic targeting of the IFN-I pathway. However, the complexity of IFN-I regulation and the diversity of its effects on immune system function suggest that the definitive demonstration of that pathway as a valid and productive therapeutic target will only come from clinical trials of agents tested in patients with systemic autoimmune disease, with patients with lupus likely to be the most informative.

  16. FOXP3+ Treg Cells and Gender Bias in Autoimmune Diseases

    PubMed Central

    Nie, Jia; Li, Yang Yang; Zheng, Song Guo; Tsun, Andy; Li, Bin

    2015-01-01

    CD4+CD25+ regulatory T (Treg) cells play a pivotal role in the maintenance of immune homeostasis, where the X-linked master transcription factor forkhead box P3 (FOXP3) determines Treg cell development and function. Genetic deficiency of foxp3 induces dysfunction of Treg cells and immuno-dysregulation, polyendocrinopathy, enteropathy, and X-linked syndrome in humans. Functionally deficient Treg cells or the development of exTreg cells positively correlate with autoimmune diseases, such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), and ankylosing spondylitis (AS). In general, females are more susceptible to SLE and MS but less susceptible to AS, where the expression of FOXP3 and its protein complex are perturbed by multiple factors, including hormonal fluctuations, inflammatory cytokines, and danger signals. Therefore, it is critical to explore the potential molecular mechanisms involved and these differences linked to gender. Here, we review recent findings on the regulation of FOXP3 activity in Treg cells and also discuss gender difference in the determination of Treg cell function in autoimmune diseases. PMID:26441996

  17. JAKpot! New small molecules in autoimmune and inflammatory diseases

    PubMed Central

    Ghoreschi, Kamran; Gadina, Massimo

    2013-01-01

    Cytokines are key mediators of the development and homeostasis of hematopoietic cells, critical for host defense, but also for the development of autoimmune and inflammatory diseases like psoriasis or rheumatoid arthritis (RA). Blocking cytokines activity by interfering with the ligand-receptor association has been successfully employed to treat several immune disorders. A subgroup of cytokines signals through receptors requiring the association with a family of cytoplasmic protein tyrosine kinases known as Janus kinases (Jaks). Jaks have recently gained significant attention as therapeutic targets in inflammation and autoimmunity and several Jak inhibitory small molecules have been developed. The first two Jak inhibitors, tofacitinib and ruxolitinib, have been approved for the treatment of RA and primary myelofibrosis, respectively. Efficacy and safety data suggest that some of these oral Jak inhibitors as well as their topical formulations may soon enter the daily clinical practice for treating patients with psoriasis, lupus erythematosus or other inflammatory skin diseases. While biologics typically target one single cytokine, these new immunomodulators can inhibit signals from multiple cytokines intracellularly and therefore could be useful when other therapies are ineffective. Thus, Jak inhibitors may replace some traditional immunosuppressive agents and help patients not responding to previous therapies. PMID:24131352

  18. The skin in autoimmune diseases-Unmet needs.

    PubMed

    Kuhn, A; Landmann, A; Bonsmann, G

    2016-10-01

    Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations. PMID:27481041

  19. The skin in autoimmune diseases-Unmet needs.

    PubMed

    Kuhn, A; Landmann, A; Bonsmann, G

    2016-10-01

    Treatment of skin manifestations in systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and dermatomyositis (DM) is based on the results of only few randomized controlled trials. The first-line treatment for disfiguring and widespread cutaneous involvement in SLE is antimalarials, but some patients are therapy resistant. Recently, the monoclonal antibody belimumab was approved for SLE as an adjunct therapy for patients with autoantibody-positive disease who despite standard therapy show high disease activity, intolerance of other treatments, or an unacceptably high need for corticosteroids. However, a validated skin score has not been used to confirm the efficacy of belimumab on mucocutaneous manifestations. In SSc, another multi-systemic progressive disease, involvement of the lung, kidney, and the heart is frequently treated with corticosteroids and immunosuppressives, but therapeutic modalities for cutaneous lesions, such as skin sclerosis and digital ulcers, are limited. In the past years, treatment with the endothelin-receptor antagonist bosentan has been proven to reduce the occurrence of new digital ulcers in SSc patients but has no or limited effect on healing of digital ulcers. DM is an idiopathic autoimmune disease characterized by inflammation of the muscles and skin, which is treated with immunosuppressives. Corticosteroids are the first-line treatment for muscle involvement in DM, but skin lesions often flare by reduction or discontinuation. In summary, there is a high unmet need for new therapeutic strategies focusing on skin involvement in systemic autoimmune diseases. Therefore, innovative designs of randomized controlled trials with validated skin scores are warranted to develop new therapeutic strategies for patients with cutaneous manifestations.

  20. The microbiome and autoimmune disease: Report from a Noel R. Rose Colloquium.

    PubMed

    Barin, Jobert G; Tobias, Lawrence D; Peterson, Daniel A

    2015-08-01

    Although the mechanisms by which the human microbiome influences the onset and progression of autoimmune diseases remain to be determined, established animal models of autoimmune diseases indicate that local and systemic bidirectional interactions with the microbiome play a signaling or promoting role through the immune system. Whether alterations in the microbiome are a pathogenic cause or simply an effect of inflammation and autoimmune disease remains an essential question to be addressed in disease-specific research, as well as whether particular conditions of the microbiome promote health or promote disease. Future research in this area needs to account for sex differences in microbiome composition because autoimmune diseases disproportionately affect women. Probiotic and other treatments that manipulate assemblage of the microbiome may offer methods of preventing or mitigating the effects of autoimmune disease.

  1. Comparative genomics for the investigation of autoimmune diseases.

    PubMed

    Möller, Steffen; Zettl, Uwe K; Serrano-Fernández, Pablo; Goertsches, Robert

    2006-01-01

    The complete DNA sequence of the human genome and of several related mammals are now available, due to the investments of enormous resources and advances in sequencing technology. Novel technologies have been developed to compare multiple genomes with each other, thus specifying regions of sequence similarity among mammals and with their pathogens. Larger blocks of sequence similarity (syntenic regions) have been determined and made publicly available. In many ways, novel insights can be gained by such data when combining external genetic or clinical information for these syntenic loci. These novel tools have proven to be successful in inferring functional equivalence between loci of multiple genomes. This review reports on the role of comparative genomics in research on autoimmune diseases, a field with strong dependencies on animal models of human diseases and the problem of an adequate information transfer between multiple organisms and research areas. PMID:17073670

  2. Genetic homogeneity of autoimmune polyglandular disease type I

    SciTech Connect

    Bjoerses, P.; Aaltonen, J.; Vikman, A.

    1996-10-01

    Autoimmune polyglandular disease type I (APECED) is an autosomal recessive autoimmune disease (MIM 240300) characterized by hypoparathyroidism, primary adrenocortical failure, and chronic mucocutaneous candidiasis. The disease is highly prevalent in two isolated populations, the Finnish population and the Iranian Jewish one. Sporadic cases have been identified in many other countries, including almost all European countries. The APECED locus has previously been assigned to chromosome 21q22.3 by linkage analyses in 14 Finnish families. Locus heterogeneity is a highly relevant question in this disease affecting multiple tissues and with great phenotypic diversity. To solve this matter, we performed linkage and haplotype analyses on APECED families rising from different populations. Six microsatellite markers on the critical chromosomal region of 2.6 cM on 21q22.3 were analyzed. Pair-wise linkage analyses revealed significant LOD scores for all these markers, maximum LOD score being 10.23. The obtained haplotype data and the geographic distribution of the great-grandparents of the Finnish APECED patients suggest the presence of one major, relatively old mutation responsible for {approximately}90% of the Finnish cases. Similar evidence for one founder mutation was also found in analyses of Iranian Jewish APECED haplotypes. These haplotypes, however, differed totally from the Finnish ones. The linkage analyses in 21 non-Finnish APECED families originating from several European countries provided independent evidence for linkage to the same chromosomal region on 21q22.3 and revealed no evidence for locus heterogeneity. The haplotype analyses of APECED chromosomes suggest that in different populations APECED is due to a spectrum of mutations in a still unknown gene on chromosome 21. 21 refs., 3 figs., 3 tabs.

  3. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease: A Retrospective Study of 10 Cases.

    PubMed

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-07-01

    The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined.We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens.The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating.Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN.

  4. Role of the MHC2TA gene in autoimmune diseases

    PubMed Central

    Martínez, Alfonso; Sánchez‐Lopez, Marta; Varadé, Jezabel; Mas, Ana; Martín, M Carmen; de las Heras, Virginia; Arroyo, Rafael; Mendoza, Juan Luis; Díaz‐Rubio, Manuel; Fernández‐Gutiérrez, Benjamín; de la Concha, Emilio G; Urcelay, Elena

    2007-01-01

    Objectives Expression of major histocompatibility complex (MHC) class II genes is almost exclusively regulated by the class II transactivator. A promoter polymorphism (−168A/G, rs3087456) in the MHC2TA gene was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction in a northern European population. However, no evidence of association of this MHC2TA variant with the two autoimmune diseases could be subsequently detected in independent cohorts. Aim To test the aforementioned single nucleotide polymorphism and another G→C change (nt1614 from coding sequence, rs4774) to analyse the haplotype pattern in this MHC2TA gene. Methods A case–control study was performed with 350 patients with rheumatoid arthritis, 396 patients with multiple sclerosis, 663 patients with inflammatory bowel disease (IBD) and 519 healthy controls from Madrid. Genotyping was ascertained by using TaqMan assays‐on‐demand on a 7900HT analyser, following the manufacturer's suggestions (Applied Biosystems, Foster City, California, USA). Haplotypes were inferred with the expectation–maximisation algorithm implemented by the Arlequin software. Results No independent association with these autoimmune diseases was found for either polymorphism in the Spanish cohorts tested. However, when haplotypes were compared between patients with rheumatoid arthritis and controls, a significant difference in their overall frequency distribution was observed, evidencing a protective haplotype (−168A/1614C, p = 0.006; odds ratio (OR) 0.7) and a risk haplotype (−168G/1614C, p = 0.019; OR 1.6). Patients with multiple sclerosis mirrored these results, but no effect on IBD was identified. Conclusions The MHC2TA gene influences predisposition to rheumatoid arthritis and multiple sclerosis, but not to IBD. The −168G allele is not an aetiological variant in itself, but a genetic marker of susceptibility/protection haplotypes. PMID:17012290

  5. Effects of Latent Toxoplasmosis on Autoimmune Thyroid Diseases in Pregnancy

    PubMed Central

    Kaňková, Šárka; Procházková, Lucie; Flegr, Jaroslav; Calda, Pavel; Springer, Drahomíra; Potluková, Eliška

    2014-01-01

    Background Toxoplasmosis, one of the most common zoonotic diseases worldwide, can induce various hormonal and behavioural alterations in infected hosts, and its most common form, latent toxoplasmosis, influences the course of pregnancy. Autoimmune thyroid diseases (AITD) belong to the well-defined risk factors for adverse pregnancy outcomes. The aim of this study was to investigate whether there is a link between latent toxoplasmosis and maternal AITD in pregnancy. Methods Cross-sectional study in 1248 consecutive pregnant women in the 9–12th gestational weeks. Serum thyroid-stimulating hormone (TSH), thyroperoxidase antibodies (TPOAb), and free thyroxine (FT4) were assessed by chemiluminescence; the Toxoplasma status was detected by the complement fixation test (CFT) and anti-Toxoplasma IgG enzyme-linked immunosorbent assay (ELISA). Results Overall, 22.5% of the women were positive for latent toxoplasmosis and 14.7% were screened positive for AITD. Women with latent toxoplasmosis had more often highly elevated TPOAb than the Toxoplasma-negative ones (p = 0.004), and latent toxoplasmosis was associated with decrease in serum TSH levels (p = 0.049). Moreover, we found a positive correlation between FT4 and the index of positivity for anti-Toxoplasma IgG antibodies (p = 0.033), which was even stronger in the TPOAb-positive Toxoplasma-positive women, (p = 0.014), as well as a positive correlation between FT4 and log2 CFT (p = 0.009). Conclusions Latent toxoplasmosis was associated with a mild increase in thyroid hormone production in pregnancy. The observed Toxoplasma-associated changes in the parameters of AITD are mild and do not seem to be clinically relevant; however, they could provide new clues to the complex pathogenesis of autoimmune thyroid diseases. PMID:25350671

  6. Nonalcoholic fatty liver disease and cardiovascular disease.

    PubMed

    Liu, Hong; Lu, Hong-Yun

    2014-07-14

    Nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD) are two diseases that are common in the general population. To date, many studies have been conducted and demonstrate a direct link between NAFLD and CVD, but the exact mechanisms for this complex relationship are not well established. A systematic search of the PubMed database revealed that several common mechanisms are involved in many of the local and systemic manifestations of NAFLD and lead to an increased cardiovascular risk. The possible mechanisms linking NAFLD and CVD include inflammation, oxidative stress, insulin resistance, ectopic adipose tissue distribution, dyslipidemia, endothelial dysfunction, and adiponectin, among others. The clinical implication is that patients with NAFLD are at an increased risk of CVD and should undergo periodic cardiovascular risk assessment. PMID:25024598

  7. Autoimmune disease and vaccination: impact on infectious disease prevention and a look at future applications.

    PubMed

    McKinnon, John E; Maksimowicz-McKinnon, Kathleen

    2016-01-01

    Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs. In addition, vaccine therapy is currently under study for the treatment of autoimmune disorders, with early studies demonstrating immunomodulatory effects that may counter undesired immune activation and alleviate disease activity.

  8. Infectious serologies and autoantibodies in hepatitis C and autoimmune disease-associated mixed cryoglobulinemia.

    PubMed

    Lidar, Merav; Lipschitz, Noga; Agmon-Levin, Nancy; Langevitz, Pnina; Barzilai, Ori; Ram, Maya; Porat-Katz, Bat-Sheba; Bizzaro, Nicola; Damoiseaux, Jan; Tervaert, Jan Willem Cohen; deVita, Salvatore; Bombardieri, Stefano; Shoenfeld, Yehuda

    2012-04-01

    Mixed cryoglobulinemia (MC) syndrome is an immune complex-mediated vasculitis characterized by the clinical triad of purpura, weakness, and arthralgias, the morbidity of which is mainly related to kidney and peripheral nervous system dysfunction as well as to the development of a secondary lymphoma (Ferri et al. Autoimmun Rev 7:114-120, 2007, Lidar et al. Ann N Y Acad Sci 1173:649-657, 2009, Trejo et al. Semin Arthritis Rheum 33:19-28, 2003). MC is associated with infectious and systemic disorders, principally autoimmune and lymphoproliferative diseases. Since the 1990s, a striking association (>90%) between MC and hepatitis C virus (HCV) infection has been established (Ferri and Bombardieri 2004; Pascual et al. J Infect Dis 162:569-570, 1990). However, information regarding the etiopathogenesis of HCV-negative MC is scant (Mascia et al. Dig Liver Dis 39:61-64, 2007). We hereby present our findings, as well as previously published data, regarding the presence of antibodies against infectious agents and autoantibodies in patients with MC in an attempt to establish novel associations which may shed light on the etiopathogenesis of this disease.

  9. Green tea EGCG, T cells, and T cell-mediated autoimmune diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the proposed health benefits of consuming green tea is its protective effect on autoimmune diseases. Research on the immunopathogenesis of autoimmune diseases has made significant progression in the past few years and several key concepts have been revised. T cells, particularly CD4+ T helper...

  10. Pregnancy in patients with autoimmune disease: A reality in 2016.

    PubMed

    Tincani, A; Dall'Ara, F; Lazzaroni, M G; Reggia, R; Andreoli, L

    2016-10-01

    Autoimmune rheumatic diseases are chronic systemic conditions often affecting young women during their reproductive years, so that pregnancy is a major issue in their management. For a long time pregnancy has been discouraged in these women, mainly for two reasons: gestation could aggravate maternal disease and, vice versa, the disease could negatively influence the gestational outcome. The great improvement in the approach to pregnancy done in the past few decades has allowed a progressively increasing number of affected women to fulfill their family plan. Women should be informed about potential risks related to their disease, but they should also be reassured that a good pregnancy outcome is possible if conception occurs in a stable remission state, teratogenic medications have been properly withdrawn and "safe" drugs have been mantained to prevent disease flare. A brief excursus regarding the main issues regarding SLE/APS, Systemic Sclerosis and Systemic Vasculitis is provided, in the attempt to delineate the main risk factors for adverse pregnancy outcome, the onset of maternal complications and the role played by a close multi-specialistic monitoring.

  11. Cancer Risk in Patients With Inflammatory Systemic Autoimmune Rheumatic Diseases

    PubMed Central

    Yu, Kuang-Hui; Kuo, Chang-Fu; Huang, Lu Hsiang; Huang, Wen-Kuan; See, Lai-Chu

    2016-01-01

    Abstract The aim of this study was to determine whether inflammation is related to cancer development, and whether the incidence of cancer is increased and occurs in a site-specific manner in patients with systemic autoimmune rheumatic diseases (SARDs). This study included a nationwide dynamic cohort of patients with various newly diagnosed SARDs from 1997 to 2010 with follow-up until 2012. This study included 75,123 patients with SARDs. During 562,870 person-years of follow-up, 2844 patients developed cancer. Between 1997 and 2010, the highest number of newly diagnosed SARDs cases were rheumatoid arthritis (n = 35,182), followed by systemic lupus erythematosus (SLE, n = 15,623), Sjögren syndrome (n = 11,998), Kawasaki disease (n = 3469), inflammatory bowel disease (n = 2853), scleroderma (n = 1814), Behçet disease (n = 1620), dermatomyositis (n = 1119), polymyositis (n = 811), and vasculitis other than Kawasaki disease (n = 644). A significant standardized incidence ratio (SIR) of overall cancer was observed for patients with SLE (1.41; 95% confidence interval [CI], 1.28–1.56), Sjögren syndrome (1.19; 95% CI, 1.08–1.30), scleroderma (1.27; 95% CI, 1.02–1.59), dermatomyositis (4.79; 95% CI, 4.01–5.73), polymyositis (1.47; 95% CI, 1.05–2.06), vasculitis excluding Kawasaki disease (1.75; 95% CI, 1.20–2.55), and Kawasaki disease (2.88; 95% CI, 1.60–5.20). Overall, patients with most SARDs had a significantly higher risk of inflammation-associated site-specific cancers and hematologic malignancies. This study confirms that autoimmunity is associated with site-specific and hematological malignancies and provides clinical evidence of an association between inflammation and subsequent site-specific cancer development. These findings support the importance of inflammation in site-specific organ system carcinogenesis. PMID:27149461

  12. Pros and cons of stem cell transplantation for autoimmune disease.

    PubMed

    Thomas, E D

    1997-05-01

    The data and discussion at this symposium have provided a most useful analysis of the autoimmune diseases and their potential for therapy by stem cell transplantation. These diseases are characterized by threat to life and particularly by chronic, painful and debilitating courses that warrant aggressive therapy. Selection of patients will be difficult because of the variable disease course and the necessity to choose patients who still have reversible disease. The safety of both autologous and allogeneic stem cell grafting has progressed to the point where, in many cases, the risks of the disease far outweigh those of transplantation. In my opinion the data presented at this symposium show that we should proceed cautiously with both autologous and allogeneic stem cell grafts. Purified stem cells, which have the advantage of being free of lymphocytes, should be used for the first series of autologous studies. These studies are attractive because of the low risk of transplant related complications but are less likely to be curative. Allogeneic grafts from perfectly matched donors have the advantage of providing a completely new immunological environment. For this reason, I believe that curative results are most probable after allogeneic stem cell engraftment. Emphasis should be on the identification of patients with HLA matched siblings. Initially, these studies will be carried out in patients with advanced disease, as was the case in the early days of transplantation for leukemia. In considering more aggressive treatment for autoimmune diseases it appears there are 3 possible approaches. First, and most conservative, is to store peripheral blood stem cells for possible future marrow rescue and then to give higher doses of immunosuppressive agents, especially in combination, to see whether there is an improvement over conventional doses. Second, for those who prefer a conservative approach to stem cell transplantation, is to give myeloablative and lymphoablative

  13. Argininosuccinate lyase: a new autoantigen in liver disease.

    PubMed

    Pelli, N; Fensom, A H; Slade, C; Boa, F; Mieli-Vergani, G; Vergani, D

    1998-12-01

    Anti-liver cytosol 1 autoantibody (LC1) characterizes a severe form of autoimmune hepatitis (AIH), staining the cytoplasm of periportal hepatocytes and targeting an unidentified 60-kD liver cytosolic antigen. To identify its target, we used high-titre anti-LCI+ sera from two patients with AIH to screen 18 cytoplasm enzymes with periportal location by double immunodiffusion (DDI). Both sera gave a broad precipitin line against human liver cytosol, suggesting that they may recognize two distinct antigens, a possibility confirmed by the appearance of two precipitin lines when DDI conditions were optimized (0.8% agarose and 3% polyethylene glycol (PEG)). Experiments by DDI and Western blot (WB) identified a liver cytosolic autoantigen of 50 kD, different from LC1, giving a line of identity with argininosuccinate lyase (ASL). Reactivity to ASL was then investigated by DDI and WB in 57 patients with AIH, 17 with primary biliary cirrhosis (PBC), 15 with chronic hepatitis B virus (HBV) infection, 13 with alphal-antitrypsin deficiency, 17 with Wilson's disease, 18 with extrahepatic autoimmune disorders, and in 48 healthy controls. Anti-ASL was found in 16% of AIH and 23% of PBC patients by DDI and in 14% of AIH, 23% of PBC and 20% of HBV patients by WB. No argininosuccinate was present in the urine of four anti-ASL+ patients tested, excluding an inhibition of enzymatic activity by anti-ASL. The addition of anti-ASL+ serum to human fibroblast cultures induced a significant increase in ASL activity. ASL is a new autoantigen in liver disease and its clinical relevance warrants further investigation.

  14. Immune Tolerance for Autoimmune Disease and Cell Transplantation

    PubMed Central

    Luo, Xunrong; Miller, Stephen D.; Shea, Lonnie D.

    2016-01-01

    The undesired destruction of healthy cells, either endogenous or transplanted, by the immune system results in the loss of tissue function or limits strategies to restore tissue function. Current therapies typically involve non-specific immunosuppression that may prevent the appropriate response to an antigen, thereby decreasing humoral immunity and increasing the risks of patient susceptibility to opportunistic infections, viral reactivation, and neoplasia. The induction of antigen-specific immunological tolerance to block undesired immune responses to self- or allogeneic antigens, while maintaining the integrity of the remaining immune system, has the potential to transform the current treatment of autoimmune disease and serve as a key enabling technology for therapies based on cell transplantation. PMID:26928211

  15. Aptamer Oligonucleotides: Novel Potential Therapeutic Agents in Autoimmune Disease.

    PubMed

    Li, Weibin; Lan, Xiaopeng

    2015-08-01

    Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid oligonucleotides generated in vitro based on affinity for certain target molecules by a process known as Systematic Evolution of Ligands by Exponential Enrichment. Aptamers can bind their target molecules with high specificity and selectivity by means of structure compatibility, stacking of aromatic rings, electrostatic and van der Waals interactions, and hydrogen bonding. With several advantages over monoclonal antibodies and other conventional small-molecule therapeutics, such as high specificity and affinity, negligible batch to batch variation, flexible modification and stability, lack of toxicity and low immunogenicity, aptamers are becoming promising novel diagnostic and therapeutic agents. This review focuses on the development of aptamers as potential therapeutics for autoimmune diseases, including diabetes mellitus, multiple sclerosis, rheumatoid arthritis, myasthenia gravis, and systemic lupus erythematosus. PMID:25993618

  16. Pathologically confirmed autoimmune encephalitis in suspected Creutzfeldt-Jakob disease

    PubMed Central

    Maat, Peter; de Beukelaar, Janet W.; Jansen, Casper; Schuur, Maaike; van Duijn, Cornelia M.; van Coevorden, Marleen H.; de Graaff, Esther; Titulaer, Maarten; Rozemuller, Annemieke J.

    2015-01-01

    Objective: To determine the clinical features and presence in CSF of antineuronal antibodies in patients with pathologically proven autoimmune encephalitis derived from a cohort of patients with suspected Creutzfeldt-Jakob disease (CJD). Methods: The Dutch Surveillance Centre for Prion Diseases performed 384 autopsies on patients with suspected CJD over a 14-year period (1998–2011). Clinical information was collected from treating physicians. Antineuronal antibodies were tested in CSF obtained postmortem by immunohistochemistry on fresh frozen rat brain sections, by Luminex assay for the presence of well-characterized onconeural antibodies, and by cell-based assays for antibodies against NMDAR, GABABR1/2, GABAAR GLUR1/2, LGI1, Caspr2, and DPPX. Results: In 203 patients, a diagnosis of definite CJD was made, while in 181 a variety of other conditions were diagnosed, mainly neurodegenerative. In 22 of these 181, the neuropathologist diagnosed autoimmune encephalitis. One patient was excluded because of lack of clinical information. Inflammatory infiltrates were predominantly perivascular and consisted mainly of T cells. The predominant locations were basal ganglia and thalamus (90%) and temporal lobes and hippocampus (81%). In 6 patients (29%), antineuronal antibodies were detected in postmortem CSF, directed against Hu, NMDAR, GABABR1/2, Caspr2, and an unidentified synaptic antigen in 2. The most frequent symptoms were dementia (90%), gait disturbance (86%), cerebellar signs (67%), and neuropsychiatric symptoms (67%). Immunopathologic and clinical findings did not differ between autoantibody-negative patients and patients with antineuronal antibodies. Conclusions: It is important to consider immune-mediated disorders in the differential diagnosis of rapidly progressive neurologic deficits. PMID:26601117

  17. IVIG in autoimmune disease - Potential next generation biologics.

    PubMed

    Zuercher, Adrian W; Spirig, Rolf; Baz Morelli, Adriana; Käsermann, Fabian

    2016-08-01

    Polyclonal plasma-derived IgG is a mainstay therapeutic of immunodeficiency disorders as well as of various inflammatory autoimmune diseases. In immunodeficiency the primary function of IVIG/SCIG is to replace missing antibody specificities, consequently a diverse Fab-based repertoire is critical for efficacy. Attempts to capture the Ig repertoire and express it as a recombinant IVIG product are currently ongoing. Likewise correction of the defective genes by gene therapy has also been tried. However, both approaches are far from becoming mainstream treatments. In contrast, some of the most important effector mechanisms relevant in therapy of autoimmunity are based on the Fc-portion of IgG; they include scavenging of complement and blockade/modulation of IgG receptors (Fc gamma receptor [FcγR] or the neonatal Fc receptor [FcRn]). These effects might be achieved with appropriately formulated Fc-fragments instead of full-length IgG, as suggested by a pilot study with monomeric plasma-derived Fc in children with ITP and in Kawasaki disease in the 1990s. Since then it has been proposed that structured multimerization of Fc fragments might confer efficacy at much lower doses than with IVIG. Accordingly, various molecular strategies are currently being explored to achieve controlled Fc multimerization, e.g. by fusion of IgG1 Fc to the IgG2 hinge-region or to the IgM tail-piece. Safety considerations will be crucial in the evaluation of these new entities. In a different approach, mutant Fc fragments and monoclonal antibodies have been designed for blockade of the FcRn.

  18. Non-alcoholic fatty liver disease.

    PubMed

    Pearce, Lynne

    2016-08-24

    Essential facts Non-alcoholic fatty liver disease (NAFLD) is an excess of fat in the liver that is not the result of excessive alcohol consumption or other secondary causes, such as hepatitis C. According to the National Institute for Health and Care Excellence, fatty liver - steatosis - affects between 20% and 30% of the population and its prevalence is increasing. PMID:27641564

  19. Cardiac autoimmunity in HIV related heart muscle disease

    PubMed Central

    Currie, P; Goldman, J; Caforio, A; Jacob, A; Baig, M; Brettle, R; Haven, A; Boon, N; McKenna, W

    1998-01-01

    Objective—To assess the frequency of circulating cardiac specific autoantibodies in HIV positive patients with and without echocardiographic evidence of left ventricular dysfunction.
Subjects—74 HIV positive patients including 28 with echocardiographic evidence of heart muscle disease, 52 HIV negative people at low risk of HIV infection, and 14 HIV negative drug users who had all undergone non-invasive cardiac assessment were studied along with a group of 200 healthy blood donors.
Results—Cardiac autoantibodies detected by indirect immunofluorescence (serum dilution 1/10) were more common in the HIV positive patients (15%), particularly the HIV heart muscle disease group (21%), than in HIV negative controls (3.5%) (both p < 0.001). By ELISA (dilution 1/320), abnormal anti-α myosin autoantibody concentrations were found more often in HIV patients with heart muscle disease (43%) than in HIV positive patients with normal hearts (19%) or in HIV negative controls (3%) (p < 0.05 and p < 0.001, respectively). Anti-α myosin autoantibody concentrations were greater in HIV positive patients than in HIV negative controls, regardless of cardiac status ((mean SD) 0.253 (0.155) v 0.170 (0.076); p = 0.003). In particular the mean antibody concentration was higher in the HIV heart muscle disease patients (0.291 (0.160) v 0.170 (0.076); p = 0.001) than in HIV negative controls. On follow up, six subjects with normal echocardiograms but raised autoantibody concentrations had died after a median of 298 days, three with left ventricular abnormalities at necropsy. This compared with a median survival of 536 days for 21 HIV positive patients with normal cardiological and immunological results.
Conclusions—There is an increased frequency of circulating cardiac specific autoantibodies in HIV positive individuals, particularly those with heart muscle disease. The data support a role for cardiac autoimmunity in the pathogenesis of HIV related heart

  20. Risk of cancer of unknown primary after hospitalization for autoimmune diseases.

    PubMed

    Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2015-12-15

    Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect.

  1. Risk of cancer of unknown primary after hospitalization for autoimmune diseases.

    PubMed

    Hemminki, Kari; Sundquist, Kristina; Sundquist, Jan; Ji, Jianguang

    2015-12-15

    Cancer of unknown primary (CUP) is a heterogeneous syndrome diagnosed at metastatic sites. The etiology is unknown but immune dysfunction may be a contributing factor. Patients with autoimmune diseases were identified from the Swedish Hospital Discharge Register and linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for subsequent CUP and compared with subjects without autoimmune diseases. A total of 789,681 patients were hospitalized for any of 32 autoimmune diseases during years 1964-2012; 2,658 developed subsequent CUP, giving an overall SIR of 1.27. A total of 16 autoimmune diseases were associated with an increased risk for CUP; polymyositis/dermatomyositis showed the highest SIR of 3.51, followed by primary biliary cirrhosis (1.81) and Addison's disease (1.77). CUP risk is known to be reduced in long-time users of pain-relieving nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin. For patients with ankylosing spondylitis and with some other autoimmune diseases, with assumed chronic medication by NSAIDSs, CUP risks decreased in long-term follow-up. The overall risk of CUP was increased among patients diagnosed with autoimmune diseases, which call for clinical attention and suggest a possible role of immune dysfunction in CUP. The associations with many autoimmune diseases were weak which may imply that autoimmunity may not synergize with CUP-related immune dysfunction. However, long-term NSAID medication probably helped to curtail risks in some autoimmune diseases and CUP risks were generally higher in autoimmune diseases for which NSAIDs are not used and for these CUP appears to be a serious side effect. PMID:26103152

  2. Are human endogenous retroviruses triggers of autoimmune diseases? Unveiling associations of three diseases and viral loci.

    PubMed

    Nexø, Bjørn A; Villesen, Palle; Nissen, Kari K; Lindegaard, Hanne M; Rossing, Peter; Petersen, Thor; Tarnow, Lise; Hansen, Bettina; Lorenzen, Tove; Hørslev-Petersen, Kim; Jensen, Sara B; Bahrami, Shervin; Lajer, Maria; Schmidt, Kathrine L M; Parving, Hans-Henrik; Junker, Peter; Laska, Magdalena J

    2016-02-01

    Autoimmune diseases encompass a plethora of conditions in which the immune system attacks its own tissue, identifying them as foreign. Multiple factors are thought to contribute to the development of immune response to self, including differences in genotypes, hormonal milieu, and environmental factors. Viruses including human endogenous retroviruses have long been linked to the occurrence of autoimmunity, but never proven to be causative factors. Endogenous viruses are retroviral sequences embedded in the host germline DNA and transmitted vertically through successive generations in a Mendelian manner. In this study by means of genetic epidemiology, we have searched for the involvement of endogenous retroviruses in three selected autoimmune diseases: multiple sclerosis, type 1 diabetes mellitus, and rheumatoid arthritis. We found that at least one human endogenous retroviral locus was associated with each of the three diseases. Although there was a significant overlap, most loci only occurred in one of the studied disease. Remarkably, within each disease, there was a statistical interaction (synergy) between two loci. Additional synergy between retroviral loci and human lymphocyte antigens is reported for multiple sclerosis. We speculate the possibility that recombinants or mixed viral particles are formed and that the resulting viruses stimulate the innate immune system, thereby initiating the autoimmune response. PMID:26091722

  3. In healthy primates, circulating autoreactive T cells mediate autoimmune disease.

    PubMed Central

    Genain, C P; Lee-Parritz, D; Nguyen, M H; Massacesi, L; Joshi, N; Ferrante, R; Hoffman, K; Moseley, M; Letvin, N L; Hauser, S L

    1994-01-01

    A T cell response against myelin basic protein (MBP) is thought to contribute to the central nervous system (CNS) inflammation that occurs in the human demyelinating disease multiple sclerosis. To test whether MBP-reactive T cells that are normally retrieved from the circulation are capable of inducing CNS disease, MBP-reactive T cell clones were isolated from the peripheral blood of healthy, unimmunized Callithrix jacchus (C. jacchus) marmosets. This primate species is characterized by a natural chimerism of bone marrow elements between siblings that should make possible adoptive transfer of MBP-reactive T cells. We report that MBP-reactive T cell clones efficiently and reproducibly transfer CNS inflammatory disease between members of C. jacchus chimeric sets. The demyelination that is characteristic of experimental allergic encephalomyelitis induced in C. jacchus by immunization against human white matter did not occur after adoptive transfer of the MBP-reactive clones. It was noteworthy that encephalitogenic T cell clones were diverse in terms of their recognition of different epitopes of MBP, distinguishing the response in C. jacchus from that in some inbred rodents in which restricted recognition of MBP occurs. These findings are the first direct evidence that natural populations of circulating T cells directed against a CNS antigen can mediate an inflammatory autoimmune disease. Images PMID:7521889

  4. Stem cell transplantation and mesenchymal cells to treat autoimmune diseases.

    PubMed

    Tyndall, Alan; van Laar, Jacob M

    2016-06-01

    Since the start of the international stem cell transplantation project in 1997, over 2000 patients have received a haematopoietic stem cell transplant (HSCT), mostly autologous, as treatment for a severe autoimmune disease, the majority being multiple sclerosis (MS), systemic sclerosis (SSc) and Crohn's disease. There was an overall 85% 5-year survival and 43% progression-free survival. Around 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many cases, e.g. systemic sclerosis, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented, beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of the three running large prospective randomized controlled trials will allow modification of the protocols to reduce the high transplant-related mortality which relates to regimen intensity, age of patient, and comorbidity. Mesenchymal stromal cells (MSC), often incorrectly called stem cells, have been the intense focus of in vitro studies and animal models of rheumatic and other diseases over more than a decade. Despite multiple plausible mechanisms of action and a plethora of positive in vivo animal studies, few randomised controlled clinical trials have demonstrated meaningful clinical benefit in any condition so far. This could be due to confusion in cell product terminology, complexity of clinical study design and execution or agreement on meaningful outcome measures. Within the rheumatic diseases, SLE and rheumatoid arthritis (RA) have received most attention. Uncontrolled multiple trial data from over 300 SLE patients have been published from one centre suggesting a positive outcome; one single centre comparative study in 172 RA was positive. In addition, small numbers of patients with Crohn's disease, multiple sclerosis, primary Sjögren's disease, polymyositis/dermatomyositis and type II diabetes

  5. Cell and tissue engineering for liver disease.

    PubMed

    Bhatia, Sangeeta N; Underhill, Gregory H; Zaret, Kenneth S; Fox, Ira J

    2014-07-16

    Despite the tremendous hurdles presented by the complexity of the liver's structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near- and long-term prospects for such cell-based therapies and the unique challenges for clinical translation.

  6. Scientists find link between allergic and autoimmune diseases in mouse study

    Cancer.gov

    Scientists at the National Institutes of Health, and their colleagues, have discovered that a gene called BACH2 may play a central role in the development of diverse allergic and autoimmune diseases, such as multiple sclerosis, asthma, Crohn's disease, ce

  7. Immune thrombocytopenia and autoimmune thyroid disease: a controversial overlap

    PubMed Central

    de Campos, Fernando Peixoto Ferraz

    2015-01-01

    Immune thrombocytopenia (ITP) is an entity characterized by a platelet count of less than 100 × 109/L in the absence of other causes of thrombocytopenia, such as viral infections, rheumatic diseases, or drugs. Grave’s disease is also an autoimmune condition in which thrombocytopenia is often observed. Moreover, in the literature, many reports show a marked interference of the thyroid dysfunction (mainly hyperthyroidism) in the control of thrombocytopenia. Although this issue still remains debatable, the authors report the case of a young woman with a previous diagnosis of ITP with a brilliant initial response to corticotherapy. Some years after this diagnosis, the patient presented thyrotoxicosis due to Grave’s disease and the thrombocytopenia relapsed, but this time there was no response to the glucocorticoids. Only after the radioiodine I-131 thyroid ablation the control of thrombocytopenia was achieved. The authors call attention to this overlap and for testing thyroid function in every patient with an unexpected negative response to corticotherapy. PMID:26484334

  8. Thyroid peroxidase and the induction of autoimmune thyroid disease.

    PubMed Central

    McLachlan, S M; Atherton, M C; Nakajima, Y; Napier, J; Jordan, R K; Clark, F; Rees Smith, B

    1990-01-01

    Animal models of autoimmune thyroid disease are associated with thyroglobulin (Tg) as autoantigen whereas in man the autoimmune response to microsomal antigen/thyroid peroxidase (TPO) appears to play a major role in thyroiditis. Consequently, we have compared the ability of TPO and Tg to induce thyroid autoantibodies and thyroid damage in mice known to be susceptible (CBA/J) or resistant (BALB/c) to thyroiditis induced using murine Tg. Groups of three to five mice were immunized twice using Freund's complete adjuvant with 80-100 micrograms highly purified porcine (p) TPO, pTg, rat (r) Tg, human Tg, bovine serum albumin (BSA) or BSA + 0.2 micrograms pTg (the level of Tg contamination of TPO). Four weeks after immunization with TPO, plasma from CBA/J (but not BALB/c) mice contained IgG class antibodies which bound to TPO-coated tubes in the presence or absence of excess Tg (and could therefore be clearly distinguished from Tg antibodies) but there was no evidence of thyroiditis in either strain of mice. In contrast, in CBA/J mice immunized with rTg and, to a lesser extent in mice that had received pTg, thyroid tissue was infiltrated with lymphoid cells and/or neutrophils and antibodies to pTg (but not pTPO) were present. Our observations demonstrate that induction of TPO antibody alone is insufficient to lead to thyroiditis in CBA/J mice. Further, these studies emphasize the complex interactions between MHC and different thyroid antigens in the processes leading to thyroid destruction. PMID:2311297

  9. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

    PubMed

    Deng, Yaxiong; Huang, Xin; Wu, Haijing; Zhao, Ming; Lu, Qianjin; Israeli, Eitan; Dahan, Shani; Blank, Miri; Shoenfeld, Yehuda

    2016-05-01

    Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches. PMID:26812350

  10. Some like it hot: The emerging role of spicy food (capsaicin) in autoimmune diseases.

    PubMed

    Deng, Yaxiong; Huang, Xin; Wu, Haijing; Zhao, Ming; Lu, Qianjin; Israeli, Eitan; Dahan, Shani; Blank, Miri; Shoenfeld, Yehuda

    2016-05-01

    Autoimmune diseases refer to a spectrum of diseases characterized by an active immune response against the host, which frequently involves increased autoantibody production. The pathogenesis of autoimmune diseases is multifactorial and the exploitation of novel effective treatment is urgent. Capsaicin is a nutritional factor, the active component of chili peppers, which is responsible for the pungent component of chili pepper. As a stimuli, capsaicin selectively activate transient receptor potential vanilloid subfamily 1(TRPV1) and exert various biological effects. This review discusses the effect of capsaicin through its receptor on the development and modulation of autoimmune diseases, which may shed light upon potential therapies in capsaicin-targeted approaches.

  11. Interaction between periodontitis and liver diseases

    PubMed Central

    Han, Pengyu; Sun, Dianxing; Yang, Jie

    2016-01-01

    Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

  12. [The diagnostic value of immunologic findings in the differentiation of chronic liver diseases].

    PubMed

    Manns, M; Meyer zum Büschenfelde, K H; Arnold, W

    1988-12-01

    Various types of virus induced and non-virus induced chronic active hepatitis (CAH) as well as chronic non-suppurative destructive cholangitis (PBC) and primary sclerosing cholangitis have to be distinguished. Classical autoimmune type "lupoid" CAH is characterized by antinuclear antibodies (ANA), liver membrane antibodies (LMA) and smooth muscle antibodies (SMA). A second subgroup of autoimmune type CAH is characterized by anti liver kidney-microsomal antibodies (LKM) which are directed against a specific cytochrome p-450 isoenzyme. A third subgroup of autoimmune type CAH is identified by auto-antibodies to a soluble cytoplasmic liver antigen (SLA). Autoimmune type CAH profits from immuno-suppressive therapy, i.e. corticosteroids alone or in combination with azathioprin. Chronic hepatitis B virus infection is nowadays treated with Interferon when HBV-DNA is detectable in serum, duration of liver disease is less than 5 years and superinfection with HDV and HIV can be excluded. PBC is diagnosed through the detection of antimitochondrial antibodies (AMA) and its PBC specific subtypes anti p 62 (M2) and anti p 48. Aetiology and pathogenesis of PBC are still unknown. Liver transplantation is an established therapy for endstage PBC. This is also true for primary sclerosing cholangitis (PSC).

  13. Autoimmune pancreatitis: a systemic immune complex mediated disease.

    PubMed

    Deshpande, Vikram; Chicano, Sonia; Chiocca, Sonia; Finkelberg, Dmitry; Selig, Martin K; Mino-Kenudson, Mari; Brugge, William R; Colvin, Robert B; Lauwers, Gregory Y

    2006-12-01

    Autoimmune pancreatitis (AIP) is a mass forming inflammatory pancreatobiliary-centric disease. Recent reports of multiorgan inflammatory mass forming lesions with increased numbers of IgG4 positive plasma cells suggest that AIP may have a systemic component. In this study, we explore the systemic nature of AIP, investigate the relevance of subtyping AIP, perform a systematic study of tissue IgG4 immunoperoxidase, and ultrastructurally evaluate the presence of immune complexes. Our study group consisted of 36 patients with AIP, 21 of whom underwent a Whipple procedure. On the basis of the pattern of inflammation, pancreatic involvement was subtyped as ductocentric (AIP-D) or lobulocentric (AIP-L). Extrapancreatic lesions included bile duct (n=3), salivary glands (n=3), lung (n=2), gallbladder (n=11), and kidney (n=4). Clinical and radiologic data was recorded. Immunohistochemistry for IgG4 was performed on both pancreatic and extrapancreatic tissues and the numbers of IgG4 positive plasma cells were semiquantitatively scored. A control cohort composed of pancreatic adenocarcinoma (n=19) and chronic pancreatitis-not otherwise specified (NOS) (n=14) was also evaluated. Eleven pancreatic specimens, including 2 cases of chronic pancreatitis-NOS and 4 kidneys were evaluated ultrastructurally. The pancreas, bile duct, gall bladder, salivary gland, kidney, and lung lesions were characterized by dense lymphoplasmacytic infiltrates with reactive fibroblasts and venulitis. IgG4 positive plasma cells were identified in all pancreatic and extrapancreatic lesions. The AIP cases showed significantly more pancreatic IgG4 positive plasma cells than chronic pancreatitis-NOS or adenocarcinoma (P=0.001). However, IgG4 positive cells were identified in 57.1% of chronic pancreatitis-NOS and 47.4% of ductal adenocarcinoma. Fifteen of 21 resected cases were classified as AIP-D, and 6 as AIP-L, the latter notably showing significantly more IgG4 positive plasma cells than the former (P=0

  14. Emerging Role and Therapeutic Implication of Wnt Signaling Pathways in Autoimmune Diseases

    PubMed Central

    Shi, Juan; Chi, Shuhong; Xue, Jing; Yang, Jiali; Li, Feng; Liu, Xiaoming

    2016-01-01

    The Wnt signaling pathway plays a key role in many biological aspects, such as cellular proliferation, tissue regeneration, embryonic development, and other systemic effects. Under a physiological condition, it is tightly controlled at different layers and arrays, and a dysregulated activation of this signaling has been implicated into the pathogenesis of various human disorders, including autoimmune diseases. Despite the fact that therapeutic interventions are available for ameliorating disease manifestations, there is no curative therapy currently available for autoimmune disorders. Increasing lines of evidence have suggested a crucial role of Wnt signaling during the pathogenesis of many autoimmune diseases; in addition, some of microRNAs (miRNAs), a class of small, noncoding RNA molecules capable of transcriptionally regulating gene expression, have also recently been demonstrated to possess both physiological and pathological roles in autoimmune diseases by regulating the Wnt signaling pathway. This review summarizes currently our understanding of the pathogenic roles of Wnt signaling in several major autoimmune disorders and miRNAs, those targeting Wnt signaling in autoimmune diseases, with a focus on the implication of the Wnt signaling as potential biomarkers and therapeutic targets in immune diseases, as well as miRNA-mediated regulation of Wnt signaling activation in the development of autoimmune diseases. PMID:27110577

  15. The role of genetic factors in autoimmune disease: implications for environmental research.

    PubMed Central

    Cooper, G S; Miller, F W; Pandey, J P

    1999-01-01

    Studies in both humans and in animal models of specific disorders suggest that polymorphisms of multiple genes are involved in conferring either a predisposition to or protection from autoimmune diseases. Genes encoding polymorphic proteins that regulate immune responses or the rates and extent of metabolism of certain chemical structures have been the focus of much of the research regarding genetic susceptibility. We examine the type and strength of evidence concerning genetic factors and disease etiology, drawing examples from a number of autoimmune diseases. Twin studies of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type I diabetes, and multiple sclerosis (MS) indicate that disease concordance in monozygotic twins is 4 or more times higher than in dizygotic twins. Strong familial associations (odds ratio ranging from 5-10) are seen in studies of MS, type I diabetes, Graves disease, discoid lupus, and SLE. Familial association studies have also reported an increased risk of several systemic autoimmune diseases among relatives of patients with a systemic autoimmune disease. This association may reflect a common etiologic pathway with shared genetic or environmental influences among these diseases. Recent genomewide searches in RA, SLE, and MS provide evidence for multiple susceptibility genes involving major histocompatibility complex (MHC) and non-MHC loci; there is also evidence that many autoimmune diseases share a common set of susceptibility genes. The multifactorial nature of the genetic risk factors and the low penetrance of disease underscore the potential influence of environmental factors and gene-environment interactions on the etiology of autoimmune diseases. PMID:10502533

  16. Characterization of intermediate T-cell receptor cells expanding in the liver, thymus and other organs in autoimmune lpr mice: parallel analysis with their normal counterparts.

    PubMed Central

    Iiai, T; Kimura, M; Kawachi, Y; Hirokawa, K; Watanabe, H; Hatakeyama, K; Abo, T

    1995-01-01

    Autoimmune MRL-lpr/lpr (lpr) mice were previously demonstrated to have an abnormal proliferation of intermediate T-cell receptor (TCR) cells of extrathymic origin in the liver. Despite this situation, thymectomy in lpr mice resulted in amelioration of autoimmune disease. To understand the underlying mechanism, we investigated associated T-cell differentiation in the thymus and other organs of these mice. When the disease was evoked, T cells with extrathymic properties, i.e. intermediate TCR-alpha beta cells expressing double-negative (DN) CD4-8- phenotype and interleukin-2 (IL-2) receptor beta-chain, became prominent not only in the liver, but also in the thymus. Such thymic T cells mainly resided in the medulla. A small-scale localization of such T cells was seen in the thymic medulla even in normal control mice. There was a heterogeneity among intermediate TCR cells in terms of the composition of DN cells and the expression of CD2 and B220 antigens, depending on the organs and the sites in the same organ. Intermediate TCR cells in the liver, thymus and autoimmune target organs (e.g. kidney) contained a high proportion of the active form (CD2+B220-), while intermediate TCR cells accumulating in peripheral organs, the spleen and lymph nodes, were mainly of the inactive form (CD2-B220+). The active form had an ability to proliferate in response to IL-2 and SEB, whereas the inactive form did not. The present results suggest that the proliferation of intermediate TCR cells occur at multiple sites; this may explain the effect of thymectomy, namely, the retarded onset of disease, in lpr mice. Images Figure 3 PMID:7790034

  17. Autologous Peripheral Blood Stem Cell Transplantation in Patients With Life Threatening Autoimmune Diseases

    ClinicalTrials.gov

    2005-06-23

    Purpura, Schoenlein-Henoch; Graft Versus Host Disease; Anemia, Hemolytic, Autoimmune; Rheumatoid Arthritis; Churg-Strauss Syndrome; Hypersensitivity Vasculitis; Wegener's Granulomatosis; Systemic Lupus Erythematosus; Giant Cell Arteritis; Pure Red Cell Aplasia; Juvenile Rheumatoid Arthritis; Polyarteritis Nodosa; Autoimmune Thrombocytopenic Purpura; Takayasu Arteritis

  18. [Diagnosis of liver diseases by classification of laboratory signal factor pattern findings with the Mahalanobis·Taguchi Adjoint method].

    PubMed

    Nakajima, Hisato; Yano, Kouya; Uetake, Shinichirou; Takagi, Ichiro

    2012-02-01

    There are many autoimmune liver diseases in which diagnosis is difficult so that overlap is accepted, and this negatively affects treatment. The initial diagnosis is therefore important for later treatment and convalescence. We distinguished autoimmune cholangitis, autoimmune hepatitis and primary biliary cirrhosis by the Mahalanobis·Taguchi Adjoint (MTA) method in the Mahalanobis·Taguchi system and analyzed the pattern of factor effects by the MTA method. As a result, the characteristic factor effect pattern of each disease was classified, enabling the qualitative evaluation of cases including overlapping cases which were difficult to diagnose.

  19. Metabolic therapy: lessons from liver diseases.

    PubMed

    Garcia-Ruiz, Carmen; Marí, Montserrat; Colell, Anna; Morales, Albert; Fernandez-Checa, Jose C

    2011-12-01

    Fatty liver disease is one of most prevalent metabolic liver diseases, which includes alcoholic (ASH) and nonalcoholic steatohepatitis (NASH). Its initial stage is characterized by fat accumulation in the liver, that can progress to steatohepatitis, a stage of the disease in which steatosis is accompanied by inflammation, hepatocellular death, oxidative stress and fibrosis. Recent evidence in experimental models as well as in patients with steatohepatitis have uncovered a role for cholesterol and sphingolipids, particularly ceramide, in the transition from steatosis to steatohepatitis, insulin resistance and hence disease progression. Cholesterol accumulation and its trafficking to mitochondria sensitizes fatty liver to subsequent hits including inflammatory cytokines, such as TNF/Fas, in a pathway involving ceramide generation by acidic sphingomyelinase (ASMase). Thus, targeting both cholesterol and/or ASMase may represent a novel therapeutic approach of relevance in ASH and NASH, two of the most common forms of liver diseases worldwide. PMID:21933146

  20. Management of coagulation abnormalities in liver disease.

    PubMed

    Potze, Wilma; Porte, Robert J; Lisman, Ton

    2015-01-01

    Liver disease is characterized by changes in all phases of hemostasis. These hemostatic alterations were long considered to predispose patients with liver disease towards a bleeding tendency, as they are associated with prolonged conventional coagulation tests. However, these patients may also suffer from thrombotic complications, and we now know that the hemostatic system in patient with liver disease is, in fact, in a rebalanced state. In this review we discuss the concept of rebalanced hemostasis and its implications for clinical management of patients with liver disease. For instance, there is no evidence that the use of prophylactic blood product transfusion prior to invasive procedures reduces bleeding risk. Clinicians should also be aware of the possibility of thrombosis occurring in patients with a liver disease, and regular thrombosis prophylaxis should not be withheld in these patients.

  1. [AUTOIMMUNE REACTIONS IN PATIENTS WITH DISEASES OF A THYROID GLAND].

    PubMed

    Saidova, F Kh; Shakhsuvarov, O M; Guseynov, R G; Akhmedova, L M; Aslanova, Zh B

    2015-11-01

    A state of autoimmunity was studied in 25 patients, suffering diffuse toxic goiter (DTG), and in 20--in nodular euthyroid goiter (NEG) before and after the operation. The level of circulating immune complexes, quantity of cytotoxic lymphocytes, the subpopulation index, the apoptosis marker were determined. There was established, that in NEG autoimmune disorders have occurred rarer and were less severe, than in DTG.

  2. Mesenchymal Stem Cell Therapy for Autoimmune Disease: Risks and Rewards.

    PubMed

    Munir, Hafsa; McGettrick, Helen M

    2015-09-15

    Mesenchymal stem cells (MSC) possess a range of immunomodulatory properties which they exert through soluble mediators and through direct cell-cell contact. Due to these immune regulatory properties, the safety and clinical efficacy of MSC treatment has been tested in a number of autoimmune disorders. In this review we analyze the current data from early phase trials into Crohn's disease, systemic lupus erythematosus, and rheumatoid arthritis. In general, no adverse side effects were observed in patients treated with MSC; however, their clinical efficacy is difficult to interpret. Systemic or site-specific administration of MSC has been reported to exert potent immunomodulatory effects in 7 of the 11 trials discussed. Nonetheless, the mechanism(s) by which MSC exert their regulatory effects in vivo remain largely unknown. We discuss potential limitations or safety concerns associated with MSC therapy, including the heterogeneity of MSC and their potential contribution to disease pathogenesis, which need to be considered when designing future clinical trials, along with the need to standardize trial design. Although we are bridging the translational gap between scientific observations on MSC function and clinical applications for therapy, our understanding of basic MSC biology is still limited. Despite these issues, large, double-blinded, multicenter clinical trials are already underway. Further research into the endogenous function of MSC is required to elucidate the mechanism by which therapeutic MSC are acting.

  3. Current Status in the Therapy of Liver Diseases

    PubMed Central

    Uhl, Philipp; Fricker, Gert; Haberkorn, Uwe; Mier, Walter

    2014-01-01

    Hepatic diseases, like viral hepatitis, autoimmune hepatitis, hereditary hemochromatosis, non-alcoholic fatty liver disease (NAFLD) and Wilson’s disease, play an important role in the development of liver cirrhosis and, hence, hepatocellular carcinoma. In this review, the current treatment options and the molecular mechanisms of action of the drugs are summarized. Unfortunately, the treatment options for most of these hepatic diseases are limited. Since hepatitis B (HBV) and C (HCV) infections are the most common causes of liver cirrhosis and hepatocellular carcinoma, they are the focus of the development of new drugs. The current treatment of choice for HBV/HCV infection is an interferon-based combination therapy with oral antiviral drugs, like nucleos(t)ide analogues, which is associated with improving the therapeutic success and also preventing the development of resistances. Currently, two new protease inhibitors for HCV treatment are expected (deleobuvir, faldaprevir) and together with the promising drug, daclatasvir (NS5A-inhibitor, currently in clinical trials), adequate therapy is to be expected in due course (circumventing the requirement of interferon with its side-effects), while in contrast, efficient HBV therapeutics are still lacking. In this respect, entry inhibitors, like Myrcludex B, the lead substance of the first entry inhibitor for HBV/HDV (hepatitis D) infection, provide immense potential. The pharmacokinetics and the mechanism of action of Myrcludex B are described in detail. PMID:24786290

  4. Current status in the therapy of liver diseases.

    PubMed

    Uhl, Philipp; Fricker, Gert; Haberkorn, Uwe; Mier, Walter

    2014-01-01

    Hepatic diseases, like viral hepatitis, autoimmune hepatitis, hereditary hemochromatosis, non-alcoholic fatty liver disease (NAFLD) and Wilson's disease, play an important role in the development of liver cirrhosis and, hence, hepatocellular carcinoma. In this review, the current treatment options and the molecular mechanisms of action of the drugs are summarized. Unfortunately, the treatment options for most of these hepatic diseases are limited. Since hepatitis B (HBV) and C (HCV) infections are the most common causes of liver cirrhosis and hepatocellular carcinoma, they are the focus of the development of new drugs. The current treatment of choice for HBV/HCV infection is an interferon-based combination therapy with oral antiviral drugs, like nucleos(t)ide analogues, which is associated with improving the therapeutic success and also preventing the development of resistances. Currently, two new protease inhibitors for HCV treatment are expected (deleobuvir, faldaprevir) and together with the promising drug, daclatasvir (NS5A-inhibitor, currently in clinical trials), adequate therapy is to be expected in due course (circumventing the requirement of interferon with its side-effects), while in contrast, efficient HBV therapeutics are still lacking. In this respect, entry inhibitors, like Myrcludex B, the lead substance of the first entry inhibitor for HBV/HDV (hepatitis D) infection, provide immense potential. The pharmacokinetics and the mechanism of action of Myrcludex B are described in detail.

  5. Genetics of autoimmune diseases: insights from population genetics.

    PubMed

    Ramos, Paula S; Shedlock, Andrew M; Langefeld, Carl D

    2015-11-01

    Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function genes are enriched for signals of positive selection, it is thought that the prevalence of AD risk alleles seen in different population is partially the result of differing selective pressures (for example, due to pathogens). With the advent of high-throughput technologies, new analytical methodologies and large-scale projects, evidence for the role of natural selection in contributing to the heritable component of ADs keeps growing. This review summarizes the genetic regions associated with susceptibility to different ADs and concomitant evidence for selection, including known agents of selection exerting selective pressure in these regions. Examples of specific adaptive variants with phenotypic effects are included as an evidence of natural selection increasing AD susceptibility. Many of the complexities of gene effects in different ADs can be explained by population genetics phenomena. Integrating AD susceptibility studies with population genetics to investigate how natural selection has contributed to genetic variation that influences disease risk will help to identify functional variants and elucidate biological mechanisms. As such, the study of population genetics in human population holds untapped potential for elucidating the genetic causes of human disease and more rapidly focusing to personalized medicine.

  6. Genetics of autoimmune diseases: insights from population genetics

    PubMed Central

    Ramos, Paula S; Shedlock, Andrew M; Langefeld, Carl D

    2015-01-01

    Human genetic diversity is the result of population genetic forces. This genetic variation influences disease risk and contributes to health disparities. Autoimmune diseases (ADs) are a family of complex heterogeneous disorders with similar underlying mechanisms characterized by immune responses against self. Collectively, ADs are common, exhibit gender and ethnic disparities, and increasing incidence. As natural selection is an important influence on human genetic variation, and immune function genes are enriched for signals of positive selection, it is thought that the prevalence of AD risk alleles seen in different population is partially the result of differing selective pressures (for example, due to pathogens). With the advent of high-throughput technologies, new analytical methodologies and large-scale projects, evidence for the role of natural selection in contributing to the heritable component of ADs keeps growing. This review summarizes the genetic regions associated with susceptibility to different ADs and concomitant evidence for selection, including known agents of selection exerting selective pressure in these regions. Examples of specific adaptive variants with phenotypic effects are included as an evidence of natural selection increasing AD susceptibility. Many of the complexities of gene effects in different ADs can be explained by population genetics phenomena. Integrating AD susceptibility studies with population genetics to investigate how natural selection has contributed to genetic variation that influences disease risk will help to identify functional variants and elucidate biological mechanisms. As such, the study of population genetics in human population holds untapped potential for elucidating the genetic causes of human disease and more rapidly focusing to personalized medicine. PMID:26223182

  7. Skin disease and thyroid autoimmunity in atopic South Italian children

    PubMed Central

    Pedullà, Marcella; Fierro, Vincenzo; Marzuillo, Pierluigi; Capuano, Francesco; Miraglia del Giudice, Emanuele; Ruocco, Eleonora

    2016-01-01

    AIM To verify the prevalence of thyroid autoimmunity (TA) and the possible association between atopy and TA in children affected by skin disease. METHODS Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up for atopy, the children were divided into two groups: Atopics and non-atopics. TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay. RESULTS In all children with skin disease, a significant prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P = 0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI: 1.71-19.35) were observed. These findings were confirmed as significant in children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P = 0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a significantly higher prevalence of TA (26.9%), but none of the non-atopics showed CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2) prevalence of TA, compared with none of the non-atopics. CONCLUSION In children with skin disease, atopy seems to be associated with an increased risk of TA.

  8. Skin disease and thyroid autoimmunity in atopic South Italian children

    PubMed Central

    Pedullà, Marcella; Fierro, Vincenzo; Marzuillo, Pierluigi; Capuano, Francesco; Miraglia del Giudice, Emanuele; Ruocco, Eleonora

    2016-01-01

    AIM To verify the prevalence of thyroid autoimmunity (TA) and the possible association between atopy and TA in children affected by skin disease. METHODS Three hundred and twenty-four children consecutively referred due to skin disease symptoms to our Pediatric Department were enrolled. One hundred and eighty-seven were diagnosed with atopic dermatitis (AD), 95 with acute urticaria, 40 with chronic urticaria (CU), and 2 with alopecia areata (AA). According to the work-up for atopy, the children were divided into two groups: Atopics and non-atopics. TA was diagnosed by serum thyroid peroxidase autoantibodies and/or thyroglobulin autoantibodies levels more than twice normal values over a period of two months by immunoassay. RESULTS In all children with skin disease, a significant prevalence of TA in atopics compared with non-atopics (13.67% vs 2.67%, P = 0.0016) and a significant association between TA and atopy (OR = 5.76, 95%CI: 1.71-19.35) were observed. These findings were confirmed as significant in children with AD: TA in atopics was 11.5%, while TA in non-atopics was 2.7% (P = 0.03, OR = 4.68, 95%CI: 1.02-21.38). In addition, atopics with CU showed a significantly higher prevalence of TA (26.9%), but none of the non-atopics showed CU (P = 0.0326). On the other hand, atopics with AA showed a 100% (2 out of 2) prevalence of TA, compared with none of the non-atopics. CONCLUSION In children with skin disease, atopy seems to be associated with an increased risk of TA. PMID:27610344

  9. Role of the intestinal microbiome in liver disease.

    PubMed

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Licona-Limon, Paula; Flavell, Richard A

    2013-10-01

    The liver integrates metabolic outcomes with nutrient intake while preventing harmful signals derived from the gut to spread throughout the body. Direct blood influx from the gastrointestinal tract through the portal vein makes the liver a critical firewall equipped with a broad array of immune cells and innate immune receptors that recognize microbial-derived products, microorganisms, toxins and food antigens that have breached the intestinal barrier. An overwhelming amount of evidence obtained in the last decade indicates that the intestinal microbiota is a key component of a wide variety of physiological processes, and alterations in the delicate balance that represents the intestinal bacterial communities are now considered important determinants of metabolic syndrome and immunopathologies. Moreover, it is now evident that the interaction between the innate immune system and the intestinal microbiota during obesity or autoimmunity promotes chronic liver disease progression and therefore it might lead to novel and individualized therapeutic approaches. In this review, we discuss a growing body of evidence that highlights the central relationship between the immune system, the microbiome, and chronic liver disease initiation and progression. PMID:24075647

  10. Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

    PubMed Central

    Saich, Rebecca; Chapman, Roger

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree. Symptoms include itch and lethargy and in advanced cases cholangitis and end-stage liver disease, however increasing numbers of asymptomatic individuals are being identified. The disease is rare in the general population but is strongly associated with inflammatory bowel disease (IBD) affecting up to 5% of patients with Ulcerative Colitis, with a slightly lower prevalence (up to 3.6%) in Crohn's disease. The strength of this association means that the vast majority (> 90%) of patients with PSC also have IBD, although many may have only mild gastro-intestinal symptoms. Usually IBD presents before PSC, although vice-versa can occur and the onset of both conditions can be separated in some cases by many years. Mean age of diagnosis of PSC is in the fifth decade of life with a strong male predominance. Risk is increased in those with a family history of PSC, suggesting a genetic predisposition and the disease is almost exclusive to non-smokers. The ulcerative colitis associated with PSC is characteristically mild, runs a quiescent course, is associated with rectal sparing, more severe right sided disease, backwash ileitis and has a high risk of pouchitis post-colectomy. Most worrisome is the high risk of colorectal malignancy which necessitates routine colonoscopic surveillance. Cholangiocarcinoma is also a frequent complication of PSC with a 10%-15% lifetime risk of developing this condition. Treatment with high dose ursodeoxycholic acid offers some chemoprotective effects against colorectal malignancy and may decrease symptoms, biochemical and histological progression of liver disease. Small duct PSC patients characteristically have normal cholangiography, and liver biopsy is required for diagnosis, it appears to have a more favourable prognosis. Autoimmune Hepatitis (AIH) is also more prevalent

  11. Coagulation factors in chronic liver disease.

    PubMed

    Donaldson, G W; Davies, S H; Darg, A; Richmond, J

    1969-03-01

    Coagulation studies were carried out on 30 patients with chronic liver disease. The clotting defect was complex and involved factors V, VII, IX (Christmas factor), and prothrombin. Some patients showed a significant depression of factor IX in the presence of a normal one-stage prothrombin time. Thrombotest was found to be a good indicator of factor IX deficiency in this group of patients and may be of use as an additional liver function test. The screening of patients with liver disease for surgery or liver biopsy should assess the coagulation factors involved in both intrinsic and extrinsic thromboplastin generation.

  12. Chronic Liver Disease and Asian Americans/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Asian Americans/Pacific Islanders Among Asian Americans, chronic liver disease is ... women. At a glance – Cancer Rates for Asian/Pacific Islanders (2008-2012) Cancer Incidence Rates per 100, ...

  13. Cytokine Gene Polymorphisms and Human Autoimmune Disease in the Era of Genome-Wide Association Studies

    PubMed Central

    2012-01-01

    Cytokine (receptor) genes have traditionally attracted great interest as plausible genetic risk factors for autoimmune disease. Since 2007, the implementation of genome-wide association studies has facilitated the robust identification of allelic variants in more than 35 cytokine loci as susceptibility factors for a wide variety of over 15 autoimmune disorders. In this review, we catalog the gene loci of interleukin, chemokine, and tumor necrosis factor receptor superfamily and ligands that have emerged as autoimmune risk factors. We examine recent progress made in the clarification of the functional mechanisms by which polymorphisms in the genes coding for interleukin-2 receptor alpha (IL2RA), IL7R, and IL23R may alter risk for autoimmune disease, and discuss opposite autoimmune risk alleles found, among others, at the IL10 locus. PMID:22191464

  14. Hypergammaglobulinemia in the pediatric population as a marker for underlying autoimmune disease: a retrospective cohort study

    PubMed Central

    2013-01-01

    Background The significance of hypergammaglobulinemia as a marker of immune activation is unknown, as a differential diagnosis for hypergammaglobulinemia in children has not been adequately established. The goal of this study was to identify conditions associated with hypergammaglobulinemia in children, with the hypothesis that elevated immunoglobulin levels may precede or predict the development of autoimmune conditions. Methods We reviewed the medical records for all children with IgG level ≥2000 mg/dL treated at a tertiary care children’s hospital from January 1, 2000 through December 31, 2009. We compared clinical and laboratory features of these patients, and developed an algorithm to predict the likelihood of underlying autoimmunity based on these characteristics. Results After excluding children who had received IVIG, a total of 442 patients with hypergammaglobulinemia were identified. Of these, nearly half had autoimmune conditions, most frequently systemic lupus erythematosus and lupus-related disorders. Autoimmune gastrointestinal disorders such as inflammatory bowel disease were also common. Infectious diseases were the next largest category of diseases, followed with much less frequency by malignant, drug-related, and other conditions. In comparison with non-autoimmune conditions, patients with autoimmune disease had higher IgG levels, lower white blood cell counts, lower hemoglobin values, and lower C-reactive protein (CRP) levels. Multivariable logistic regression confirmed that CRP (P = 0.002), white blood cell count (P < 0.001), hemoglobin (P = 0.015), and female gender (P < 0.001) are independent risk factors for autoimmune disease in patients with high IgG levels. Conclusions In a cohort of pediatric patients at a tertiary care children’s hospital, hypergammaglobulinemia was most commonly associated with autoimmune diseases. In female patients with hypergammaglobulinemia, the presence of leukopenia, anemia, and normal CRP

  15. New Insights into the Management of Patients with Autoimmune Diseases or Inflammatory Disorders During Pregnancy.

    PubMed

    Tavakolpour, Soheil; Rahimzadeh, Ghazal

    2016-09-01

    The treatment of autoimmune diseases remains a serious problem. Current therapies can lead to adverse effects in patients. One of the most vulnerable patient groups is pregnant women. It has been reported that different autoimmune diseases have a certain trend during pregnancy and after delivery which could be explained by maternal immune responses. Better management of pregnant women with autoimmune diseases or inflammatory disorders could be achieved by linking such alterations in immune responses and governed immune responses in different autoimmune disorders while considering various reports of autoimmune conditions during pregnancy. This study considers changing the T helper cells (Th1) and Th2 balance and suggests some new approaches for the better management of autoimmune diseases in pregnant women based on immune responses. Additionally, the possible role of Th17, alterations in some selected autoimmune diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), psoriasis, systemic lupus erythematosus (SLE), atopic dermatitis (AD), asthma and pemphigus during pregnancy, and possible associated mechanisms are discussed. PMID:27300757

  16. Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

    PubMed

    Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

    2014-01-01

    Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study.

  17. Same-sex marriage, autoimmune thyroid gland dysfunction and other autoimmune diseases in Denmark 1989-2008.

    PubMed

    Frisch, Morten; Nielsen, Nete Munk; Pedersen, Bo Vestergaard

    2014-01-01

    Autoimmune diseases have been little studied in gay men and lesbians. We followed 4.4 million Danes, including 9,615 same-sex married (SSM) persons, for 47 autoimmune diseases in the National Patient Registry between 1989 and 2008. Poisson regression analyses provided first hospitalization rate ratios (RRs) comparing rates between SSM individuals and persons in other marital status categories. SSM individuals experienced no unusual overall risk of autoimmune diseases. However, the risk of autoimmune thyroid dysfunction was increased, notably Hashimoto's thyroiditis (women(SSM), RR = 2.92; 95% confidence interval (CI) 1.74-4.55) and Graves' disease (men(SSM), RR = 1.88; 95% CI 1.08-3.01). There was also an excess of primary biliary cirrhosis (women(SSM), RR = 4.09; 95% CI 1.01-10.7), and of psoriasis (men(SSM), RR = 2.48; 95% CI 1.77-3.36), rheumatic fever (men(SSM), RR = 7.55; 95% CI 1.87-19.8), myasthenia gravis (men(SSM), RR = 5.51; 95% CI 1.36-14.4), localized scleroderma (men(SSM), RR = 7.16; 95% CI 1.18-22.6) and pemphigoid (men(SSM), RR = 6.56; 95% CI 1.08-20.6), while Dupuytren's contracture was reduced (men(SSM), RR = 0.64; 95% CI 0.39-0.99). The excess of psoriasis was restricted to same-sex married men with HIV/AIDS (men(SSM), RR = 10.5; 95% CI 6.44-15.9), whereas Graves' disease occurred in excess only among same-sex married men without HIV/AIDS (men(SSM), RR = 1.99; 95% CI 1.12-3.22). Lesbians and immunologically competent gay men in same-sex marriage face no unusual overall risk of autoimmune diseases. However, the observed increased risk of thyroid dysfunction in these lesbians and gay men deserves further study. PMID:24306355

  18. Prevalence of Thyroid Autoimmunity in Children with Celiac Disease Compared to Healthy 12-Year Olds

    PubMed Central

    Ivarsson, Anneli; Högberg, Lotta; Svensson, Johan; Carlsson, Annelie

    2014-01-01

    Objectives. Studies have suggested a correlation between untreated celiac disease and risk for other autoimmune diseases. We investigated the prevalence of thyroid autoimmunity in 12-year-old children (i) with symptomatic celiac disease diagnosed and treated with a gluten-free diet, (ii) with screening-detected untreated celiac disease, and (iii) without celiac disease. Methods. Blood samples from 12632 children were collected. All celiac disease cases, previously diagnosed and newly screening-detected, were identified. Per case, 4 referents were matched. Blood samples were analyzed for autoantibodies against thyroid peroxidase (TPOAb). The cut-off value for TPO positivity was set to 100 U/mL. Results. Altogether, 335 celiac disease cases were found. In the entire celiac disease group, 7.2% (24/335) had elevated titers of TPOAb compared to 2.8% (48/1695) of the referents. Among the previously diagnosed celiac disease cases, 7.5% (7/93, OR 2.8, 95% CI 1.2–6.4) was TPOAb positive and among screening-detected cases, 7.0% (17/242, OR 2.6, 95% CI 1.5–4.6) was TPOAb positive. Conclusion. Children with celiac disease showed a higher prevalence of thyroid autoimmunity. We could not confirm the hypothesis that untreated celiac disease is associated with increased risk of developing thyroid autoimmunity. Early initiation of celiac disease treatment might not lower the risk for other autoimmune diseases. PMID:24592326

  19. Etanercept (SB4): A Review in Autoimmune Inflammatory Diseases.

    PubMed

    Burness, Celeste B; Duggan, Sean T

    2016-08-01

    Etanercept (SB4) [Benepali(®)], a tumour necrosis factor inhibitor that is a biosimilar of reference etanercept (Enbrel(®)), is approved in the EU for use in all adult indications for which reference etanercept is approved, namely rheumatoid arthritis, axial spondyloarthritis (ankylosing spondylitis and non-radiographic axial spondyloarthritis), psoriatic arthritis, and plaque psoriasis. The approval of etanercept (SB4) was based on the results of stringent comparability exercises designed to demonstrate similarity to reference etanercept in terms of quality, biological activity, efficacy, safety, and immunogenicity. In two well-designed clinical trials, etanercept (SB4) was equivalent to reference etanercept with regard to pharmacokinetic properties in healthy volunteers and in terms of efficacy in patients with moderate to severe rheumatoid arthritis despite methotrexate therapy. Longer-term efficacy (up to 52 weeks) was also similar in both treatment groups. Etanercept (SB4) was generally well tolerated, with a similar safety profile to that of reference etanercept. Preliminary results of the open-label extension period (100 weeks) suggest that transitioning from reference etanercept to etanercept (SB4) was associated with sustained efficacy and no change in the adverse event profile or immunogenicity. In conclusion, etanercept (SB4) provides therapeutically equivalent alternative in adult patients with autoimmune inflammatory diseases requiring treatment with etanercept. PMID:27455991

  20. The many faces of Mac-1 in autoimmune disease.

    PubMed

    Rosetti, Florencia; Mayadas, Tanya N

    2016-01-01

    Mac-1 (CD11b/CD18) is a β2 integrin classically regarded as a pro-inflammatory molecule because of its ability to promote phagocyte cytotoxic functions and enhance the function of several effector molecules such as FcγR, uPAR, and CD14. Nevertheless, recent reports have revealed that Mac-1 also plays significant immunoregulatory roles, and genetic variants in ITGAM, the gene that encodes CD11b, confer risk for the autoimmune disease systemic lupus erythematosus (SLE). This has renewed interest in the physiological roles of this integrin and raised new questions on how its seemingly opposing biological functions may be regulated. Here, we provide an overview of the CD18 integrins and how their activation may be regulated as this may shed light on how the opposing roles of Mac-1 may be elicited. We then discuss studies that exemplify Mac-1's pro-inflammatory versus regulatory roles particularly in the context of IgG immune complex-mediated inflammation. This includes a detailed examination of molecular mechanisms that could explain the risk-conferring effect of rs1143679, a single nucleotide non-synonymous Mac-1 polymorphism associated with SLE.

  1. Sex bias in paediatric autoimmune disease - Not just about sex hormones?

    PubMed

    Chiaroni-Clarke, Rachel C; Munro, Jane E; Ellis, Justine A

    2016-05-01

    Autoimmune diseases affect up to 10% of the world's population, and approximately 80% of those affected are female. The majority of autoimmune diseases occur more commonly in females, although some are more frequent in males, while others show no bias by sex. The mechanisms leading to sex biased disease prevalence are not well understood. However, for adult-onset autoimmune disease, at least some of the cause is usually ascribed to sex hormones. This is because levels of sex hormones are one of the most obvious physiological differences between adult males and females, and their impact on immune system function is well recognised. While for paediatric-onset autoimmune diseases a sex bias is not as common, there are several such diseases for which one sex predominates. For example, the oligoarticular subtype of juvenile idiopathic arthritis (JIA) occurs in approximately three times more girls than boys, with a peak age of onset well before the onset of puberty, and at a time when levels of androgen and oestrogen are low and not strikingly different between the sexes. Here, we review potential explanations for autoimmune disease sex bias with a particular focus on paediatric autoimmune disease, and biological mechanisms outside of sex hormone differences.

  2. Cutaneous Manifestations of Common Liver Diseases

    PubMed Central

    Dogra, Sunil; Jindal, Rashmi

    2012-01-01

    Skin functions as a window to our overall health and a number of systemic diseases result in various cutaneous changes. Knowledge of these manifestations helps in suspecting an underlying systemic illness. Cutaneous abnormalities are quite common in patients with liver diseases and this article aims to focus on these dermatoses. Cutaneous manifestations seen in patients with liver disease though common are nonspecific. They can also be seen in patients without liver diseases and generally do not indicate about a specific underlying hepatic disorder. The presence of a constellation of signs and symptoms is more useful in pointing toward an underlying hepatobiliary condition. The commonest symptom in patients with liver disease is pruritus which is often protracted and disabling. Other common features include spider angiomas, palmar erythema, paper money skin, xanthelasmas, pigmentary changes, and nutritional deficiencies. In this article, first the common cutaneous manifestations that may be associated with liver disorders are discussed and then common liver diseases with their specific cutaneous findings are discussed. Cutaneous abnormalities may be the first clue to the underlying liver disease. Identifying them is crucial for early diagnosis and better management. PMID:25755383

  3. GFR Estimating Equations and Liver Disease.

    PubMed

    Beben, Tomasz; Rifkin, Dena E

    2015-09-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients' low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine-based estimated glomerular filtration rate (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24-hour creatinine clearance has limitations. In liver disease, all creatinine-based estimates of GFR overestimate gold standard-measured GFR, and the degree of overestimation is highest at lower measured GFR values and in more severe liver disease. Cystatin C-based eGFR has shown promise in general population studies by demonstrating less bias than creatinine-based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed, and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand kidney function in liver disease.

  4. GFR Estimating Equations and Liver Disease

    PubMed Central

    Beben, Tomasz; Rifkin, Dena E.

    2015-01-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease in order to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients’ low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine based estimated GFR (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24 hour creatinine clearance has limitations. In liver disease, all creatinine based estimates of GFR overestimate gold standard measured GFR (mGFR), and the degree of overestimation is highest at lower mGFR values and in more severe liver disease. Cystatin C based eGFR has shown promise in general population studies by demonstrating less bias than creatinine based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand renal function in liver disease. PMID:26311594

  5. [Autoimmune hepatitis].

    PubMed

    Ostojić, Rajko

    2003-01-01

    Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

  6. Diagnosis and management of polycystic liver disease.

    PubMed

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years.

  7. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  8. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease.

    PubMed

    Lucero, Catherine; Brown, Robert S

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  9. Cell and Tissue Engineering for Liver Disease

    PubMed Central

    Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

    2015-01-01

    Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

  10. Clinical presentation of metabolic liver disease.

    PubMed

    Odievre, M

    1991-01-01

    Some clinical clues should alert paediatricians to the possibility of metabolic liver diseases. They can be classified into three categories: (i) Manifestations due to hepatocellular necrosis, acute or subacute, which can reveal galactosaemia, hereditary fructose intolerance, tyrosinaemia type I, Wilson disease and alpha 1-antitrypsin deficiency. Symptoms and signs suggestive of Reye syndrome should lead to a study of fatty acid oxidation and urea cycle enzymes. All these manifestations may necessitate a rapid diagnosis and treatment when liver dysfunction is severe. (ii) Cholestatic jaundice can reveal alpha 1-antitrypsin deficiency, Byler's disease, cystic fibrosis, Niemann-Pick disease and some disorders of peroxisome biogenesis. (iii) Hepatomegaly can reveal disorders with liver damage but also storage diseases such as glycogen storage diseases, cholesteryl ester storage disease and, when associated with splenomegaly, lysosomal storage diseases. Appropriate investigations for recognizing all these entities are proposed.

  11. THE ETIOLOGY OF AUTOIMMUNE THYROID DISEASE: A STORY OF GENES AND ENVIRONMENT

    PubMed Central

    Tomer, Yaron; Huber, Amanda

    2013-01-01

    Autoimmune thyroid diseases (AITD), including Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) are prevalent autoimmune diseases, affecting up to 5% of the general population. Autoimmune thyroid diseases arise due to complex interactions between environmental and genetic factors. Significant progress has been made in our understanding of the genetic and environmental triggers contributing to AITD. However, the interactions between genes and environment are yet to be defined. Among the major AITD susceptibility genes that have been identified and characterized is the HLADR gene locus, as well as non-MHC genes including the CTLA-4, CD40, PTPN22, thyroglobulin, and TSH receptor genes. The major environmental triggers of AITD include iodine, medications, infection, smoking, and possibly stress. Recent data on the genetic predisposition to AITD lead to novel putative mechanisms by which the genetic-environmental interactions may lead to the development of thyroid autoimmunity. PMID:19307103

  12. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  13. Managing non-alcoholic fatty liver disease

    PubMed Central

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment. PMID:27439352

  14. AIRE genetic variants and predisposition to polygenic autoimmune disease: The case of Graves' disease and a systematic literature review.

    PubMed

    Colobran, Roger; Giménez-Barcons, Mireia; Marín-Sánchez, Ana; Porta-Pardo, Eduard; Pujol-Borrell, Ricardo

    2016-08-01

    Autoimmune Regulator (AIRE) is a transcriptional regulator that is crucial for establishing central tolerance as illustrated by the Mendelian Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED) syndrome associated with AIRE-inactivating recessive or dominant mutations. Polymorphisms in AIRE have been proposed to be implicated in genetic susceptibility to non-Mendelian organ specific autoimmune diseases. Because there is evidence that in predisposition to Graves' disease (GD) central tolerance is crucial, we investigated whether AIRE polymorphisms could modulate risk of GD. A case-control association study using 29 variants and conducted in 150 GD patients and 200 controls did not detect any significant association. This result is not exceptional: a systematic review of the literature, including GWAS, on the association of AIRE variants with organ specific autoimmune diseases did not show clear associations; similarly heterozygous recessive mutations are not associated to non-Mendelian autoimmunity. Dominant negative mutations of AIRE are associated to autoimmunity but as mild forms of APECED rather than to non-Mendelian organ specific autoimmunity. The lack of association of common AIRE polymorphisms with polygenic autoimmune diseases is counterintuitive as many other genes less relevant for immunological tolerance have been found to be associated. These findings give rise to the intriguing possibility that evolution has excluded functionally modifying polymorphisms in AIRE.

  15. TGF-β signalling and liver disease.

    PubMed

    Fabregat, Isabel; Moreno-Càceres, Joaquim; Sánchez, Aránzazu; Dooley, Steven; Dewidar, Bedair; Giannelli, Gianluigi; Ten Dijke, Peter

    2016-06-01

    The transforming growth factor-beta (TGF-β) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF-β functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF-β signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF-β has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF-β, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF-β may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF-β signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF-β signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state-of-the-art in the signalling pathways induced by TGF-β that are involved in different stages of liver physiology and pathology.

  16. Rheumatologic Manifestations in Iranian Patients with Autoimmune Thyroid Diseases

    PubMed Central

    Hezarkhani, Sharabeh; Aghaei, Mehrdad; Shamekhi, Maryam; Nomali, Mahin

    2014-01-01

    Background: Autoimmune thyroid diseases (ATDs) are the most common endocrine diseases which result in rheumatologic manifestations. Some studies have shown association between rheumatologic disorders and ATDs. Thus, the aim of this study was to assess the frequency of rheumatologic manifestations in patients with ATDs. Materials and Methods: In this cross-sectional descriptive study during 2010 to 2011, 65 patients with ATDs referred to the Rheumatology clinic of 5 Azar Hospital in Gorgan (North of Iran) were studied via systematic random sampling and patients with positive antithyroid peroxides (anti-TPO) were included in the study. These patients were examined by a rheumatologist for diagnosis of rheumatologic manifestations and tested for serum levels of TSH, Free T3 and T4, Anti-Nuclear Antibodies (ANAs) and Rheumatoid Factor (RF). SPSS software (version 16) and descriptive statistics were used for data analysis. Results: Nine males (14.8%) and 56 females (86.2%) with mean age of 38.81±1.44 years were studied. Overall, Rheumatologic manifestations were seen in 86.2 % (n=56). In this study, the most frequent rheumatologic manifestations were Carpal Tunnel Syndrome (36.1%) and Osteoarthritis (23%). Reynaud’s phenomenon (RP) (10.7%), Discopathy (8.9%), Fibromyalgia (5.3%), Myopathy (3.6%), Rheumatoid arthritis (3.6%) and trigger finger (3.6%) were other manifestations, respectively. Conclusion: In this region, there is a high frequency of rheumatologic manifestations in patients with ATDs. Thus, initial evaluation and regular checkings are recommended. PMID:25478383

  17. The nexus between atopic disease and autoimmunity: a review of the epidemiological and mechanistic literature.

    PubMed

    Rabin, R L; Levinson, A I

    2008-07-01

    There has been considerable interest in defining the relationship between the expression of allergic and autoimmune diseases in populations of patients. Are patients with autoimmune disease 'protected' from developing allergic (immunoglobulin E-mediated) diseases? Does the establishment of an atopic phenotype reduce the risk of the subsequent development of autoimmune diseases? Although there are clinical studies addressing this question, methodological problems, particularly in identification of atopic subjects, limits their usefulness. Moreover, an immune-based explanation of the observed epidemiological findings has relied on a paradigm that is currently undergoing increased scrutiny and modification to include newly defined effector cell subsets and the interaction between genetic and environmental factors, such as early endotoxin or mycobacterial exposure. To address this question, we reviewed a series of clinical reports that addressed coincidence or co-prevalence of atopy with four autoimmune diseases: psoriasis, rheumatoid arthritis, multiple sclerosis and type I diabetes mellitus. We present a model whereby active T helper type 1 (Th1) inflammation may suppress the development of atopy, and atopy may suppress the severity but not necessarily the onset of autoimmunity, and then discuss our model in the context of mechanisms of adaptive immunity with particular reference to the Th1/Th2 paradigms. Because the ultimate goal is to ameliorate or cure these diseases, our discussion may help to predict or interpret unexpected consequences of novel therapeutic agents used to target autoimmune or atopic diseases. PMID:18505431

  18. Gut-Liver Axis in Alcoholic Liver Disease

    PubMed Central

    Szabo, Gyongyi

    2014-01-01

    Alcoholic liver disease (ALD) has been amongst the leading causes of liver cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation suggesting a role for gut-derived “toxins” in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that is increasingly recognized as a major factor in ALD. Bacterial endotoxin, LPS, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4 (TLR4). Recent studies also demonstrated that alcohol consumption is associated with alterations in the gut microbiome and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. PMID:25447847

  19. Obesity as a Risk and Severity Factor in Rheumatic Diseases (Autoimmune Chronic Inflammatory Diseases)

    PubMed Central

    Gremese, Elisa; Tolusso, Barbara; Gigante, Maria Rita; Ferraccioli, Gianfranco

    2014-01-01

    The growing body of evidence recognizing the adipose tissue (AT) as an active endocrine organ secreting bioactive mediators involved in metabolic and inflammatory disorders, together with the global epidemic of overweight and obesity, rise obesity as a hot topic of current research. The chronic state of low-grade inflammation present in the obese condition and the multiple pleiotropic effects of adipokines on the immune system has been implicated in the pathogenesis of several inflammatory conditions including rheumatic autoimmune and inflammatory diseases. We will discuss the main relevant evidences on the role of the AT on immune and inflammatory networks and the more recent evidences regarding the effects of obesity on the incidence and outcomes of the major autoimmune chronic inflammatory diseases. PMID:25426122

  20. Clonal Evolution in Two Patients with Autoimmune Disease and Lymphoreticular Neoplasia

    PubMed Central

    Adam, M.; Thorburn, Marigold J.; Gibbs, W. N.; Brooks, S. E. H.; Hanchard, B.

    1970-01-01

    Two cases are described, one with proven lymphosarcoma and doubtful autoimmune disease, and the second with the reverse situation, in which circulating abnormal mononuclear cells showed PHA responsiveness and an abnormal chromosomal constitution (clonal evolution). These findings are discussed in the light of previous cytogenetic studies of lymphoreticular neoplasia and autoimmune disease and the relationship between these two conditions. ImagesFigs. 2-3Fig. 9Fig. 4Figs. 6-7Figs. 1,5Fig. 8 PMID:4393772

  1. Managing systemic symptoms in chronic liver disease.

    PubMed

    Newton, Julia L; Jones, David E J

    2012-01-01

    Improved medical management and the changing disease demographic mean that the majority of patients with chronic liver disease are living with the disease rather than dying from it. Historically, the perception has been that the impact of chronic liver disease is related entirely to the consequences of endstage liver disease; however, more recently a number of systemic symptoms have been recognised that can occur at any point in the natural history of chronic liver disease and which can be associated with functional impairment and reduced quality of life. The most characteristic of these systemic symptoms is fatigue, which frequently associates with sleep disturbance and autonomic dysfunction, particularly manifest as abnormality of blood pressure regulation. Cognitive symptoms can occur even in non-cirrhotic patients. Falls can present in patients with autonomic dysfunction, complicated by the presence of peripheral muscle strength problems. Importantly for clinicians managing chronic liver disease, the severity of these systemic symptoms is typically not related to liver disease severity, and therefore despite optimal liver disease management, patients can often continue to experience debilitating symptoms. The similarity in systemic symptoms between different chronic liver diseases (and indeed chronic inflammatory conditions affecting other organs) suggests the possibility of shared pathogenetic processes and raises the possibility of common management strategies, although further research is urgently needed to confirm this. In primary biliary cirrhosis, where our understanding of systemic symptoms is arguably most developed, structured management strategies have been shown to improve the quality of life of patients. It is highly likely that similar approaches will have comparable benefits for other chronic liver disease groups. Here, we review the current understanding of systemic symptoms in chronic liver disease and offer recommendations regarding the

  2. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs

    PubMed Central

    Khan, Deena; Ansar Ahmed, S.

    2015-01-01

    In recent years, IL-17A (IL-17), a pro-inflammatory cytokine, has received intense attention of researchers and clinicians alike with documented effects in inflammation and autoimmune diseases. IL-17 mobilizes, recruits and activates different cells to increase inflammation. Although protective in infections, overproduction of IL-17 promotes inflammation in autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, psoriasis, among others. Regulating IL-17 levels or action by using IL-17-blocking antibodies or IL-17R antagonist has shown to attenuate experimental autoimmune diseases. It is now known that in addition to IL-17-specific transcription factor, RORγt, several other transcription factors and select microRNAs (miRNA) regulate IL-17. Given that miRNAs are dysregulated in autoimmune diseases, a better understanding of transcriptional factors and miRNA regulation of IL-17 expression and function will be essential for devising potential new therapies. In this review, we will overview IL-17 induction and function in relation to autoimmune diseases. In addition, current findings on transcriptional regulation of IL-17 induction and plausible interplay between IL-17 and miRNA in autoimmune diseases are highlighted. PMID:26236331

  3. M. paratuberculosis Heat Shock Protein 65 and Human Diseases: Bridging Infection and Autoimmunity

    PubMed Central

    Dow, Coad Thomas

    2012-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) is the known infectious cause of Johne's disease, an enteric inflammatory disease mostly studied in ruminant animals. MAP has also been implicated in the very similar Crohn's disease of humans as well as sarcoidosis. Recently, MAP has been associated with juvenile sarcoidosis (Blau syndrome), autoimmune diabetes, autoimmune thyroiditis, and multiple sclerosis. While it is intuitive to implicate MAP in granulomatous diseases where the microbe participates in the granuloma, it is more difficult to assign a role for MAP in diseases where autoantibodies are a primary feature. MAP may trigger autoimmune antibodies via its heat shock proteins. Mycobacterial heat shock protein 65 (HSP65) is an immunodominant protein that shares sequential and conformational elements with several human host proteins. This molecular mimicry is the proposed etiopathology by which MAP stimulates autoantibodies associated with autoimmune (type 1) diabetes, autoimmune (Hashimoto's) thyroiditis, and multiple sclerosis. This paper proposes that MAP is a source of mycobacterial HSP65 and acts as a trigger of autoimmune disease. PMID:23056923

  4. [Occupational liver diseases: (author's transl)].

    PubMed

    Kuntz, H D; May, B

    1980-07-18

    A large number of exogenous substances with potential liver toxicity are to be found in work places and in the environment. Decisive importance is ascribed to regular supervision of exposed persons and adhering to the appropriate safety provisions without being able to ensure reliable prevention of toxic liver damage thereby. The prognosis of occupational toxic liver damage is good if recognition is timely and the causal noxae are eliminated. The aim of all diagnostic and prophylactic efforts must be rehabilitation, in addition to specific occupational medical and hygienic measures.

  5. Telomeres, NAFLD and Chronic Liver Disease.

    PubMed

    Donati, Benedetta; Valenti, Luca

    2016-01-01

    Telomeres consist of repeat DNA sequences located at the terminal portion of chromosomes that shorten during mitosis, protecting the tips of chromosomes. During chronic degenerative conditions associated with high cell replication rate, progressive telomere attrition is accentuated, favoring senescence and genomic instability. Several lines of evidence suggest that this process is involved in liver disease progression: (a) telomere shortening and alterations in the expression of proteins protecting the telomere are associated with cirrhosis and hepatocellular carcinoma; (b) advanced liver damage is a feature of a spectrum of genetic diseases impairing telomere function, and inactivating germline mutations in the telomerase complex (including human Telomerase Reverse Transcriptase (hTERT) and human Telomerase RNA Component (hTERC)) are enriched in cirrhotic patients independently of the etiology; and (c) experimental models suggest that telomerase protects from liver fibrosis progression. Conversely, reactivation of telomerase occurs during hepatocarcinogenesis, allowing the immortalization of the neoplastic clone. The role of telomere attrition may be particularly relevant in the progression of nonalcoholic fatty liver, an emerging cause of advanced liver disease. Modulation of telomerase or shelterins may be exploited to prevent liver disease progression, and to define specific treatments for different stages of liver disease. PMID:26999107

  6. Vitamin D deficiency in chronic liver disease

    PubMed Central

    Iruzubieta, Paula; Terán, Álvaro; Crespo, Javier; Fábrega, Emilio

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required. PMID:25544877

  7. Molecular mimicry: its evolution from concept to mechanism as a cause of autoimmune diseases.

    PubMed

    Oldstone, Michael B A

    2014-06-01

    On a clonal level, certain antibodies and T cells can interact with dissimilar antigens found in microbes and in host cells. More than 5% of over 800 monoclonal antibodies derived from multiple RNA and DNA viruses, as well as from a large number of T cell clones, engage in such interactions. Several of these cross-reactions, which we termed molecular mimicry, are against unique host proteins involved in autoimmune responses and diseases. Thus, molecular mimicry initiated as a host response to a virus or a microbial infection, but alternatively cross-reacting with an appropriate host-antigen, can be a mechanism for instigating an autoimmune disease. Molecular mimicry provides an explanation for the genetic observation that identical twins rarely manifest the same autoimmune disease and the documented epidemiologic evidence that microbial and/or viral infections often precede autoimmune disorders. PMID:24694269

  8. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease.

    PubMed

    Ellebrecht, Christoph T; Bhoj, Vijay G; Nace, Arben; Choi, Eun Jung; Mao, Xuming; Cho, Michael Jeffrey; Di Zenzo, Giovanni; Lanzavecchia, Antonio; Seykora, John T; Cotsarelis, George; Milone, Michael C; Payne, Aimee S

    2016-07-01

    Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. Here, we show that in the antibody-mediated autoimmune disease pemphigus vulgaris (PV), autoantigen-based chimeric immunoreceptors can direct T cells to kill autoreactive B lymphocytes through the specificity of the B cell receptor (BCR). We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. Dsg3 CAAR-T cells exhibit specific cytotoxicity against cells expressing anti-Dsg3 BCRs in vitro and expand, persist, and specifically eliminate Dsg3-specific B cells in vivo. CAAR-T cells may provide an effective and universal strategy for specific targeting of autoreactive B cells in antibody-mediated autoimmune disease. PMID:27365313

  9. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism. PMID:26447960

  10. Role of Gut Microbiota in Liver Disease.

    PubMed

    Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

    2015-01-01

    Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

  11. Plasticity of Th17 Cells in Autoimmune Kidney Diseases.

    PubMed

    Krebs, Christian F; Turner, Jan-Eric; Paust, Hans-Joachim; Kapffer, Sonja; Koyro, Tobias; Krohn, Sonja; Ufer, Friederike; Friese, Manuel A; Flavell, Richard A; Stockinger, Brigitta; Steinmetz, Oliver M; Stahl, Rolf A K; Huber, Samuel; Panzer, Ulf

    2016-07-15

    The ability of CD4(+) T cells to differentiate into pathogenic Th1 and Th17 or protective T regulatory cells plays a pivotal role in the pathogenesis of autoimmune diseases. Recent data suggest that CD4(+) T cell subsets display a considerable plasticity. This plasticity seems to be a critical factor for their pathogenicity, but also for the potential transition of pathogenic effector T cells toward a more tolerogenic phenotype. The aim of the current study was to analyze the plasticity of Th17 cells in a mouse model of acute crescentic glomerulonephritis and in a mouse chronic model of lupus nephritis. By transferring in vitro generated, highly purified Th17 cells and by using IL-17A fate reporter mice, we demonstrate that Th17 cells fail to acquire substantial expression of the Th1 and Th2 signature cytokines IFN-γ and IL-13, respectively, or the T regulatory transcription factor Foxp3 throughout the course of renal inflammation. In an attempt to therapeutically break the stability of the Th17 phenotype in acute glomerulonephritis, we subjected nephritic mice to CD3-specific Ab treatment. Indeed, this treatment induced an immunoregulatory phenotype in Th17 cells, which was marked by high expression of IL-10 and attenuated renal tissue damage in acute glomerulonephritis. In summary, we show that Th17 cells display a minimum of plasticity in acute and chronic experimental glomerulonephritis and introduce anti-CD3 treatment as a tool to induce a regulatory phenotype in Th17 cells in the kidney that may be therapeutically exploited.

  12. Clinical differences between alcoholic liver disease and nonalcoholic fatty liver disease.

    PubMed

    Toshikuni, Nobuyuki; Tsutsumi, Mikihiro; Arisawa, Tomiyasu

    2014-07-14

    Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Although most subjects with excessive alcohol or food intake experience simple hepatic steatosis, a small percentage of individuals will develop progressive liver disease. Notably, both ALD and NAFLD are frequently accompanied by extrahepatic complications, including cardiovascular disease and malignancy. The survival of patients with ALD and NAFLD depends on various disease-associated conditions. This review delineates the clinical characteristics and outcomes of patients with ALD and NAFLD by comparing their epidemiology, the factors associated with disease susceptibility and progression, and the predictors and characteristics of outcomes. A comprehensive understanding of the characteristics and outcomes of ALD and NAFLD is imperative in the management of these chronic liver diseases. PMID:25024597

  13. Exome Analysis of Patients with Concurrent Pediatric Inflammatory Bowel Disease and Autoimmune Disease

    PubMed Central

    Andreoletti, Gaia; Ashton, James J.; Coelho, Tracy; Willis, Claire; Haggarty, Rachel; Gibson, Jane; Holloway, John; Batra, Akshay; Afzal, Nadeem A.; Beattie, Robert Mark

    2015-01-01

    Background: Pediatric Inflammatory Bowel Disease (PIBD) is a chronic condition seen in genetically predisposed individuals. Genome-wide association studies have implicated >160 genomic loci in IBD with many genes coding for proteins in key immune pathways. This study looks at autoimmune disease burden in patients diagnosed with PIBD and interrogates exome data of a subset of patients. Methods: Patients were recruited from the Southampton Genetics of PIBD cohort. Clinical diagnosis of autoimmune disease in these individuals was ascertained from medical records. For a subset of patients with PIBD and concurrent asthma, exome data was interrogated to ascertain the burden of pathogenic variants within genes implicated in asthma. Association testing was conducted between cases and population controls using the SKAT-O test. Results: Forty-nine (28.3%) PIBD children (18.49% CD, 8.6% UC, and 21.15% IBDU patients) had a concurrent clinical diagnosis of at least one other autoimmune disorder; asthma was the most prevalent, affecting 16.2% of the PIBD cohort. Rare and common variant association testing revealed 6 significant genes (P < 0.05) before Bonferroni adjustment. Three of these genes were previously implicated in both asthma and IBD (ZPBP2 IL1R1, and IL18R1) and 3 in asthma only (PYHIN1, IL2RB, and GSTP1). Conclusions: One-third of our cohort had a concurrent autoimmune condition. We observed higher incidence of asthma compared with the overall pediatric prevalence. Despite a small sample size, SKAT-O evaluated a significant burden of rare and common mutations in 6 genes. Variant burden suggests that a systemic immune dysregulation rather than organ-specific could underpin immune dysfunction for a subset of patients. PMID:25895113

  14. Genetic variations in ZFP36 and their possible relationship to autoimmune diseases.

    PubMed

    Carrick, Danielle Mercatante; Chulada, Patricia; Donn, Rachelle; Fabris, Martina; McNicholl, Janet; Whitworth, William; Blackshear, Perry J

    2006-05-01

    The ZFP36 gene codes for TTP, a regulator of TNF alpha. In mice, TTP deficiency results in a systemic autoimmune inflammatory syndrome with severe arthritis. We hypothesized that genetic variations in ZFP36 are associated with autoimmune disease in humans. The primary objective of this study was to identify human ZFP36 genetic variants in autoimmune disease cases and controls, determine their frequencies in a general clinic population, and construct haplotypes. We resequenced ZFP36 in 316 individuals with autoimmune diseases and identified 28 polymorphisms and determined the frequency of all the known ZFP36 polymorphisms in 484 participants of the Environmental Polymorphism Registry, a regional registry being conducted by the NIEHS. Based on the sequence-verified ZFP36 genotypes, 34 haplotypes were constructed. As a secondary objective, we examined autoimmune disease cases and controls for potential ZFP36 genetic associations. One novel polymorphism, ZFP36*8, a C to T transition in the protein coding domain, was significantly associated with rheumatoid arthritis (RA) in African-Americans (RR=1.23, 95% CI: 1.11-1.36). The data presented here suggest a tentative association between ZFP36 and RA. This finding, as well as the ZFP36 polymorphisms and haplotypes identified here, should form the basis for future association studies in autoimmune diseases.

  15. Dame Sheila Sherlock: pioneer in liver diseases.

    PubMed

    Ellis, Harold

    2009-04-01

    Within living memory of some of us, liver disease was a Cinderella subject. If you look up the first edition of the standard medical textbook of the time, Sir William Osler's 'Principles and Practice of Medicine', published in 1892, you will find a mere 24 of its 1079 pages devoted to the liver, compared with 38 pages on typhoid fever alone; and matters hardly changed throughout the first half of the 20th century. Although 'cirrhosis' and 'hepatitis' were well recognised conditions when I was a house surgeon in 1948, their classification, aetiologies, detailed pathology and management were little understood, while laboratory investigations of the liver diseases were few and non-specific.

  16. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    MedlinePlus

    ... Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/Pacific Islanders were seven times ... At a glance – Cancer Rates for Native Hawaiian/Pacific Islander Liver & IBD Cancer Incidence Rates per 100, ...

  17. Microbiomic and Posttranslational Modifications as Preludes to Autoimmune Diseases.

    PubMed

    Opdenakker, Ghislain; Proost, Paul; Van Damme, Jo

    2016-09-01

    Diagnosis and treatment of autoimmunity has mainly relied on adaptive immunity. Infection and inflammation induce cytokines and chemokines and activate myeloid cells to release enzymes. Proteases cleave host proteins into a molar excess of remnant peptides. Additional enzymes modify these peptides into putative autoantigens prior to T and B cell activation. We propose that post-translational modifications may be a means of generating auto-reactive peptides. Microbes also provide proteases and modifying enzymes to the host, and we posit that this may result in autoantigen generation. This could help explain, at least in part, the recently discovered connections between microbiota and autoimmunity. Better explorations of the innate prelude phase of autoimmunity in conjunction with environmental factors might provide novel, broadly applicable therapies. PMID:27491925

  18. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

    PubMed Central

    Jeffery, Hannah C.; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients.

  19. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives

    PubMed Central

    Jeffery, Hannah C.; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID:27656181

  20. Clinical Potential of Regulatory T Cell Therapy in Liver Diseases: An Overview and Current Perspectives.

    PubMed

    Jeffery, Hannah C; Braitch, Manjit Kaur; Brown, Solomon; Oo, Ye Htun

    2016-01-01

    The increasing demand for liver transplantation and the decline in donor organs has highlighted the need for alternative novel therapies to prevent chronic active hepatitis, which eventually leads to liver cirrhosis and liver cancer. Liver histology of chronic hepatitis is composed of both effector and regulatory lymphocytes. The human liver contains different subsets of effector lymphocytes that are kept in check by a subpopulation of T cells known as Regulatory T cells (Treg). The balance of effector and regulatory lymphocytes generally determines the outcome of hepatic inflammation: resolution, fulminant hepatitis, or chronic active hepatitis. Thus, maintaining and adjusting this balance is crucial in immunological manipulation of liver diseases. One of the options to restore this balance is to enrich Treg in the liver disease patients. Advances in the knowledge of Treg biology and development of clinical grade isolation reagents, cell sorting equipment, and good manufacturing practice facilities have paved the way to apply Treg cells as a potential therapy to restore peripheral self-tolerance in autoimmune liver diseases (AILD), chronic rejection, and posttransplantation. Past and on-going studies have applied Treg in type-1 diabetes mellitus, systemic lupus erythematosus, graft versus host diseases, and solid organ transplantations. There have not been any new therapies for the AILD for more than three decades; thus, the clinical potential for the application of autologous Treg cell therapy to treat autoimmune liver disease is an attractive and novel option. However, it is fundamental to understand the deep immunology, genetic profiles, biology, homing behavior, and microenvironment of Treg before applying the cells to the patients. PMID:27656181

  1. CD8 T cells mediate direct biliary ductule damage in NOD autoimmune biliary disease

    PubMed Central

    Yang, Guo-Xiang; Wu, Yuehong; Tsukamoto, Hiroki; Leung, Patrick S.; Lian, Zhe-Xiong; Rainbow, Daniel B.; Hunter, Kara M.; Morris, Gerard A.; Lyons, Paul A.; Peterson, Laurence B.; Wicker, Linda S.; Gershwin, M.E.; Ridgway, William M.

    2016-01-01

    We previously described the NOD.c3c4 mouse, which is protected from type 1 diabetes (T1D) due to protective alleles at multiple insulin-dependent diabetes (Idd) genes, but develops autoimmune biliary disease (ABD) resembling primary biliary cirrhosis (PBC). Here we characterize the NOD.ABD strain, which is genetically-related to the NOD.c3c4 strain but develops both ABD and T1D. Histologically, NOD.ABD biliary disease is indistinguishable from that in NOD.c3c4 mice. The frequency of effector memory (CD44+CD62L-) and central memory (CD44+CD62L+) CD8 T cells is significantly increased in the intrahepatic lymphocyte fraction of NOD.ABD mice, and NOD.ABD CD8 T cells produce more IFN-γ and TNF-α, compared to controls. NOD.ABD splenocytes can transfer ABD and T1D to NOD.c3c4 scid mice, but only T1D to NOD scid mice, suggesting that the genetic origin of the target organ and/or its innate immune cells is critical to disease pathogenesis. The disease transfer model, importantly, shows that biliary duct damage (characteristic of PBC) and inflammation precede biliary epithelial cell proliferation. Unlike T1D where both CD4 and CD8 T cells are required for disease transfer, purified NOD.ABD CD8 T cells can transfer liver inflammation into NOD.c3c4 scid recipients, and disease transfer is ameliorated by co-transferring T regulatory cells. Unlike NOD.c3c4 mice, NOD.ABD mice do not develop antinuclear or anti-Smith autoantibodies; however, NOD.ABD mice do develop the anti-pyruvate dehydrogenase antibodies typical of human PBC. The NOD.ABD strain is a model of immune dysregulation affecting two organ systems, most likely by mechanisms that do not completely coincide. PMID:21169553

  2. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  3. Probiotics and Nonalcoholic Fatty liver Disease

    PubMed Central

    Eslamparast, Tannaz; Eghtesad, Sareh; Hekmatdoost, Azita; Poustchi, Hossein

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, both in adults and in children. NAFLD represents a spectrum of liver diseases that range from hepatic steatosis to steatohepatitis and cirrhosis. However, NAFLD is more prevalent in overweight and obese individuals. Evidences thus far suggest that hepatic triglyceride accumulation is not always derived from obesity; gut microbiota can also play a role in the development of insulin resistance, hepatic steatosis, necroinflammation and fibrosis. On the other hand, probiotics can strengthen the intestinal wall, reducing its permeability, bacterial translocation, and endotoxemia according to animal and human studies. They can also reduce oxidative and inflammatory liver damage, while improving the histological state in certain situations. This review article focuses on research that has been conducted on probiotics and NAFLD, highlighting their efficacy as a novel therapeutic option for the treatment of this condition. PMID:24829682

  4. Fas deficiency in mice with the Balb/c background induces blepharitis with allergic inflammation and hyper-IgE production in conjunction with severe autoimmune disease.

    PubMed

    Takahashi, Suzuka; Futatsugi-Yumikura, Shizue; Fukuoka, Ayumi; Yoshimoto, Tomohiro; Nakanishi, Kenji; Yonehara, Shin

    2013-05-01

    Fas (CD95) is a cell surface death receptor belonging to the tumor necrosis factor receptor superfamily, which mediates apoptosis-inducing signaling when activated by Fas ligand or its agonistic antibody. lpr mice with a loss of apoptosis-inducing function mutation in the Fas gene develop systemic autoimmune disease and lymphadenopathy but not allergic inflammation. In the case of Fas mutations including lpr and knockout (KO), background genes determine the incidence and severity of lymphadenopathy and histopathological manifestation of systemic autoimmunity: MRL-lpr/lpr mice and C57BL/6-lpr/lpr or C57BL/6 Fas KO mice develop severe and minimum disease, respectively. We generated Fas KO mice with the Balb/c background that show severer autoimmune phenotypes than MRL-lpr/lpr mice, such as critical infiltration of mononuclear cells into lung, liver and spleen, elevated serum levels of auto-antibodies and a decreased life span. To our astonishment, Balb/c Fas KO mice spontaneously develop blepharitis with not only autoimmune inflammation with deposition of auto-antibody but also allergic inflammation with infiltration by eosinophils and mast cells and show the capacity to strongly increase serum level of IgE and IgG1 along with their aging. Thus, Fas expression regulates development of not only autoimmune disease but also allergic inflammation.

  5. De novo autoimmune hepatitis following liver transplantation for primary biliary cirrhosis: an unusual cause of late grafts dysfunction

    PubMed Central

    Ennaifer, Rym; Ayadi, Hend; Romdhane, Haifa; Cheikh, Meriem; Mestiri, Hafedh; Khalfallah, Taher; Hadj, Najet Bel

    2015-01-01

    De novo autoimmune hepatitis (AIH) is a rare disorder first described in 1998. It occurs in patients who underwent liver transplantation for a different etiology. We present the case of a 56-year-old woman who was diagnosed with primary biliary cirrhosis and had liver transplantation for refractory pruritis. Seven years after transplantation, she presented alterations in the hepatic profile with hypertransaminasemia, elevated alkaline phosphatase and gamma-glutamyl-transferase. Her liver functions test also showed elevated IgG levels. Serum autoantibodies were negative except for antimitochondrial antibodies. Histological findings indicated features of AIH without bile duct damage or loss. She had a pretreatment AIH score of 13 points and a post treatment score of 15 points according to the International AIH Group. The patient was treated effectively with prednisolone and her liver function and globulin levels rapidly returned to normal. PMID:26401196

  6. The mechanisms and applications of T cell vaccination for autoimmune diseases: a comprehensive review.

    PubMed

    Huang, Xin; Wu, Haijing; Lu, Qianjin

    2014-10-01

    Autoimmune diseases (ADs) are a spectrum of diseases originating from loss of immunologic self-tolerance and T cell abnormal autoreactivity, causing organ damage and death. However, the pathogenic mechanism of ADs remains unclear. The current treatments of ADs include nonsteroidal anti-inflammatory drugs (NSAIDS), antimalarials, corticosteroids, immunosuppressive drugs, and biological therapies. With the need to prevent side effects resulting from current treatments and acquire better clinical remission, developing a novel pharmaceutical treatment is extremely urgent. The concept of T cell vaccination (TCV) has been raised as the finding that immunization with attenuated autoreactive T cells is capable of inducing T cell-dependent inhibition of autoimmune responses. TCV may act as an approach to control unwanted adaptive immune response through eliminating the autoreactive T cells. Over the past decades, the effect of TCV has been justified in several animal models of autoimmune diseases including experimental autoimmune encephalomyelitis (EAE), murine autoimmune diabetes in nonobese diabetic (NOD) mice, collagen-induced arthritis (CIA), and so on. Meanwhile, clinical trials of TCV have confirmed the safety and efficacy in corresponding autoimmune diseases ranging from multiple sclerosis (MS) to systemic lupus erythematosus (SLE). This review aims to summarize the ongoing experimental and clinical trials and elucidate possible molecule mechanisms of TCV.

  7. How to Diagnose Nonalcoholic Fatty Liver Disease.

    PubMed

    de Alwis, Nimantha M W; Anstee, Quentin M; Day, Christopher P

    2016-01-01

    Patients with nonalcoholic fatty liver disease (NAFLD) are asymptomatic and present with either unexplained abnormal liver blood tests or a bright liver on ultrasonography. Some patients will have normal liver blood tests raising the issue of whether patients with risk factors for NAFLD (diabetes and/or metabolic syndrome [MS]) should be screened for its presence with biomarkers, such as the fatty liver index (FLI). The diagnosis of NAFLD requires the exclusion of other causes of chronic liver disease and steatosis, especially heavy alcohol consumption and viral hepatitis particularly HCV genotype 3. Diagnostic work-up should include evaluation of family and personal history of components of the MS and assessment of liver tests, fasting blood glucose, triglycerides and HDL levels. A drug history is important due to a number being associated with steatosis. To confirm the diagnosis of NAFLD and quantify steatosis, ultrasound (US) and MRI-based techniques are available but none are in routine use outside clinical trials. Standard US is no more accurate than biomarkers such as FLI. The accurate staging of NAFLD requires liver biopsy; however, this is clearly impractical for such a prevalent disease. Accordingly, a number of imaging and blood-based biomarker tests have been evaluated. While none have proved reliable for the diagnosis of nonalcoholic steatohepatitis, several have proved accurate in diagnosing the presence of stage 3 or 4 fibrosis, including the NAFLD fibrosis score, fibrosis-4 and the enhanced liver fibrosis test. Of the imaging techniques, elastography has received the most attention and is being used in routine clinical practice. US acoustic radiation force impulse imaging, and MR-based elastography have recently been described but none are sufficiently accurate to replace liver biopsy for clinical trials as yet or are cost effective for use in routine clinical settings. PMID:27547937

  8. Autoimmune diseases — connecting risk alleles with molecular traits of the immune system

    PubMed Central

    Gutierrez-Arcelus, Maria; Rich, Stephen S.; Raychaudhuri, Soumya

    2016-01-01

    Genome-wide strategies have driven the discovery of more than 300 susceptibility loci for autoimmune diseases. However, for almost all loci, understanding of the mechanisms leading to autoimmunity remains limited, and most variants that are likely to be causal are in non-coding regions of the genome. A critical next step will be to identify the in vivo and ex vivo immunophenotypes that are affected by risk variants. To do this, key cell types and cell states that are implicated in autoimmune diseases will need to be defined. Functional genomic annotations from these cell types and states can then be used to resolve candidate genes and causal variants. Together with longitudinal studies, this approach may yield pivotal insights into how autoimmunity is triggered. PMID:26907721

  9. 76 FR 13111 - Compassionate Allowances for Autoimmune Disease, Office of the Commissioner; Hearing

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... ADMINISTRATION 20 CFR Parts 404, 405, and 416 Compassionate Allowances for Autoimmune Disease, Office of the... diseases and other serious medical conditions that we should consider under the Compassionate Allowance process. These hearings concerned rare diseases, cancers, traumatic brain injury and stroke,...

  10. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers.

  11. Mucosal-associated invariant T cells in autoimmunity, immune-mediated diseases and airways disease.

    PubMed

    Hinks, Timothy S C

    2016-05-01

    Mucosal-associated invariant T (MAIT) cells are a novel class of innate-like T cells, expressing a semi-invariant T-cell receptor (TCR) and able to recognize small molecules presented on the non-polymorphic MHC-related protein 1. Their intrinsic effector-memory phenotype, enabling secretion of pro-inflammatory cytokines, and their relative abundance in humans imply a significant potential to contribute to autoimmune processes. However, as MAIT cells were unknown until recently and specific immunological tools were unavailable, little is known of their roles in disease. Here I review observations from clinical studies and animal models of autoimmune and immune-mediated diseases including the roles of MAIT cells in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and airways diseases. MAIT cell deficiencies are frequently observed in peripheral blood, and at sites of disease such as the airways in asthma. However, MAIT cells have a specific sensitivity to suppression by therapeutic corticosteroids that may confound many of these observations, as may the tendency of the surface marker CD161 to activation-induced down-regulation. Nonetheless, the dependence on bacteria for the development of MAIT cells suggests a potentially important protective role linking the influences of early life microbial exposures and subsequent development of autoimmunity. Conversely, MAIT cells could contribute to chronic inflammation either through TCR-independent activation, or potentially by TCR recognition of as yet undiscovered ligands. Future research will be greatly facilitated by the immunological tools that are now available, including murine genetic models and human and murine specific tetramers. PMID:26778581

  12. Unresolved issues in theories of autoimmune disease using myocarditis as a framework.

    PubMed

    Root-Bernstein, Robert; Fairweather, DeLisa

    2015-06-21

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related.

  13. Unresolved issues in theories of autoimmune disease using myocarditis as a framework

    PubMed Central

    Root-Bernstein, Robert; Fairweather, DeLisa

    2014-01-01

    Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related. PMID:25484004

  14. Hepatic inflammation and progressive liver fibrosis in chronic liver disease

    PubMed Central

    Czaja, Albert J

    2014-01-01

    Chronic liver inflammation drives hepatic fibrosis, and current immunosuppressive, anti-inflammatory, and anti-viral therapies can weaken this driver. Hepatic fibrosis is reversed, stabilized, or prevented in 57%-79% of patients by conventional treatment regimens, mainly by their anti-inflammatory actions. Responses, however, are commonly incomplete and inconsistently achieved. The fibrotic mechanisms associated with liver inflammation have been clarified, and anti-fibrotic agents promise to improve outcomes as adjunctive therapies. Hepatitis C virus and immune-mediated responses can activate hepatic stellate cells by increasing oxidative stress within hepatocytes. Angiotensin can be synthesized by activated hepatic stellate cells and promote the production of reactive oxygen species. Anti-oxidants (N-acetylcysteine, S-adenosyl-L-methionine, and vitamin E) and angiotensin inhibitors (losartin) have had anti-fibrotic actions in preliminary human studies, and they may emerge as supplemental therapies. Anti-fibrotic agents presage a new era of supplemental treatment for chronic liver disease. PMID:24627588

  15. Behçet's disease diagnosed after acute HIV infection: viral replication activating underlying autoimmunity?

    PubMed

    Roscoe, Clay; Kinney, Rebecca; Gilles, Ryan; Blue, Sky

    2015-05-01

    Behçet's disease is an autoimmune systemic vasculitis that can occur after exposure to infectious agents. Behçet's disease also has been associated with HIV infection, including de novo development of this condition during chronic HIV infection and resolution of Behçet's disease symptoms following initiation of antiretroviral therapy. We describe a patient who presented with systemic vasculitis with skin and mucous membrane ulcerations in the setting of acute HIV infection, who was eventually diagnosed with Behçet's disease, demonstrating a possible link between acute HIV infection, immune activation and development of autoimmunity.

  16. Management of rheumatic and autoimmune blistering disease in pregnancy and postpartum.

    PubMed

    Wan, Joy; Imadojemu, Sotonye; Werth, Victoria P

    2016-01-01

    The treatment of rheumatic and autoimmune skin disease in women who are pregnant or of childbearing potential can present challenges to the dermatologist. We discuss the current approaches to treating lupus erythematosus, antiphospholipid antibody syndrome, dermatomyositis, morphea and systemic sclerosis, mixed connective tissue disease, rheumatoid arthritis, and autoimmune blistering disease in such patients. In the appropriate setting, topical and systemic corticosteroids, hydroxychloroquine, dapsone, azathioprine, and ultraviolet B phototherapy may be safely and cautiously used during pregnancy. Considerations about contraception, planned conception, therapeutic options, and disease control are paramount in optimizing pregnancy outcomes and minimizing risks to both mother and fetus. PMID:27265072

  17. Is vitamin D a player or not in the pathophysiology of autoimmune thyroid diseases?

    PubMed

    D'Aurizio, Federica; Villalta, Danilo; Metus, Paolo; Doretto, Paolo; Tozzoli, Renato

    2015-05-01

    1,25-Dihydroxyvitamin D is a steroid hormone derived from vitamin D, playing an important role in maintaining an adequate serum level of calcium and phosphorus. It is now clear that vitamin D exerts an endocrine action on the cells of the immune system, generating anti-inflammatory and immunoregulatory effects. The mechanisms underlying the role of vitamin D in autoimmunity are not completely understood. Lower vitamin D levels have been found in several autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases, autoimmune thyroid diseases (i.e. Hashimoto's thyroiditis and Graves' disease) and autoimmune gastritis. Several genetic studies have demonstrated an association between thyroid autoimmunity susceptibility and gene polymorphisms of vitamin D receptor, vitamin D binding protein, 1-alpha-hydroxylase and 25-hydroxylase. Of note, some papers do not confirm this connection. With regard to the role of vitamin D in autoimmune thyroid diseases, available data remain controversial. Only few reports have analyzed the supposed association between autoimmune thyroid diseases and vitamin D concentration with inconclusive results. In our experience, low serum levels of vitamin D do not correlate either with Hashimoto's thyroiditis or with Graves' disease. The inability to achieve an unambiguous conclusion is in part due to the limitations in study design. In fact, most of the studies are cross-sectional surveys with a small number of subjects. In addition, the heterogeneity of the study population, seasonal variation of blood sampling, inter-method analytical variability of vitamin D assays and different definitions of vitamin D deficiency/insufficiency contribute to contradicting results. Therefore, further randomized, controlled, prospective trials are needed in order to demonstrate the causality of vitD in AITD and consequently the role of vitamin D

  18. Annotation: PANDAS--A Model for Human Autoimmune Disease

    ERIC Educational Resources Information Center

    Swedo, Susan E.; Grant, Paul J.

    2005-01-01

    Background: Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus infections (PANDAS) is a recently recognized syndrome in which pre-adolescent children have abrupt onsets of tics and/or obsessive-compulsive symptoms, a recurring and remitting course of illness temporally related to streptococcal infections, and associated…

  19. Antigen Presentation, Autoantigens, and Immune Regulation in Multiple Sclerosis and Other Autoimmune Diseases

    PubMed Central

    Riedhammer, Christine; Weissert, Robert

    2015-01-01

    Antigen presentation is in the center of the immune system, both in host defense against pathogens, but also when the system is unbalanced and autoimmune diseases like multiple sclerosis (MS) develop. It is not just by chance that a major histocompatibility complex gene is the major genetic susceptibility locus in MS; a feature that MS shares with other autoimmune diseases. The exact etiology of the disease, however, has not been fully understood yet. T cells are regarded as the major players in the disease, but most probably a complex interplay of altered central and peripheral tolerance mechanisms, T-cell and B-cell functions, characteristics of putative autoantigens, and a possible interference of environmental factors like microorganisms are at work. In this review, new data on all these different aspects of antigen presentation and their role in MS will be discussed, probable autoantigens will be summarized, and comparisons to other autoimmune diseases will be drawn. PMID:26136751

  20. The gut microbiota and liver disease

    PubMed Central

    Llorente, Cristina; Schnabl, Bernd

    2015-01-01

    The leaky gut hypothesis links translocating microbial products with the onset and progression of liver disease, and for a long time was considered one of its major contributors. However, a more detailed picture of the intestinal microbiota contributing to liver disease started to evolve. The gut is colonized by trillions of microbes that aid in digestion, modulate immune response, and generate a variety of products that result from microbial metabolic activities. These products together with host-bacteria interactions influence both normal physiology and disease susceptibility. A disruption of the symbiosis between microbiota and host is known as dysbiosis and can have profound effects on health. Qualitative changes such as increased proportions of harmful bacteria and reduced levels of beneficial bacteria, and also quantitative changes in the total amount of bacteria (overgrowth) have been associated with liver disease. Understanding the link between the pathophysiology of liver diseases and compositional and functional changes of the microbiota will help in the design of innovative therapies. In this review, we focus on factors resulting in dysbiosis, and discuss how dysbiosis can disrupt intestinal homeostasis and contribute to liver disease. PMID:26090511

  1. [Function of zinc in liver disease].

    PubMed

    Katayama, Kazuhiro

    2016-07-01

    Zinc deficiency is highly prevalent in cirrhotic patients, and contributes to several clinical symptoms such as hepatic encephalopathy and liver fibrosis. Ammonia is detoxified in liver to urea through urea cycle, and is also detoxified in extrahepatic tissue to glutamine through glutamine synthetase. The reduced ability of ammonia detoxification in liver cirrhosis is ascribed to zinc deficiency, because a member of urea cycle, ornithine transcarbamylase is a zinc enzyme. In this condition, glutamine synthesis is enhanced, which enables the body, at least temporarily, to suppress the increase of ammonia. However, the glutamine is metabolized predominantly in enterocyte to ammomia and glutamate, indicating that a vicious cycle in glutamine synthesis and glutamine breakdown occurs in liver cirrhosis. Attention should be given to the clinical significance of zinc in liver diseases. PMID:27455801

  2. Hepatocyte cell therapy in liver disease.

    PubMed

    Bartlett, David Christopher; Newsome, Philip N

    2015-01-01

    Liver disease is a leading cause of morbidity and mortality. Liver transplantation remains the only proven treatment for end-stage liver failure but is limited by the availability of donor organs. Hepatocyte cell therapy, either with bioartificial liver devices or hepatocyte transplantation, may help address this by delaying or preventing liver transplantation. Early clinical studies have shown promising results, however in most cases, the benefit has been short lived and so further research into these therapies is required. Alternative sources of hepatocytes, including stem cell-derived hepatocytes, are being investigated as the isolation of primary human hepatocytes is limited by the same shortage of donor organs. This review summarises the current clinical experience of hepatocyte cell therapy together with an overview of possible alternative sources of hepatocytes. Current and future areas for research that might lead towards the realisation of the full potential of hepatocyte cell therapy are discussed. PMID:26212798

  3. New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland.

    PubMed

    Kayes, Timothy Daniel; Weisman, Gary A; Camden, Jean M; Woods, Lucas T; Bredehoeft, Cole; Downey, Edward F; Cole, James; Braley-Mullen, Helen

    2016-09-15

    Sixty to seventy percent of IFN-γ(-/-) NOD.H-2h4 mice given sodium iodide (NaI)-supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28(-/-) mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28(-/-)IFN-γ(-/-) mice develop severe TEC H/P, and 2-3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4(+) T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40(-/-)IFN-γ(-/-)CD28(-/-) mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ(-/-)CD28(-/-) mice is a result of reduced regulatory T cell (Treg) numbers, as CD28(-/-) mice have significantly fewer Tregs, and transfer of CD28(+) Tregs inhibits TEC H/P. Essentially all female IFN-γ(-/-)CD28(-/-) NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems. PMID:27521344

  4. New Murine Model of Early Onset Autoimmune Thyroid Disease/Hypothyroidism and Autoimmune Exocrinopathy of the Salivary Gland.

    PubMed

    Kayes, Timothy Daniel; Weisman, Gary A; Camden, Jean M; Woods, Lucas T; Bredehoeft, Cole; Downey, Edward F; Cole, James; Braley-Mullen, Helen

    2016-09-15

    Sixty to seventy percent of IFN-γ(-/-) NOD.H-2h4 mice given sodium iodide (NaI)-supplemented water develop a slow onset autoimmune thyroid disease, characterized by thyrocyte epithelial cell (TEC) hyperplasia and proliferation (H/P). TEC H/P develops much earlier in CD28(-/-) mice and nearly 100% (both sexes) have severe TEC H/P at 4 mo of age. Without NaI supplementation, 50% of 5- to 6-mo-old CD28(-/-)IFN-γ(-/-) mice develop severe TEC H/P, and 2-3 wk of NaI is sufficient for optimal development of severe TEC H/P. Mice with severe TEC H/P are hypothyroid, and normalization of serum thyroxine levels does not reduce TEC H/P. Activated CD4(+) T cells are sufficient to transfer TEC H/P to SCID recipients. Thyroids of mice with TEC H/P have infiltrating T cells and expanded numbers of proliferating thyrocytes that highly express CD40. CD40 facilitates, but is not required for, development of severe TEC H/P, as CD40(-/-)IFN-γ(-/-)CD28(-/-) mice develop severe TEC H/P. Accelerated development of TEC H/P in IFN-γ(-/-)CD28(-/-) mice is a result of reduced regulatory T cell (Treg) numbers, as CD28(-/-) mice have significantly fewer Tregs, and transfer of CD28(+) Tregs inhibits TEC H/P. Essentially all female IFN-γ(-/-)CD28(-/-) NOD.H-2h4 mice have substantial lymphocytic infiltration of salivary glands and reduced salivary flow by 6 mo of age, thereby providing an excellent new model of autoimmune exocrinopathy of the salivary gland. This is one of very few models where autoimmune thyroid disease and hypothyroidism develop in most mice by 4 mo of age. This model will be useful for studying the effects of hypothyroidism on multiple organ systems.

  5. B cells in autoimmune diseases: Insights from analyses of immunoglobulin variable (Ig V) gene usage

    PubMed Central

    Foreman, Angela Lee; Van de Water, Judy; Gougeon, Marie-Lise; Gershwin, M. Eric

    2007-01-01

    The role of B cells in autoimmune diseases has not been fully elucidated. It is also unclear whether breaking of B cell tolerance in patients with autoimmune diseases is due to underlying defects in the molecular mechanisms involved in the arrangement of antibody genes or deficiencies in the subsequent selective influences that shape the antibody repertoire. Analysis of immunoglobulin (Ig) variable (V) gene usage is beginning to provide answers to some of these questions. Such analyses have identified some differences in the basic Ig V gene repertoire of patients with autoimmune diseases compared to healthy controls, even though none of these differences can be considered major. Defects in positive and negative selection, mutational targeting and, in some cases, receptor editing have also been detected. In addition, analysis of Ig V gene usage in target organs and tissues of patients with autoimmune diseases have clearly demonstrated that there is a highly compartmentalized clonal expansion of B cells driven by a limited number of antigens in these tissues. Great progress has been made in the structural and functional characterization of disease-associated antibodies, largely because of the development of the combinatorial library technique. Use of antibodies generated by this technique offers great promise in identifying B cell epitopes on known target antigens and in gaining greater insights into the pathogenic role of B cells in both B- and T-cell-mediated autoimmune diseases. PMID:17537385

  6. Managing antiretroviral-associated liver disease.

    PubMed

    Dieterich, Douglas

    2003-09-01

    The use of all potent drugs is associated with toxicities and antiretroviral (ARV) drugs are no exception. Antiretroviral therapy-associated hepatic toxicity is of increasing concern in the management of patients with HIV/AIDS. Liver toxicity has been reported in some HIV-infected patients being treated with drugs from all of these classes of ARV drugs: protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although the majority of cases involve asymptomatic elevations of liver enzymes (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]), severe, and, in a minority of cases, life threatening, liver disease has been reported in patients treated with ARV drugs. The exact causes of elevated plasma levels of AST and ALT are complex and, in many cases, obscure. The combination of viral hepatic disease, drugs that act adversely directly on the liver and drugs that act on other systems of the body which in turn, adversely affect the liver, can result in hepatic toxicity. Such toxicity may be inappropriately attributed solely to the direct effect of a drug. Knowledge of the possible causes of liver toxicity, and ways to avoid it, should reduce the risk of developing hepatotoxicity. The physician's task is to prevent the development of liver toxicity, e.g., by choosing appropriate therapeutic regimens and by careful management of the patient. This involves frequent monitoring of the patient, both clinically and by utilizing liver function tests on a regular basis. If signs and symptoms of liver disease do develop, prompt and expert management is essential. This review discusses the influence of a number of factors on hepatic toxicity including viral hepatitis, insulin resistance and the specific ARV drugs used in the treatment of patients with HIV/AIDS.

  7. An increase in tolerogenic dendritic cell and natural regulatory T cell numbers during experimental autoimmune encephalomyelitis in Rras-/- mice results in attenuated disease.

    PubMed

    Ray, Avijit; Basu, Sreemanti; Miller, Nichole M; Chan, Andrew M; Dittel, Bonnie N

    2014-06-01

    R-Ras is a member of the Ras superfamily of small GTPases, which are regulators of various cellular processes, including adhesion, survival, proliferation, trafficking, and cytokine production. R-Ras is expressed by immune cells and has been shown to modulate dendritic cell (DC) function in vitro and has been associated with liver autoimmunity. We used Rras-deficient mice to study the mechanism whereby R-Ras contributes to autoimmunity using experimental autoimmune encephalomyelitis (EAE), a mouse model of the CNS autoimmune disease multiple sclerosis. We found that a lack of R-Ras in peripheral immune cells resulted in attenuated EAE disease. Further investigation revealed that, during EAE, absence of R-Ras promoted the formation of MHC II(low) DC concomitant with a significant increase in proliferation of natural regulatory T cells, resulting in an increase in their cell numbers in the periphery. Our study suggests a novel role for R-Ras in promoting autoimmunity through negative regulation of natural regulatory T cell numbers by inhibiting the development of MHCII(low) DC with tolerogenic potential.

  8. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

    2015-08-01

    Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge. PMID:25842074

  9. Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

    PubMed

    Ramos-Casals, Manuel; Brito-Zerón, Pilar; Kostov, Belchin; Sisó-Almirall, Antoni; Bosch, Xavier; Buss, David; Trilla, Antoni; Stone, John H; Khamashta, Munther A; Shoenfeld, Yehuda

    2015-08-01

    Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge.

  10. Exercise as a therapeutic tool to counteract inflammation and clinical symptoms in autoimmune rheumatic diseases.

    PubMed

    Perandini, Luiz Augusto; de Sá-Pinto, Ana Lúcia; Roschel, Hamilton; Benatti, Fabiana Braga; Lima, Fernanda Rodrigues; Bonfá, Eloisa; Gualano, Bruno

    2012-12-01

    Chronic inflammation is a common feature shared by several autoimmune rheumatic diseases, such as rheumatoid arthritis, systemic lupus erythematosus, idiopathic inflammatory myopathies, systemic sclerosis, and ankylosing spondylitis. Therefore, blocking or reducing inflammation is one of the major treatment strategies in these diseases. In this context, exercise training has emerged as a potential therapeutic tool in counteracting systemic inflammation, thereby leading to better clinical outcomes. The aims of this review are i) to provide a summary of the clinical effects of exercise training in selected autoimmune rheumatic diseases; and ii) to discuss the potential anti-inflammatory role of exercise training in autoimmune rheumatic diseases, stressing the gaps in literature and the clinical and scientific perspectives in the field.

  11. Little peptide, big effects: the role of LL-37 in inflammation and autoimmune disease.

    PubMed

    Kahlenberg, J Michelle; Kaplan, Mariana J

    2013-11-15

    The innate immune system utilizes many approaches for defense against invading microorganisms, including complement-mediated lysis, engulfment, formation of neutrophil extracellular traps, and release of antimicrobial peptides. Although classically thought to be driven by adaptive immunity, the development of autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus is increasingly associated with dysregulated innate immune pathways. An emerging theme within this literature is the contribution of antimicrobial peptides to the development of autoimmune disorders. This is best exemplified in atopic dermatitis and psoriasis where the defensins and the single human cathelicidin, LL-37, may contribute to disease. Furthermore, in the past few years, a role for LL-37 has emerged in the pathogenesis of systemic lupus erythematosus, rheumatoid arthritis, atherosclerosis, and possibly other diseases. In this review, we discuss the role of LL-37 and its murine ortholog, mCRAMP, in the modulation of immune and inflammatory pathways and their effects on autoimmune and inflammatory diseases.

  12. The Postnatal Maternal Environment Affects Autoimmune Disease Susceptibility in A/J mice

    PubMed Central

    Case, Laure K.; Rio, Roxana del; Bonney, Elizabeth A.; Zachary, James F.; Blankenhorn, Elizabeth P.; Tung, Kenneth S. K.; Teuscher, Cory

    2009-01-01

    The postnatal maternal environment is known to increase susceptibility to a number of autoimmune diseases. Here we asked whether the postnatal maternal environment could influence autoimmune disease development to day 3 thymectomy (d3tx)-induced autoimmune ovarian disease (AOD) and experimental allergic encephalomyelitis (EAE) in cross-fostered A/J and B6 mice. A/J pups foster-nursed by B6 mothers exhibit an increase in autoimmune disease development while cross-fostering B6 pups on A/J mothers did not alter their susceptibility. The increase in AOD incidence seen in foster-nursed d3tx A/J mice correlated with a decrease in the total number of CD4+ T cells in the lymph nodes of these animals. Analysis of the cellular composition in the milk revealed that B6 mice shed significantly more maternally derived lymphocytes into their milk compared to A/J mothers. These data suggest that there are maternally derived postnatal factors that influence the development of autoimmune disease in A/J mice. PMID:19914609

  13. [Nonalcoholic fatty liver disease in children].

    PubMed

    Bojórquez-Ramos, María del Carmen

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in children and adolescents in the United States of America (USA) and probably in the entire western hemisphere, due to the increase in the prevalence of overweight and obesity. Steatosis can progress to inflammation, fibrosis and even cirrhosis, which increases the morbidity and mortality associated to liver disease. In every overweight and obese child a thorough analysis should be performed including liver function tests and liver ultrasound, in order to establish a timely diagnosis. The liver biopsy is the most specific study to rule out other potentially treatable entities. It is necessary to count on non-invasive methods to detect children with NAFLD and identify those in risk of progression. Biomarkers related to inflammation, oxidative stress, apoptosis and fibrosis have been reported. The main goal of the treatment is to modify the life style, starting with a healthy diet and an increase of physical activity. Regarding pharmacological treatment, there is evidence of histological improvement with vitamin E use, as opposed to metformin, but more conclusive studies regarding this subject are needed.

  14. Nonmedicinal interventions in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Nanau, Radu M; Cohen, Lawrence B

    2015-01-01

    Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular injury such as hepatocyte ballooning. NASH is a distinct entity from NAFLD, and is characterized by the presence of inflammation with hepatocytes damage, with or without fibrosis. While several therapeutic strategies have been proposed to improve this condition, the present review aims to discuss nonmedicinal interventions used to reduce liver involvement or to prevent the disease altogether. The authors investigated dietary patterns and vitamin deficiencies associated with NAFLD, and their role in enhancing disease severity. Additionally, they reviewed the role of exercise and the use of interventions, such as as intragastric balloon and bariatric surgery, for improving disease progression. The authors propose monitoring disease progression or repair by following changes in cytoadipokine levels. PMID:26076224

  15. Autoantibodies with Enzymatic Properties in Human Autoimmune Diseases

    PubMed Central

    Wootla, Bharath; Lacroix-Desmazes, Sébastien; Warrington, Arthur E.; Bieber, Allan J.; Kaveri, Srini V.; Rodriguez, Moses

    2011-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. In addition to this plethora of functions, some antibodies express enzymatic activity. Antibodies endowed with enzymatic properties have been described in human autoimmune manifestations for more than a decade in a variety of disorders such as autoimmune thyroiditis, systemic erythematosus (SLE), scleroderma, rheumatoid arthritis (RA), multiple sclerosis (MS) and acquired hemophilia (AH). Antibodies isolated from these conditions were able to specifically hydrolyze thyroglobulin, DNA, RNA, myelin basic protein (MBP), and factor VIII (FVIII) or factor IX (FIX), respectively. The therapeutic relevance of these findings is discussed. PMID:21624820

  16. Human adjuvant disease: remission of silicone induced autoimmune disease after explanation of breast augmentation.

    PubMed Central

    kaiser, W; Biesenbach, G; Stuby, U; Grafinger, P; Zazgornik, J

    1990-01-01

    Autoimmune diseases following silicone or paraffin implantation are rarely encountered complications of plastic surgery. A 42 year old woman is presented who developed clinical and immunological features of systemic lupus erythematosus 11 years after silicone augmentation. After explanation antinuclear antibody titres decreased from 1/1280 to 1/160, C4 complement fraction and the previously raised angiotensin converting enzyme normalised in step with clinical improvement. It is important that plastic surgeons and rheumatologists should be aware of this possible association. PMID:2256743

  17. Diagnosis and Management of Alcoholic Liver Disease

    PubMed Central

    Dugum, Mohannad; McCullough, Arthur

    2015-01-01

    Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with m