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1

Anti-dsDNA antibodies and disease classification in antinuclear antibody positive patients: the role of analytical diversity  

PubMed Central

Background: The presence of "anti-DNA antibodies in abnormal titres" is a well established criterion for SLE classification, but there is no agreement on the performance of this test. Objective: To study the correlation between clinical findings and five different solid and solution phase anti-DNA antibody assays. Methods: 158 consecutively collected ANA positive sera were studied in a double blind fashion. Anti-DNA antibodies were determined by different solid phase assays (ssDNA-, dsDNA- specific ELISA, EliA anti-dsDNA assay, Crithidia luciliae assay), and by an experimental solution phase anti-DNA assay using biotinylated pUC18 plasmid, human, calf thymus, and E coli DNA. Antibody affinity was determined by surface plasmon resonance. Clinical data were obtained independently of the laboratory analyses and later related to the anti-dsDNA findings. Results: Anti-dsDNA antibodies were most frequently detected by ELISA, but were not specific for SLE as they were present in up to 30% of other disease groups. Those detected by the Crithidia luciliae assay were predictive for SLE, while antibodies binding in solution phase ELISA using the pUC18 correlated strongly with the Crithidia luciliae assay. Surface plasmon resonance analysis showed that antibody binding to pUC18 was not due to higher relative affinity for dsDNA in general, but apparently to specificity for that plasmid DNA. Serum samples from three patients with lupus nephritis were positive in both pUC18 solution phase and Crithidia luciliae assays. Conclusions: Assay principle selection is decisive for the detection of clinically significant anti-DNA antibodies. Revision of the anti-DNA antibody criterion in the SLE classification may be needed. PMID:15020332

Haugbro, K; Nossent, J; Winkler, T; Figenschau, Y; Rekvig, O

2004-01-01

2

Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies.  

PubMed

Treatment of patients with lupus-associated thrombocytopenia (SLE-ITP) is not standardized. We report data on efficacy and safety of hydroxychloroquine (HCQ) in this setting and in ITP patients with positive antinuclear antibodies (ANA) without definite SLE. Inclusion criteria were: definite diagnosis of ITP with a platelet count (PLT) <50 × 10(9) /L, ANA ? 1/160 on Hep2 cells with or without a definite diagnosis of SLE, and no sustained response to at least one previous treatment-line and treatment with HCQ. Response criteria were Complete Response (CR) for PLT ? 100 × 10(9) /L and Response (R) for PLT ?30 × 10(9) /L and at least twice the initial value. Forty patients (32 females) with a mean age of 35 ± 17 years and PLT at ITP diagnosis of 14 ± 13 × 10(9) /L were analyzed. Twelve (30%) patients had a SLE-ITP, 28 patients had only positive ANA. All the patients failed to respond to oral prednisone with a median of two treatment-lines (1-5) before HCQ which was initially given in combination with another ITP treatment in 36 patients. Overall response rate was 60% (24/40) including 18 lasting CR and six lasting R maintained with a median follow-up of 64 months (6-146), in ¾ of cases with only HCQ and no concomitant ITP treatment. The response rate (CR+R) was higher in the SLE group vs ANA-positive group (83% vs 50%, P < 0.05). No patient stopped HCQ because of a side-effect. HCQ appears to be a safe and effective second line treatment for patients with SLE-ITP or ITP and high titer of ANA. This trial was registered at www.clinicaltrials.gov as # NCT01549184. PMID:24254965

Khellaf, Mehdi; Chabrol, Amèlie; Mahevas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

2014-02-01

3

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2012 CFR

...antibody immunological test system. 866.5100 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5100 Antinuclear...antibody immunological test system is a device that consists...antibodies in serum, other body fluids,...

2012-04-01

4

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2010 CFR

...antibody immunological test system. 866.5100 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5100 Antinuclear...antibody immunological test system is a device that consists...antibodies in serum, other body fluids,...

2010-04-01

5

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2011 CFR

...antibody immunological test system. 866.5100 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5100 Antinuclear...antibody immunological test system is a device that consists...antibodies in serum, other body fluids,...

2011-04-01

6

The Prevalence of Antinuclear Antibodies in Patients with Sarcoidosis  

PubMed Central

Introduction. Sarcoidosis, which is a chronic inflammatory granulomatous disease, can mimic different rheumatologic diseases including connective tissue diseases. Antinuclear antibodies are the markers used for connective tissue diseases. Aim. To determine antinuclear antibody frequency and any possible correlation with clinical and laboratory data in sarcoidosis patients. Material and Method. Forty-two sarcoidosis patients, 45 rheumatoid arthritis patients, and 45 healthy volunteers who were followed up in rheumatology outpatient clinic were included in this study. Demographic, clinical, serological, and radiological data of all patients were recorded. Antinuclear antibodies were determined with indirect immunofluorescent method and 1/100 titration was accepted as positive. The cases that were ANA positive were evaluated with immunoblot method. Results. Average age of the 42 patients (10 males) with sarcoidosis was 45.2 (20–70 years), and average disease duration was 3.5 years. ANA positivity was detected in 12 (28.5%) patients with sarcoidosis (1/100 in 10 patients, 1/320 in two patients), in 19 of RA patients (42.2%), and in two of healthy volunteers in low titer (P < 0.001). In the subgroup analysis made by immunblot test, one patient had anticentromere antibody, one had anti-Ro antibody, one had anti-Scl-70 antibody, one had anti-dsDNA antibody, and eight patients were negative. The two patients who had anticentromere and anti-Scl-70 antibodies had also Sjögren's syndrome and scleroderma diagnosis, respectively. Discussion. The prevalence of ANA in patients with sarcoidosis was found to be significantly higher than healthy control group and lower than RA patients. This result shows that ANA may have an important role in the pathogenesis of sarcoidosis and also could be important in revealing the overlap syndromes of sarcoidosis-connective tissue diseases. Further studies with larger series are necessary in this subject. PMID:25580285

Kobak, Senol; Yilmaz, Hatice; Sever, Fidan; Duran, Arzu; Sen, Nazime; Karaarslan, Ahmet

2014-01-01

7

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2013 CFR

...antibody immunological test system. 866.5100 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5100 Antinuclear...antibody immunological test system is a device that consists...antibodies in serum, other body fluids, and...

2013-04-01

8

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

...antibody immunological test system. 866.5100 Section...DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Immunological Test Systems § 866.5100 Antinuclear...antibody immunological test system is a device that consists...antibodies in serum, other body fluids, and...

2014-04-01

9

Development of positive antinuclear antibodies and rheumatoid factor in systemic juvenile idiopathic arthritis points toward an autoimmune phenotype later in the disease course  

PubMed Central

Background Systemic juvenile idiopathic arthritis (sJIA) is commonly considered an autoinflammatory disease. However, sJIA patients may develop aggressive arthritis without systemic inflammation later in the disease, resembling an autoimmune phenotype similar to other subtypes of JIA. The objective of this study was to determine whether antinuclear antibodies (ANA) and rheumatoid factor (RF) will develop in patients with sJIA over the course of the disease. Findings A single center sample of sJIA patients with follow-up of more than one year was obtained. A retrospective chart survey was used to extract demographic and clinical data as well as presence and titers of ANA and RF at diagnosis and during follow-up. 32 patients were included in the study, with a median age of 4.2 years and median follow-up of 6.0 years. 8/32 patients had ANA titers???1:80 at diagnosis, with 22/32 patients showing rising ANA titers with titers???1:80 at last follow-up (p =0.001). 10/32 patients had a positive RF at least once during follow-up, compared to 0/32 at diagnosis (p?=?0.001). In 5/10 patients, positive RF was documented at least twice, more than twelve weeks apart. Patients treated with TNF antagonists were not significantly more likely to develop positive ANA titers (p?=?0.425) or positive RF (p?=?0.703). Conclusions Patients with sJIA developed increased ANA titers and positive RF over the course of the disease, independent of treatment with TNF antagonists. This might point towards an autoimmune, rather than an autoinflammatory phenotype later in the course of sJIA. PMID:25114627

2014-01-01

10

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage  

PubMed Central

Background: Antinuclear antibodies (ANAs) in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. Objective: In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. Materials and Methods: 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. Results: ANAs were detected in 74 of 560 (13.21%) patient with recurrent miscarriage, and in only 5 of 560 (0.9%) controls (p<0.001). ANA positivity was generally found with low-positive results (1.40-1.80) in about 38% of positive cases, whereas moderate titres (1.160-1.320) and high titres (>1.640) were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Conclusion: Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients. PMID:24799884

Molazadeh, Morteza; Karimzadeh, Hadi; Azizi, Mohammad R

2014-01-01

11

Occurrence, immunoglobulin pattern and specificity of antinuclear antibodies in sera of procaine amide treated patients  

PubMed Central

Thirty-one out of fifty patients receiving procaine amide were found to develop antinuclear antibodies belonging in most cases to the IgM and IgG classes and to a lesser extent to the IgA class. Specific interaction between these antibodies and a nucleoprotein component could be demonstrated in a large proportion of cases. No relation was found between occurrence of antinuclear antibodies and development of an immune response to procaine amide itself. PMID:4099667

Klajman, A.; Camin-Belsky, N.; Kimchi, A.; Ben-Efraim, S.

1970-01-01

12

Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies  

SciTech Connect

The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases.

Holers, V.M.; Kotzin, B.L.

1985-09-01

13

Antinuclear Antibodies as Potential Markers of Lung Cancer1 Felix Fernandez-Madrid,2  

E-print Network

Antinuclear Antibodies as Potential Markers of Lung Cancer1 Fe´lix Ferna´ndez-Madrid,2 Pamela J of ANAs in lung cancer. We have previously reported that autoantibodies to collagen antigens resembling those found in the connective tissue diseases are consistently detected in the sera from lung cancer

VandeVord, Pamela

14

The Prevalence of Antinuclear Antibodies in the General Population of China: A Cross-Sectional Study  

PubMed Central

Background The incidence of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and primary biliary cirrhosis has increased significantly in China. Information about the susceptibility or potential of autoimmune diseases in the general population is lacking. Objective To explore the prevalence of antinuclear antibody (ANA) and its specificities in the general population in China. Methods Twenty thousand nine hundred seventy sera samples were taken from the physical examination center in Baoding, China. Indirect immunofluorescence and line immunoassays were used to detect ANA and its specificities, respectively. Results Samples from females had a higher prevalence of ANA than samples from males (?2 = 278.55; P < 0.01). For both sexes, the prevalence of ANA positively correlated with age and there were significant differences among different age groups at 10-year intervals, except the 80 years group (P < 0.05). One thousand two hundred forty-three ANA-positive samples were further analyzed with line immunoassays. There was a significant difference among age groups and between sex groups in terms of the specific autoantibodies (P < 0.01). The autoantibodies with the top-3 positive frequencies were anti-Ro-52, anti-M2, and anti-SSA. Conclusions There was a high prevalence of ANA positivity in the general Chinese population that seemed to be influenced by sex and age and correlated with specific autoantibodies. PMID:25473438

Guo, Ya-Ping; Wang, Chun-Guang; Liu, Xin; Huang, Yi-Qian; Guo, De-Li; Jing, Xing-Zhuo; Yuan, Chun-Gang; Yang, Song; Liu, Jin-Mei; Han, Meng-Si; Li, Hong-Xing

2014-01-01

15

Antinuclear antibodies and the diagnosis of systemic lupus erythematosus in patients with acute intermittent porphyria.  

PubMed Central

To investigate the previously postulated association of systemic lupus erythematosus (SLE) and porphyria 38 patients with various types of porphyria were investigated for clinical and laboratory evidence of a connective tissue disease. Antinuclear antibodies (ANAs) were found in 8/15 (53%) patients with acute intermittent porphyria. These patients were more likely to have had a recent acute attack of porphyria, but only one patient had clinical evidence of SLE. Antinuclear antibodies were not found in any patients with latent acute intermittent porphyria or appreciably in any of the other types of porphyria studied. This finding of ANAs in patients with acute intermittent porphyria may explain the previously described association with SLE. Strict diagnostic criteria need to be used in any one patient as these two disorders have many similar clinical manifestations. PMID:2339906

Allard, S A; Charles, P J; Herrick, A L; McColl, K E; Scott, J T

1990-01-01

16

Elevated antinuclear antibodies and altered anti-Epstein-Barr virus immune responses.  

PubMed

It has been shown that Epstein-Barr virus (EBV) is able to alter the immune response towards self-antigens and may enhance risk of autoimmune diseases such as systemic lupus erythematosus (SLE) in genetically predisposed individuals. In this study, we evaluated the specific antibody immune response against EBV in patients with anti-nuclear autoantibodies (ANA) in comparison with ANA-negative healthy controls. For this purpose, 92 patients with an high anti-ANA reactivity with or without concomitant extractable nuclear antigen (ENA) or double stranded DNA (dsDNA) positivity were selected and compared with 146 healthy donors. We found that anti-EBV-VCA and EA IgG concentrations were significantly higher in ANA-positive patients in comparison to the controls (VCA P<0.0001 and EA P<0,03) as well as in those ANA-positive patients that showed a concomitant ENA positivity (P=0.0002). Interestingly, elevated anti-EBNA-1 IgG was found in a group of patients who had anti SSA/Ro antibodies. Anti-VCA IgM Abs were more frequently found in those patients with a very high titer of ANA (P=0.06); moreover detection of anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in the patient than in the control group. Both these conditions correlate with a recent EBV infection or reactivation. The data suggest that EBV, particularly during acute infection or in its reactivation phase, could be involved in the ANA and ENA autoantibody formation. PMID:25300805

Cuomo, Laura; Cirone, Mara; Di Gregorio, Ana Oliva; Vitillo, Marina; Cattivelli, Marina; Magliocca, Vittoria; Maiorano, Silvana; Meledandri, Marcello; Scagnolari, Carolina; La Rocca, Sebastiano; Trivedi, Pankaj

2015-01-01

17

Disseminated tuberculosis in a patient with antinuclear antibody-negative systemic lupus erythematosus: a rare association  

PubMed Central

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse manifestations. Tuberculosis is known to induce and exacerbate SLE and it becomes quite difficult to diagnose tuberculosis in this setting, owing to a similar, overlapping presentation of tuberculosis and SLE. We report a case of disseminated tuberculosis in a patient with antinuclear antibody-negative SLE. Treatment was started with antitubercular drugs together with hydroxychloroquine and steroid. After 6?months of follow-up the patient recovered with treatment. PMID:23365171

Kumar, Naveen; Aggarwal, Puneet; Dev, Nishanth; Kumar, Gunjan

2013-01-01

18

Determination of Anti-nuclear Antibody Pattern Distribution and Clinical Relationship  

PubMed Central

Background and Objectives: Autoantibodies are immunglobulins occurred directly against autoantigens that are known as endogen antigens. Autoimmune disease is an occasion that the body begins a fight against its own cells and tissues. The antibodies that are created by the body against its own cell nuclei are called as anti-nuclear antibodies (ANA), and one of the methods used for detection and pattern of ANA is indirect immunofluorescence test (IIF). In the present study, it was aimed to determine the rate of ANA positivity and patterns of the positive specimens, and to investigate the relationship between ANA positivity and diseases in patients. Methods: ANA test results of a total of 3127 patients admitted during March 2010 to December 2012 were evaluated retrospectively. ANA test (HEp 20-10, EUROIMMUN, Germany) was used in dilution of 1:100 in IIF test. Results: A total of 494 (15.8%) resulted as ANA positive. ANA positivity rate was significantly higher in female patients than the male ones (p<0.001). The most frequent ANA patterns were coarse speckled pattern (154 patients, 31.2%), nucleolar pattern (89 patients, 18.0%), fine speckled pattern (57 patients, 11.5%), and speckled pattern (48 patients, 9.7%). ANA positivity was most commonly determined in rheumatoid arthritis (RA) (42 patients, 8.5%), systemic lupus erythematosus (SLE) (29 patients, 5.9%), and rheumatoid vasculitis (RV) (28 patients, 5.7%). The most frequent symptoms or findings were joint pain (127 patients, 26.0%) and anemia (28 patients, 5.7%). ANA positivity rates were found to be significantly higher in patients with RA (p<0.001), with SLE (p<0.001), and with Raynaud phenomenon (p=0.001) in comparison to the controls. Amongst the most frequent diseases evaluated, no significant differences were found between the control groups and the groups of RV (p=0.089), multiple sclerosis (p=0.374), and Sjögren syndrome (p=0.311) in terms of ANA positivity rates. Conclusions: The present study is the first study reporting the positivity rate and distribution of ANA in Bolu located in northwestern Turkey. Information about the pattern types and the distribution of the patterns according to the diseases and symptoms contribute in diagnosis of autoimmune diseases. It is observed that clinical diagnosis has been supported significantly by ANA test according to data of our study. PMID:24772147

Mengeloglu, Zafer; Tas, Tekin; Kocoglu, Esra; Aktas, Gülali; Karabörk, Seyda

2014-01-01

19

Anti-nuclear antibody screening using HEp-2 cells.  

PubMed

The American College of Rheumatology position statement on ANA testing stipulates the use of IIF as the gold standard method for ANA screening(1). Although IIF is an excellent screening test in expert hands, the technical difficulties of processing and reading IIF slides--such as the labor intensive slide processing, manual reading, the need for experienced, trained technologists and the use of dark room--make the IIF method difficult to fit in the workflow of modern, automated laboratories. The first and crucial step towards high quality ANA screening is careful slide processing. This procedure is labor intensive, and requires full understanding of the process, as well as attention to details and experience. Slide reading is performed by fluorescent microscopy in dark rooms, and is done by trained technologists who are familiar with the various patterns, in the context of cell cycle and the morphology of interphase and dividing cells. Provided that IIF is the first line screening tool for SARD, understanding the steps to correctly perform this technique is critical. Recently, digital imaging systems have been developed for the automated reading of IIF slides. These systems, such as the NOVA View Automated Fluorescent Microscope, are designed to streamline the routine IIF workflow. NOVA View acquires and stores high resolution digital images of the wells, thereby separating image acquisition from interpretation; images are viewed an interpreted on high resolution computer monitors. It stores images for future reference and supports the operator's interpretation by providing fluorescent light intensity data on the images. It also preliminarily categorizes results as positive or negative, and provides pattern recognition for positive samples. In summary, it eliminates the need for darkroom, and automates and streamlines the IIF reading/interpretation workflow. Most importantly, it increases consistency between readers and readings. Moreover, with the use of barcoded slides, transcription errors are eliminated by providing sample traceability and positive patient identification. This results in increased patient data integrity and safety. The overall goal of this video is to demonstrate the IIF procedure, including slide processing, identification of common IIF patterns, and the introduction of new advancements to simplify and harmonize this technique. PMID:24998977

Buchner, Carol; Bryant, Cassandra; Eslami, Anna; Lakos, Gabriella

2014-01-01

20

Longitudinal study of antinuclear and anticardiolipin antibodies in pregnant women with systemic lupus erythematosus and antiphospholipid syndrome  

Microsoft Academic Search

The objective of this study was to perform a longitudinal follow-up of antinuclear antibodies (ANAs) and anticardiolipin antibodies titers (aCL) throughout pregnancy in a group of patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients during their therapy for the prevention of fetal loss and to examine their relationship with pregnancy outcome. Thirty patients and 15 controls were

Mario Salazar-Páramo; Luis J. Jara; Azucena Ramos; Leonor Barile; Guadalupe Machado; Ignacio García-De La Torre

2002-01-01

21

DIAGNOSTIC VALUE OF ANTI-RA33 ANTIBODY, ANTIKERATIN ANTIBODY, ANTIPERINUCLEAR FACTOR AND ANTINUCLEAR ANTIBODY IN EARLY RHEUMATOID ARTHRITIS: COMPARISON WITH RHEUMATOID FACTOR  

Microsoft Academic Search

SUMMARY The goal of this prospective longitudinal study was to determine the serological profile of early rheumatoid arthritis (RA), and to test whether antikeratin antibody (AKA), antiperinuclear factor (API7), anti-RA33 antibody and antinuclear antibodies (ANA) had an additional diagnostic value when prescribed after rheumatoid factor (RF)-detecting methods. Sixty-nine patients with early polyarthritis suggestive of RA, seen between 1991 and 1993,

C. CORDONNIER; O. MEYER; E. PALAZZO; M. DE BANDT; A. ELIAS; P. NICAISE; T. HAÏM; M. F. KAHN; G. CHATELLIER

1996-01-01

22

Anti-nuclear antibodies as predictor of outcome in a multi-center cohort of Italian children and adolescents with Raynaud's phenomenon.  

PubMed

A retrospective multi-center data collection of clinical, laboratory, and treatment characteristics of 94 Caucasian children and adolescents with Raynaud's phenomenon (RP) started at a mean age of 12.8?±?5 years, with variable involvement of hands, feet, and face, was performed for a period of 3 years. Collected data included nailfold videocapillaroscopy (NVC), lung function tests, and different laboratory tests finalized to characterize an eventual connective tissue disease (CTD), disclosed by RP itself. Twelve patients presented an early-scleroderma pattern at NVC, 1 a late-scleroderma pattern, and 58 a nonspecific pattern. Laboratory data results showed the positivity of anti-nuclear antibodies (ANA) in 29 % of patients. After this 3-year period of observation, 8 patients had developed a CTD. Our data examined by multivariate analysis, though limited to a multi-center cohort of pediatric patients with RP, strongly suggest that ANA positivity is a significant predictor of progression of RP towards a CTD. PMID:25428518

Falcini, Fernanda; Rigante, Donato; Candelli, Marcello; Martini, Giorgia; Corona, Fabrizia; Petaccia, Antonella; La Torre, Francesco; Raffaele, Carmela G L; Matucci Cerinic, Marco

2015-01-01

23

Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register  

PubMed Central

Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes. Design Observational cohort study. Setting One university hospital rheumatology unit in Sweden. Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ?4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ?2 typical organ manifestations at the time of diagnosis (Fries’ criteria). Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique). Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage. Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage. PMID:24163206

Frodlund, Martina; Dahlström, Örjan; Kastbom, Alf; Skogh, Thomas; Sjöwall, Christopher

2013-01-01

24

Induction of Antinuclear Antibodies by De Novo Autoimmune Hepatitis Regulates Alloimmune Responses in Rat Liver Transplantation  

PubMed Central

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation. PMID:24454474

Nakano, Toshiaki; Goto, Shigeru; Lai, Chia-Yun; Hsu, Li-Wen; Tseng, Hui-Peng; Chen, Kuang-Den; Wang, Chih-Chi; Cheng, Yu-Fan; Chen, Chao-Long

2013-01-01

25

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-} mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE{sup -/-} mice.

Wang, Yuehai [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Huang, Ziyang, E-mail: huangziyang666@126.com [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Lu, Huixia [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Huili; Wang, Zhenhua [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Chen, Xiaoqing [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Ouyang, Qiufang [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Tang, Mengxiong; Hao, Panpan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Ni, Jingqin [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Xu, Dongming [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Zhang, Mingxiang; Zhang, Qunye [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Ling [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); and others

2012-07-13

26

Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies  

PubMed Central

The detection of autoantibodies that target intracellular antigens, commonly termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). Different methods are available for detection of ANA and all bearing their own advantages and limitations. Most laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell substrates. Due to the subjectivity of this diagnostic platform, automated digital reading systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges. PMID:24868563

Mahler, Michael; Meroni, Pier-Luigi; Bossuyt, Xavier; Fritzler, Marvin J.

2014-01-01

27

Anti-Nuclear Antibody Production and Autoimmunity in Transgenic Mice that Over-Express the Transcription Factor Bright  

PubMed Central

The B cell-restricted transcription factor, Bright, up-regulates immunoglobulin heavy chain transcription three- to seven-fold in activated B cells in vitro. Bright function is dependent upon both active Bruton’s tyrosine kinase and its substrate, the transcription factor, TFII-I. In mouse and human B lymphocytes, Bright transcription is down regulated in mature B cells, and its expression is tightly regulated during B cell differentiation. To determine how Bright expression affects B cell development, transgenic mice were generated that express Bright constitutively in all B lineage cells. These mice exhibited increases in total B220+ B lymphocyte lineage cells in the bone marrow, but the relative percentages of the individual subpopulations were not altered. Splenic immature transitional B cells were significantly expanded both in total cell numbers and as increased percentages of cells relative to other B cell subpopulations. Serum immunoglobulin levels, particularly IgG isotypes, were increased slightly in the Bright transgenic mice compared to littermate controls. However, immunization studies suggest that responses to all foreign antigens were not increased globally. Moreover, four week-old Bright transgenic mice produced anti-nuclear antibodies. Older animals developed antibody deposits in the kidney glomeruli, but did not succumb to further autoimmune sequelae. These data indicate that enhanced Bright expression results in failure to maintain B cell tolerance and suggest a previously unappreciated role for Bright regulation in immature B cells. Bright is the first B cell-restricted transcription factor demonstrated to induce autoimmunity. Therefore, the Bright transgenics provide a novel model system for future analyses of B cell autoreactivity. PMID:17312145

Shankar, Malini; Nixon, Jamee C.; Maier, Shannon; Workman, Jennifer; Farris, A. Darise; Webb, Carol F.

2009-01-01

28

ANA (Antinuclear Antibody Test)  

MedlinePLUS

... is to perform additional testing for the autoantibodies Smith and ds-DNA, which, if possitive, would confirm ... Rheumatoid Arthritis , Sjögren Syndrome , Scleroderma Elsewhere On The Web Lupus Foundation of America American College of Rheumatology: ...

29

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: a cross-sectional study.  

PubMed

Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of auto-antibodies directed at antigens located in the nucleus (antinuclear auto-antibodies, or ANA) or the nucleolus (antinucleolar auto-antibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socio-economic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations. PMID:20176347

Gardner, Renee M; Nyland, Jennifer F; Silva, Ines A; Ventura, Ana Maria; de Souza, Jose Maria; Silbergeld, Ellen K

2010-05-01

30

Lactic dehydrogenase virus infection prevents development of anti-nuclear antibody in (NZB x NZW)F1 mice; role of prostaglandin E2 and macrophage Ia antigen expression.  

PubMed Central

Persistent lactic dehydrogenase virus (LDV) infection prevents the development of antinuclear antibody (ANA) in (NZB x NZW)F1 mice. To assess the suppressive mechanisms, we focused on the role of the E series of prostaglandin(PGE), since previously we have shown enhanced production of PGE by macrophages from chronically LDV-infected mice. Treatment with PGE2 suppressed ANA titres more markedly in non-infected mice than in LDV-infected mice. Indomethacin enhanced ANA titres more markedly in LDV-infected mice than in non-infected mice. The number of Ia antigen positive(Ia+) macrophages was less in LDV-infected mice than in uninfected mice. The number of Ia+ macrophages was decreased in non-infected mice by PGE2 treatment and increased in LDV-infected mice by indomethacin treatment. These results suggest that the low ANA production in LDV-infected (NZB x NZW)F1 mice may be related to the decreased number of Ia+ macrophages and that one of the factors responsible for suppression of Ia+ macrophages may be the enhanced PGE2 production in the LDV-infected mice. Images Fig. 6 PMID:1419777

Hayashi, T.; Mori, I.; Yamamoto, H.

1992-01-01

31

Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders  

PubMed Central

Objective: To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies. Methods: Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells. Results: Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack. Conclusions: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies. PMID:24415568

Sato, Douglas Kazutoshi; Callegaro, Dagoberto; Lana-Peixoto, Marco Aurelio; Waters, Patrick J.; Jorge, Frederico M. de Haidar; Takahashi, Toshiyuki; Nakashima, Ichiro; Apostolos-Pereira, Samira Luisa; Talim, Natalia; Simm, Renata Faria; Lino, Angelina Maria Martins; Misu, Tatsuro; Leite, Maria Isabel; Aoki, Masashi

2014-01-01

32

Anti-nuclear fantasies  

Microsoft Academic Search

The author critiques two recent anti-nuclear books - Indefensible Weapons by two American professors, Robert Jay Lifton and Richard Falk; and Beyond the Cold War, a collection of polemical essays by E.P. Thompson, British Marxist historian. He sees a common thread in these books of moral rejection of traditional Western policies more than a rejection of the weapons themselves. Western

1983-01-01

33

Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water  

SciTech Connect

Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects with 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers > 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r{sup 2} = .0205 in women and this correlation was almost statistically significant in men cc = .1282, r{sup 2} = .0253. In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erthematosus as perceived by the ARA score and the increased FANA titers.

Kilburn, K.H.; Warshaw, R.H. (Univ. of Southern California, Los Angeles (United States))

1992-02-01

34

Suppression of development of anti-nuclear antibody and glomerulonephritis in NZB x NZWF1 mice by persistent infection with lactic dehydrogenase virus: possible involvement of superoxide anion as a progressive effector.  

PubMed Central

The development of anti-nuclear antibody (ANA) and glomerulonephritis (GN) in autoimmune NZB x NZWF1 mice was suppressed by persistent lactic dehydrogenase virus (LDV) infection. This observation was used to study a possible pathogenetic role for the toxic oxygen radical, superoxide anion (O2-), in the progression of ANA and GN. Compared to macrophages from NZB x NZWF1 mice with LDV infection, macrophages from uninfected NZB x NZWF1 mice exhibited an age-related and drastic increase in O2- production in association with the development of the ANA and GN (representing the late stage of disease). NZB x NZWF1 mice with or without LDV infection were then given the O2- scavenger superoxide dismutase (SOD) during the late stage of the disease. Treatment of uninfected NZB x NZWF1 mice with SOD (10,000 units/mouse/day for 3 weeks) protected animals from the development of ANA and GN. SOD treatment also suppressed the development of the lesions in NZB x NZWF1 mice with LDV infection. Our findings suggest that O2- may, at least in part, contribute to the development of ANA and GN in the late stage of disease, and that decreased O2- production in NZB x NZWF1 mice with LDV infection may be responsible for the suppression of the development of ANA and GN in the late stage of the disease. Images Figure 7 Figure 9 PMID:8292553

Hayashi, T.; Noguchi, Y.; Kameyama, Y.

1993-01-01

35

Immunopathologic Studies of Systemic Lupus Erythematosus (SLE). I. Tissue-bound Immunoglobulins in Relation to Serum Antinuclear Immunoglobulins in Systemic Lupus and in Chronic Liver Disease with LE Cell Factor *  

PubMed Central

We studied the composition of tissue-bound immunoglobulins and of antinuclear factors by immunofluorescent techniques in five patients with systemic lupus and two with chronic liver disease associated with positive LE cell tests. Renal glomeruli in all seven demonstrated deposits of bound ?G-globulin and complement, although the presence of ?A- and ?M-immunoglobulins was variable. Blood vessel walls contained primarily ?G-globulin and complement in the systemic lupus patients, but such deposits were absent from vessels in the two with chronic liver disease. We observed antinuclear factors, demonstrated by immunofluorescence, in all three immunoglobulin classes. In six of the seven patients, evidence was obtained of a correspondence between the classes of bound immunoglobulins in glomeruli and vessels and the serum titers of antinuclear immunoglobulins. These observations are consistent with the concept that immunoglobulin deposits in tissues may be derived at least in part from antinuclear factors. Neither bound immunoglobulins nor complement was observed in liver parenchyma of the two patients with chronic liver disease or in two patients with systemic lupus and liver pathology. It thus seems doubtful that serum antibodies play a primary role in the pathogenesis of forms of chronic liver disease associated with positive LE cell tests. Images PMID:4164259

Svec, Kathryn H.; Blair, John D.; Kaplan, Melvin H.

1967-01-01

36

VGCC antibody-positive paraneoplastic cerebellar degeneration presenting with positioning vertigo.  

PubMed

A 70-year-old woman developed paraneoplastic cerebellar degeneration (PCD) due to P/Q-type and N-type voltage-gated calcium channel antibodies and small cell lung cancer, the main clinical manifestations of which were severe positioning vertigo and vomiting. Loss of the visual suppression of caloric nystagmus, spontaneous downbeat nystagmus, periodic alternating nystagmus, and positioning vertigo in our patient most probably corresponds to the cerebellar flocculus/paraflocculus lesion caused by PCD. PMID:21678073

Ogawa, Emina; Sakakibara, Ryuji; Kawashima, Kengo; Yoshida, Tomoe; Kishi, Masahiko; Tateno, Fuyuki; Kataoka, Manabu; Kawashima, Tatsuo; Yamamoto, Masahiko

2011-12-01

37

The sera from adult patients with suggestive signs of autoimmune diseases present antinuclear autoantibodies that cross-react with Leishmania infantum conserved proteins: Crude Leishmania histone and Soluble Leishmnia antigens.  

PubMed

Visceral leishmaniasis has been associated with hyper-gammaglobulinemia and antinuclear antibodies and may simulate systemic lupus erythematosus. Sera from patients with visceral leishmaniasis have been shown to strongly react against conserved proteins from the parasite, such as ribosomal and histones. Some of these proteins have also been described as immunogenic in several auto-immune syndromes, and the detection of antibodies against them is considered to be indicative of disorder in the immune system. This study aimed to assess by enzyme-linked immunosorbent assay, test routinely employed in visceral leishmaniasis diagnosis, the recognition of Crude Leishmania histone and Soluble Leishmania antigens proteins from Leishmania infantum by adult patients with suggestive signs of autoimmune diseases. Our results show that the humoral response generated during autoimmune diseases cross-reacts with the parasitic Crude Leishmania histone and Soluble Leishmania antigens. In these cases, higher precautions must be taken to confirm the presence of visceral leishmaniasis in front of positive serology in antinuclear antibodies positive sera, in order to avoid wrong diagnosis. PMID:25395341

Lakhal, Sami; Benabid, Meriem; Sghaier, Ines Ben; Bouratbine, Aïda; Galai, Yousr

2015-02-01

38

Heterophilic antibodies interfering with radioimmunoassay. A false-positive pregnancy test  

SciTech Connect

A young woman with amenorrhea had a consistently positive pregnancy test result (serum radioimmunoassay measurement of ..beta..-human chorionic gonadotropin hormone). No fetal or placental tissue was found after uterine curettage and exploratory laparotomy. The false-positive pregnancy test result was due to heterophilic antibovine and antigoat antibodies in the patient's serum. These antibodies interfered with radioimmunoassays using goat antibodies. This case shows that serum heterophilic antibodies can interfere with immunoassays and result in unnecessary diagnostic procedures and/or unnecessary treatment.

Vladutiu, A.O.; Sulewski, J.M.; Pudlak, K.A.; Stull, C.G.

1982-11-19

39

Influenza-associated MOG antibody-positive longitudinally extensive transverse myelitis: a case report.  

PubMed

BackgroundMyelin-oligodendrocyte glycoprotein antibody (MOG antibodies) was found in various demyelinated diseases. This is the first report of a patient with longitudinally extensive transverse myelitis with an extremely high titer of MOG antibodies after an influenza infection. This case supports the view that MOG antibodies are linked to longitudinally extensive transverse myelitis and that influenza infection might trigger the MOG antibodies.Case presentationA 32-year-old healthy male developed high fever, dysesthesia and paraesthesia below the C2 area, muscle weakness of the bilateral lower extremities, and urinary retention ten days after an influenza type A infection. Magnetic resonance imaging revealed a longitudinal lesion in the spinal cord extending from C2 to the spinal conus. There were no lesions in the brain or optic nerves. Established cell-based immunoassays revealed that he was positive for MOG antibodies (titer =65,536) and negative for anti-aquaporin 4 antibodies (AQP4 antibodies). He fully recovered after steroid pulse therapy followed by 60 mg prednisolone.ConclusionThis is the first report of influenza A-associated longitudinally extensive transverse myelitis with a high titer anti-MOG antibodies. Our case report supports a relationship between anti-MOG antibodies and longitudinally extensive transverse myelitis, which was triggered by influenza infection. Further studies are needed to establish the clinical significance of anti-MOG antibodies for diagnosis, treatment, and prognosis. PMID:25434485

Amano, Haruka; Miyamoto, Nobukazu; Shimura, Hideki; Sato, Douglas; Fujihara, Kazuo; Ueno, Shinichi; Nakamura, Ryota; Ueno, Yuji; Watanabe, Masao; Hattori, Nobutaka; Urabe, Takao

2014-11-30

40

Scleroderma, D-penicillamine treatment, and progressive renal failure associated with positive antimyeloperoxidase antineutrophil cytoplasmic antibodies  

Microsoft Academic Search

Progressive renal failure in patients with scleroderma is a sinister development that is usually attributed to impaired renal blood flow. In some exceptional cases, the underlying pathology is a crescentic glomerulonephritis, which has been associated with positive antineutrophil cytoplasmic antibodies, and in particular antimyeloperoxidase antibodies. The prognosis in such cases has been very poor. We report such a patient whose

Graham S. Hillis; Izhar H. Khan; John G. Simpson; Andrew J. Rees

1997-01-01

41

Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma  

PubMed Central

Introduction. Paraneoplastic encephalomyelitis (PEM) and subacute sensory neuronopathy (SSN) are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC) with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1). The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association. PMID:23320243

Lukacs, S.; Szabo, N.; Woodhams, S.

2012-01-01

42

False positive Legionella pneumophila direct immunofluorescent monoclonal antibody test caused by Bacillus cereus spores.  

PubMed

Direct immunofluorescent monoclonal antibody stain testing for Legionella pneumophila in Oklahoma lake water yielded an unknown bacillus with fluorescence intensity equal to that of L. pneumophila stock strains. The organism in question was identified as Bacillus cereus, a ubiquitous bacterium. When B. cereus cultures were studied, fluorescence was seen in spores but not in vegetative cells. Since a positive immunofluorescent monoclonal antibody test (alone) might be considered by some individuals as unequivocal to very good evidence for the presence of L. pneumophila, this finding emphasizes the importance of confirming positive stain results with cultures whenever possible. PMID:3133155

Flournoy, D J; Belobraydic, K A; Silberg, S L; Lawrence, C H; Guthrie, P J

1988-02-01

43

Vancomycin-induced neutropenia in a patient positive for an antineutrophil antibody.  

PubMed

A 48-year-old man, hospitalized after experiencing subarachnoid hemorrhage secondary to a basilar aneurysm, received vancomycin for methicillin-resistant Staphylococcus aureus sepsis. He developed neutropenia 16 days after the start of vancomycin therapy, and his white blood cell count decreased to a nadir of 1200 cells/mm3. Vancomycin was discontinued, and granulocyte-colony stimulating factor (G-CSF) therapy was begun. The patient was rechallenged with a single dose of vancomycin 1 g in preparation for intraarterial aneurysm coiling. His white blood cell count dropped to 600 cells/mm3 but returned to normal with continued G-CSF therapy. A diagnosis of vancomycin-induced neutropenia was considered. Subsequent testing by granulocyte agglutination and granulocyte immunofluorescence assays revealed that his serum was positive for an antigranulocyte antibody. A test for HLA antibody reactivity was negative. Monoclonal antibody immobilization of granulocyte antigens assay failed to determine the antigen specificity of his granulocyte antibody. PMID:12066971

Schwartz, Michael D

2002-06-01

44

Anti-N-methyl-D-aspartate receptor encephalitis with positive serum antithyroid antibodies, IgM antibodies against mycoplasma pneumoniae and human herpesvirus 7 PCR in the CSF.  

PubMed

We report the case of a boy with an encephalopathy associated with extrapyramidal and psychiatric symptoms and anti-N-methyl-D-aspartate receptor antibodies. He had positive serum antithyroid antibodies, IgM antibodies against Mycoplasma pneumoniae and human herpesvirus 7 polymerase chain reaction in the cerebrospinal fluid. He was successfully treated with rituximab, after steroids, intravenous immunoglobulin and plasma exchange. The pathophysiology of this disorder may be post-infectious and autoimmune. PMID:25222311

Venâncio, Paulo; Brito, Maria João; Pereira, Gabriela; Vieira, José Pedro

2014-08-01

45

Social-movement analysis of the American antinuclear movement  

SciTech Connect

Utilizing data from a survey of participants at the May 6, 1979 antinuclear rally in Washington, DC (N = 420), this dissertation explored some of the major structural and ideological characteristics of the American Antinuclear Movement. By organizing the data around three of the key analytical concepts in the study of social movements - mobilization, recruitment, and ideology - the author was able to derive from the demonstration sample a descriptive and illustrative analysis of those individuals, organizations, and processes involved in the national antinuclear crusade. Given that few researchers have actively studied the antinuclear movement beyond the scope of local or regional protests, this work constitutes the only empirical study to date examining a cross section of the movement's participants from a sociological perspective. It is also one of the few attempts to use a national demonstration as a social laboratory for the study of a social movement in general. In terms of the mobilization variables examined in the study, it was found that organizational networks, past movement activism, and individual resources were important factors in the May 6 mobilization effort. While less than one-half of the demonstrators were part of the antinuclear organizational network per se, most of them had been active in the major protest movements of the 1960's and 1970's. The demonstrators were relatively high in socio-economic resources and had occupational or educational schedules conducive to creating the necessary discretionary time for movement participation.

Ladd, A.E.

1981-01-01

46

Antibody  

NSDL National Science Digital Library

Antibody: A blood protein that is produced in response to and counteracts an antigen. Antibodies are produced in response to disease and help the body fight against the particular disease. In this way, antibodies help the body develop an immunity to disease.

Darryl Leja (National Human Genome Research Institute REV)

2005-04-04

47

Studies on production of anticollagen antibodies in silicosis  

SciTech Connect

Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of antihuman type I collagen (HI) and anti-human type Ill collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis. 49 refs. 6 figs., 6 tabs.

Nagaoka, Tadasu; Tabata, Masaji; Kobayashi, Kenichi; Okada, Akira (Kanazawa Univ. (Japan))

1993-01-01

48

Positive hepatitis B virus core antibody in HIV infection-false positive or evidence of previous infection?  

PubMed

Isolated HBV core antibody (anti-HBc) is defined as the presence of anti-HBc with a negative HBV surface antigen (HBsAg) and HBV surface antibody (anti-HBs <10?IU/l). In patients infected with HIV with isolated anti-HBc, the aim was to determine: The prevalence of isolated positive anti-HBc; The most effective method of identifying which patients have had previous Hepatitis B Virus (HBV) infection; The prevalence of false positive anti-HBc. HBV serology results were identified from 539 patients infected with HIV sampled between January 2010 and December 2012. In those with an isolated anti-HBc and negative anti-HBe, a second anti-HBc test was carried out using a different assay. Samples were also screened for HBV DNA. The anti-retroviral regimens at time of screening were documented. 101/539 had an isolated anti-HBc. Of these, 32 (32%) had a positive anti-HBe (including 1 equivocal) and 69(68%) were anti-HBe negative. Of those negative for anti-HBe, 32 were tested for both DNA and a second anti-HBc. Of these 26 (81%) were on cART at time of HBV testing, with 25 (78%) on ART with anti-HBV activity. The prevalence of isolated anti-HBc was 19%. Only 32% were also anti-HBe positive, whereas 97% of those anti-HBe negative were positive on a second anti-HBc assay suggesting lack of utility of anti-HBe in resolving serological quandaries. One subject (3%) had a false positive anti-HBc. There was no evidence of chronic HBV but 78% patients were on HBV-suppressive combination anti-retroviral therapy. J. Med. Virol. 87:208-212, 2015. © 2014 Wiley Periodicals, Inc. PMID:25174739

Pallawela, S N S; Sonnex, C; Mabayoje, D; Bloch, E; Chaytor, S; Johnson, M A; Carne, C; Webster, D P

2015-02-01

49

Screening test for rheumatic diseases: a combined enzyme immunoassay of rheumatoid factors and antibodies to DNA and extractable nuclear antigens.  

PubMed Central

Three hundred and one sera from patients with rheumatic and other diseases were investigated using a simple enzyme immunoassay for screening of rheumatoid factors and antinuclear antibodies. The assay had a sensitivity of 77% for systemic lupus erythematosus, 90% for the primary sicca syndrome, and 89% for rheumatoid arthritis. Only 13% of sera from patients with chronic non-rheumatic diseases were positive. The test was further evaluated in a group of patients with suspected rheumatic disease who were followed up for six to 12 months. The test was positive in 16 of 17 sera from patients with connective tissue diseases but in only seven of 36 sera (19%) from patients with non-inflammatory joint diseases. None of the four patients with reactive arthritis was positive by this test. The sensitivity of the assay was comparable with that of the agglutination and immunofluorescence tests for rheumatoid factors and antinuclear factors. For the screening of rheumatoid factor and antinuclear antibodies this kind of test panel offers a simple alternative to the conventional tests for small clinical laboratories and for those in which the autoantibody tests could be automated, as the assay can be performed in one working day and only one dilution of serum is needed to obtain a quantitative result. Images Figure PMID:3323254

Kurki, P; Gripenberg, M; Partanen, P; Helve, T

1987-01-01

50

Anti-Glutamate ?2 Receptor Antibody-Positive and Anti-N-Methyl-D-Aspartate Receptor Antibody-Negative Lobar Encephalitis Presenting as Global Aphasia and Swallowing Apraxia  

PubMed Central

Background Little is known about the difference between anti-N-methyl-D-aspartate receptor (NMDAR) antibody-positive encephalitis and anti-glutamate receptor (GluR) antibody-positive encephalitis. Objectives To characterize anti-GluR antibody-positive encephalitis. Methods We report a 33-year-old man with nonparaneoplastic anti-GluR ?2, ?1 and ?2 antibody-positive and anti-NMDAR antibody-negative encephalitis, using neuropsychological tests and imaging studies including magnetic resonance imaging and single photon emission computed tomography (SPECT) with a 99mTc-ethylcysteinate dimer. Results The patient exhibited global aphasia and swallowing apraxia (inability to transfer food to the pharyngeal cavity without sialorrhea). He was treated with 3 courses of corticosteroid pulse therapy and had recovered markedly 3 weeks after onset. Magnetic resonance diffusion-weighted images revealed hyperintensity in the bilateral frontal and left parietal cortices. Seven months later, a small area of hyperintensity in the left supramarginal gyrus remained. SPECT revealed hypoperfusion in extensive regions of the bilateral frontal lobes and left supramarginal gyrus. Thirteen months later, blood flow reduction was restricted to diffuse areas in the frontal lobes. Conclusions Frontal lobar encephalitis without medial temporal involvement, marked cognitive impairment with a relatively preserved level of consciousness, and a favorable response to corticosteroid therapy, with nearly reversible cortical damage, may characterize anti-GluR antibody-positive encephalitis.

Hayata, Yuki; Hamada, Kensuke; Sakurai, Yasuhisa; Sugimoto, Izumi; Mannen, Toru; Takahashi, Yukitoshi

2014-01-01

51

Mesothelial Cell and Anti-Nuclear Autoantibodies Associated with Pleural Abnormalities in an Asbestos Exposed Population of Libby MT  

PubMed Central

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p =0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects (p=0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease. PMID:22085844

Marchand, Lucas S.; St-Hilaire, Sophie; Putnam, Elizabeth A.; Serve, Kinta M.; Pfau, Jean C.

2011-01-01

52

Segmental testicular infarction due to minocycline-induced antineutrophil cytoplasmic antibody--positive vasculitis.  

PubMed

Segmental testicular infarction is an uncommon clinical entity marked by acute scrotal pain and swelling. Classically, these appear as wedge-shaped, avascular, hypoechoic lesions on a testicular ultrasound. We present a unique case of testicular infarct caused by an antineutrophil cytoplasmic antibody-positive vasculitis secondary to the use of the antibiotic minocycline. The patient's symptoms resolved with cessation of minocycline. We suggest that patients who present with otherwise unexplained testicular infarction undergo a careful review of medications to uncover a potential cause. PMID:24793001

Lyon, Timothy D; Ferroni, Matthew C; Casella, Daniel P; D'Agostino, Louis A; Jackman, Stephen V

2014-07-01

53

Antineutrophil cytoplasmic antibody-positive conversion and microscopic polyangiitis development in patients with idiopathic pulmonary fibrosis  

PubMed Central

Background Increasing evidence indicates that antineutrophil cytoplasmic antibody (ANCA)-positive conversion occurs in patients initially diagnosed with idiopathic pulmonary fibrosis (IPF) and as a result, some of these patients develop microscopic polyangiitis (MPA). However, the incidence density of these patients is not well known. Objectives To explore the incidence of ANCA-positive conversion and development of MPA during the disease course in patients with IPF and to evaluate whether corticosteroid therapy reduces MPA development in patients with IPF with myeloperoxidase (MPO)-ANCA positivity at diagnosis or who later acquire MPO-ANCA positivity. Methods We retrospectively analysed the medical records of 504 Asian patients with IPF treated at our institution in Saitama, Japan. Results Of the 504 patients with IPF, 20 (4.0%) had MPO-ANCA and 16 (3.2%) had PR-3-ANCA when first evaluated. In 264 of 504 patients with IPF, ANCA was measured repeatedly and seroconversion to MPO-ANCA and PR3-ANCA occurred in 15 (5.7%) and 14 (5.3%) patients, respectively, and 9 of 35 patients who were either MPO-ANCA positive at IPF diagnosis or who subsequently seroconverted developed MPA. None of the nine patients who developed MPA had been previously treated with steroids. The incidence of MPA tended to be lower in patients treated than not treated with corticosteroids although this was not statistically significant. Conclusions Some patients with IPF with MPO-ANCA positivity at IPF diagnosis or with MPO-ANCA-positive conversion during follow-up developed MPA. Clinical trials to determine whether corticosteroid therapy can reduce MPA development and prolong survival in MPO-ANCA-positive patients with IPF should be considered.

Kagiyama, Naho; Takayanagi, Noboru; Kanauchi, Tetsu; Ishiguro, Takashi; Yanagisawa, Tsutomu; Sugita, Yutaka

2015-01-01

54

A subset of ulcerative colitis with positive proteinase-3 antineutrophil cytoplasmic antibody  

PubMed Central

A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were ineffective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates that ulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden. PMID:19058341

Xu, Jin; Yang, Chuan-Hua; Chen, Xiao-Yu; Li, Xu-Hang; Dai, Min; Xiao, Shu-Dong

2008-01-01

55

The Prevalence of Positive Serum Anticardiolipin Antibodies and Asymptomatic Bacteriuria in Women with Recurrent Abortions  

PubMed Central

Objective The asymptomatic colonization of the urinary tract in pregnant women may result in severe medical and obstetric complications. The aim of this study was to study the prevalence of asymptomatic bacteriuria in cases of elevated levels of the anticardiolipin antibody in women who experience spontaneous abortions. Materials and Methods: A total of 12 women were enrolled in this case control study, including 60 patients with a history of three or more abortions and 60 healthy pregnant women. All participants were screened for ACL (IgG) and with a urine culture. Results: Overall, 19 (31.7%) patients and seven (11.7%) healthy pregnant women were positive for ACL. The mean concentrations were 67.1±27.2 IU/mL in the patients and 17.41±6.12 IU/mL in the healthy controls (p?0.05). In the 60 patients, only 17 (28.3%) had significant bacteriuria, whereas 5 (8.3%) women in the control group had significant bacteriuria. The statistical analysis revealed a highly significant difference. Of the 19 patients with a positive elevation of ACL, 11 (57.9%) had significant bacteriuria, and eight (42.1%) had non-significant bacteriuria. Six patients had ACL-negative results associated with significant bacteriuria. The statistical analysis revealed a highly significant difference. Conclusion: A high serum anticardiolipin level was prevalent in women who experienced recurrent abortions associated with asymptomatic bacteriuria.

Yaseen Al-khayat, Zakarea Abdullah; Waheda, Nabeel Elia; Shaker, Nabaz Faisal

2013-01-01

56

Central retinal vein occlusion in a pediatric patient with SLE and antiphospholipid antibodies without anti-cardiolipin or anti-?2 glycoprotein I antibodies  

PubMed Central

Background Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis, and is found in patients with systemic lupus erythematosus. Its diagnosis requires the presence of both clinical and laboratory findings, such as positive anti-cardiolipin and anti-?2 glycoprotein I antibodies and lupus anticoagulant. However, cardiolipin is a minor component of the vascular endothelial cells in human, and phosphatidylcholine and phosphatidylethanolamine are major components. Case presentation A 15-year-old female suddenly developed massive left intraretinal hemorrhaging due to central retinal vein occlusion. She also had a butterfly rash, and her laboratory findings revealed positive serum anti-nuclear antibodies and decreased serum complement. During this episode, she was diagnosed with systemic lupus erythematosus. Although she was negative for serum anti-cardiolipin IgG and anti-?2 glycoprotein I antibodies as well as lupus anticoagulant, her serum anti-phosphatidylcholine, anti-phosphatidylethanolamine, anti-phosphatidylinositol and phosphatidylserine IgG antibodies levels were increased. Conclusion Pediatric cases of central retinal vein occlusion are rare. Even in patients without anti-cardiolipin or anti-?2 glycoprotein I antibodies and lupus anticoagulant, there is the potential for the development of antiphospholipid antibody-related thrombosis. PMID:24885875

2014-01-01

57

The Drug User's Identity and How It Relates to Being Hepatitis C Antibody Positive: A Qualitative Study  

ERIC Educational Resources Information Center

The increasing health problem of hepatitis C virus infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. injecting drug users). There is a lack of information about the knowledge, perceptions and feelings that injecting drug users hold about their hepatitis C antibody positive

Copeland, Lorraine

2004-01-01

58

Evaluation of disulfide bond position to enhance the thermal stability of a highly stable single domain antibody.  

PubMed

Single domain antibodies are the small recombinant variable domains derived from camelid heavy-chain-only antibodies. They are renowned for their stability, in large part due to their ability to refold following thermal or chemical denaturation. In addition to refolding after heat denaturation, A3, a high affinity anti-Staphylococcal Enterotoxin B single domain antibody, possesses a melting temperature of ?84°C, among the highest reported for a single domain antibody. In this work we utilized the recently described crystal structure of A3 to select locations for the insertion of a second disulfide bond and evaluated the impact that the addition of this second bond had on the melting temperature. Four double-disulfide versions of A3 were constructed and each was found to improve the melting temperature relative to the native structure without reducing affinity. Placement of the disulfide bond at a previously published position between framework regions 2 and 3 yielded the largest improvement (>6°C), suggesting this location is optimal, and seemingly provides a universal route to raise the melting temperature of single domain antibodies. This study further demonstrates that even single domain antibodies with extremely high melting points can be further stabilized by addition of disulfide bonds. PMID:25526640

Zabetakis, Dan; Olson, Mark A; Anderson, George P; Legler, Patricia M; Goldman, Ellen R

2014-01-01

59

Evaluation of Disulfide Bond Position to Enhance the Thermal Stability of a Highly Stable Single Domain Antibody  

PubMed Central

Single domain antibodies are the small recombinant variable domains derived from camelid heavy-chain-only antibodies. They are renowned for their stability, in large part due to their ability to refold following thermal or chemical denaturation. In addition to refolding after heat denaturation, A3, a high affinity anti-Staphylococcal Enterotoxin B single domain antibody, possesses a melting temperature of ?84°C, among the highest reported for a single domain antibody. In this work we utilized the recently described crystal structure of A3 to select locations for the insertion of a second disulfide bond and evaluated the impact that the addition of this second bond had on the melting temperature. Four double-disulfide versions of A3 were constructed and each was found to improve the melting temperature relative to the native structure without reducing affinity. Placement of the disulfide bond at a previously published position between framework regions 2 and 3 yielded the largest improvement (>6°C), suggesting this location is optimal, and seemingly provides a universal route to raise the melting temperature of single domain antibodies. This study further demonstrates that even single domain antibodies with extremely high melting points can be further stabilized by addition of disulfide bonds. PMID:25526640

Zabetakis, Dan; Olson, Mark A.; Anderson, George P.; Legler, Patricia M.; Goldman, Ellen R.

2014-01-01

60

Guillain-Barré syndrome-like-onset neurosarcoidosis positive for immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody.  

PubMed

Anti-ganglioside antibodies have been reported in various peripheral neuropathies, including Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, Fisher syndrome, monoclonal gammopathy-associated neuropathy, and other idiopathic neuropathies. To our knowledge, there has been no report of anti-ganglioside-positive sarcoidosis. We report a 62-year-old man with acute weakness of the limbs and sensory disturbance of the right arm and trunk resembling GBS. Soluble interleukin-2 receptor and angiotensin-converting enzyme levels were elevated. Anti-ganglioside antibodies (immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody [IgG anti-GalNAc-GD1a antibody]) were detected. Neurophysiological examination demonstrated axonal neuropathy. Bilateral hilar lymphadenopathy was demonstrated on a chest CT scan, and abnormal uptake of 67 Gallium was detected by scintigraphy. The ratio of CD4 to CD8 was elevated in bronchoalveolar lavage fluid. Noncaseating epithelioid cell granulomas were detected in a specimen obtained via transbronchial lung biopsy. Because intravenous immunoglobulin did not improve the symptoms, we commenced steroid pulse therapy followed by oral prednisolone therapy. After steroid therapy, he recovered fully. Because the findings in our patient fulfilled the criteria for neurosarcoidosis, we diagnosed his illness as probable neurosarcoidosis. To the best of our knowledge, this is the first patient with GBS-like-onset neurosarcoidosis positive for anti-IgG anti-GalNAc-GD1a antibody. PMID:23916762

Chatani, H; Tanaka, M; Nagata, T; Araki, T; Kusunoki, S

2014-01-01

61

Importance of checking anti-glomerular basement membrane antibody status in patients with anti-neutrophil cytoplasmic antibody-positive vasculitis.  

PubMed

The case is reported of a 68-year-old man with perinuclear anti-neutrophil cytoplasmic antibody (pANCA)-associated glomerulonephritis who developed antibodies to glomerular basement membrane (anti-GBM) resulting in end stage renal failure. His pANCA titre on admission was 1:1024 IgG and he was anti-myeloperoxidase positive. A renal biopsy showed advanced sclerosing necrotising glomerulonephritis consistent with a pauci-immune ANCA-positive glomerulonephritis. He was treated with steroids and cyclophosphamide. His serum creatinine profile improved. He had a relapse of disease 16 months later, which was successfully treated. After a further 16 months, he presented with acute renal failure (creatinine 1060 micromol/l). His pANCA titre on admission was 1:64 IgG. This was treated as a further relapse of ANCA-positive vasculitis. He became oliguric and his haemoglobin concentration fell. Eight days after admission, he was found to be strongly positive for anti-GBM (138 U/ml). Despite receiving cyclophosphamide, steroids and plasma exchange, he remained dialysis-dependent. PMID:18424581

Gallagher, J L; Sinha, S; Reeve, R; Kalra, P A

2008-04-01

62

Heterophile antibody positive, acute cytomegaloviral infection in an immunocompetent pre-teen: An atypical presentation of an atypical infection.  

PubMed

Mononucleosis and mononucleosis-like illnesses comprise a significant proportion of pediatric and adolescent infectious illnesses. By far, the most common cause of these illnesses is Epstein-Barr virus, which causes mononucleosis, and a distant second is cytomegalovirus, which is the most common cause of mononucleosis-like illnesses. This case provides an interesting juxtaposition of laboratory findings of an adolescent who was heterophile antibody positive but acute Epstein-Barr virus antigen-antibody negative. A subsequent immunologic assay resulted in a final diagnosis of an acute cytomegaloviral infection. This is, to our knowledge, the first such report in the literature. PMID:25270386

Raja, Junaid; de Quesada, Gonzalo

2014-09-27

63

Trends in anti-nuclear protests in the United States, 1984-1987  

SciTech Connect

This report updates previous RAND research on U.S. anti-nuclear protest groups, examines trends in anti-nuclear and related protests, and assess what these trends may imply for possible terrorist violence, either by terrorists infiltrating the anti-nuclear movement or violent elements arising within the movement. Two recent trends in protest activity may signal greater militancy in the movement. First, the number of protesters who are willing to face arrest, fines, and imprisonment has steadily increased over the past four years. In the first eleven months of 1987, nearly 3,000 protesters were arrested for anti-nuclear civil disobedience, compared with 1,056 in 1984. Second, some large, diverse groups of protesters have stretched the ability of their own organizers to control events involving civil disobedience. Consequently, the number of skirmishes between protesters and security personnel has increased. Third, radical environmentalist groups previously uninvolved in anti-nuclear activities have recently organized protests at uranium mines. Regular involvement by such groups in anti-nuclear protests, coupled with the trend toward greater cooperation between peace activists and environmentalists over such issues as uranium mining, nuclear testing, land and sea use, and transport and storage of toxic waste, could signal a more volatile, though not necessarily more violent, future for the anti-nuclear movement.

Ondaatje, E.H.

1989-01-01

64

False positive legionella serology in campylobacter infection: campylobacter serotypes, duration of antibody response and elimination of cross-reactions in the indirect fluorescent antibody test.  

PubMed

Sera from 83 patients with campylobacter gastroenteritis were examined for the presence of legionella antibodies by indirect immunofluorescence. Twenty-one patients (25%) had positive titres (> or = 16) including 11 patients with titres of > or = 128. Legionella seropositivity persisted in 5 of 9 patients (55%) studied for 6-9 months. Campylobacter isolates were serotyped by the Penner scheme. Isolates associated with legionella seropositivity included Penner types 1, 2 and 4, the common endemic serotypes in England. Campylobacter blocking fluids were prepared from a range of Penner reference strains. The blocking fluid prepared from Penner type 11 was the most efficient at inhibiting the false-positive legionella titres. Using this absorption step legionella titres were inhibited from 24 of 26 patients (92%) with campylobacter but not from 8 patients with culture-proven legionnaires' disease. We recommend that this method is incorporated into routine diagnostic legionella serology in order to eliminate false-positive reactions due to campylobacter. PMID:8150008

Marshall, L E; Boswell, T C; Kudesia, G

1994-04-01

65

Positive dermal hypersensitivity and specific antibodies in workers exposed to bio-engineered enzymes  

SciTech Connect

Thirty-six employees who produced industrial enzymes from bio-engineered strains of bacteria and fungi were evaluated by skin prick testing and enzyme linked immunosorbent assays for specific IgE and IgG antibodies. The workers complained of asthma- and flu-like' symptoms which generally lessened away from work. The enzymes evaluated were {alpha}-amylase from A. niger (ind-AAN), B. licheniformis (ind-AAL) and B. subtilis (ind-AAS); purified {alpha}-amylase from B. subtilis (AAS) and A. niger (AAN); alkaline protease from B. licheniformis (ind-APL) and purified alkaline protease (APL); amylase glucosidase from A. niger (ind-AGN) and purified amylase glucosidase (AGN). Significantly positive skin tests were found for APL, AGN and ind-AAN. Significantly elevated specific IgE results were observed for AAN, AGN, and ind-AAN; elevated specific IgGs were observed for AAN, ind-AAN, ind-AAS, ind-AAL and ind-AGN. Radioimmunoassays of air filter samples (using sera with high Ab titers) for 4 of the ind-enzymes showed only ind-AAN at extremely high environmental levels. These results indicate that occupational exposure to some ind-enzymes causes immediate onset dermal hypersensitivity reactions. The results are equivocal as to whether these reactions are IgE mediated, as IgE titers were low. Contrary to this, IgG titers were extremely high and suggest that these biomarkers can be used as indicators of both individual exposure and environmental analyses.

Biagini, R.E.; Henningsen, G.M.; Driscoll, R.; MacKenzie, B.A.; Wilcox, T.; Scinto, J.D.; Bernstein, D.M.; Swanson, M. (Univ. of Cincinnati, OH (United States) Mayo Clinic, Rochester, MN (United States))

1991-03-15

66

PET-positive extralimbic presentation of anti-glutamic acid decarboxylase antibody-associated encephalitis.  

PubMed

Anti-glutamic acid decarboxylase (GAD) antibody-associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66-year-old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma-associated myasthenia gravis presented with generalised tonic-clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non-specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti-GAD antibody. Anti-GAD antibody-associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non-specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences] . PMID:25042574

Kojima, Gotaro; Inaba, Michiko; Bruno, Michiko K

2014-09-01

67

Monoclonal antibody against bacterial lipopolysaccharide cross-reacts with DNA-histone.  

PubMed Central

Monoclonal antibodies to bacterial lipopolysaccharide (LPS) were prepared by fusing spleen cells from BALB/c mice immunized with Salmonella Minnesota Re 595 LPS to the mouse myeloma cell line P3U1. One of them, designated RS01, revealed a strong positive antinuclear activity and reacted with DNA-histone. RS01 also bound specifically to Salmonella Minnesota Re 595 LPS and eliminated the biological activity of LPS. The Salmonella completely inhibited the ANA activity of RS01 and DNA-histone blocked the reactivity of RS01 with LPS. Thus, it is clear that an anti-LPS monoclonal antibody, RS01 cross-reacts with DNA-histone. PMID:3542315

Sumazaki, R; Fujita, T; Kabashima, T; Nishikaku, F; Koyama, A; Shibasaki, M; Takita, H

1986-01-01

68

West Greenland harbour porpoises assayed for antibodies against Toxoplasma gondii: false positives with the direct agglutination method.  

PubMed

We assayed blood/tissue fluid samples from 20 harbour porpoises Phocoena phocoena from western Greenland coastal waters for antibodies against the protozoan parasite Toxoplasma gondii by the direct agglutination test (DAT). Nine individuals (45%) were interpreted to be seropositive at 1:40 dilution and 4 (20%) were seropositive up to 1:160. Samples from these individuals were assayed by an enzyme-linked immunosorbent assay (ELISA), and tissue samples of the DAT-positive animals were tested by a nested polymerase chain reaction (nPCR). Results from both methods were negative, suggesting the absence of infection in the tested animals. After chloroform clean-up, all were negative when re-assayed by DAT. We concluded that infection with T. gondii was absent in all 20 animals, despite the initially positive DAT results, and that the false positives resulted from non-specific adherence to tachyzoites in the DAT assay which could be removed by the chloroform clean-up method. Our results suggest that detecting antibodies against T. gondii using the DAT or the modified agglutination technique, particularly on samples from Arctic marine animals which often are rich in lipids, may lead to false positive results. For such samples, the use of ELISA or PCR on available tissue samples may be advocated as confirmatory tests in order to avoid false positives and overestimating seroprevalence. PMID:24695231

Blanchet, Marie-Anne; Godfroid, Jacques; Breines, Eva Marie; Heide-Jørgensen, Mads-Peter; Nielsen, Nynne Hjort; Hasselmeier, Ilka; Iversen, Maria; Jensen, Silje-Kristin; Åsbakk, Kjetil

2014-04-01

69

Biological Evaluation of 131I- and CF750-Labeled Dmab(scFv)-Fc Antibodies for Xenograft Imaging of CD25-Positive Tumors  

PubMed Central

A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was produced via recombinant expression in Pichia pastoris. The Dmab(scFv)-Fc antibody forms a dimer in solution, and it specifically binds CD25-positive tumor cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was labeled with the 131I isotope and CF750 fluorescent dye, respectively. After intravenous injection of mice bearing CD25-positive tumor xenografts, tumor uptake of the 131I-Dmab(scFv)-Fc antibody was visible at 1?h, and clear images were obtained at 5?h using SPECT/CT. After systemic administration of the CF750-Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1?h, and tumor xenografts could be kinetically imaged within 9?h after injection. These results indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25-positive tumor cells, suggesting the potential of this antibody as an imaging agent for the diagnosis of lymphomatous-type ATLL. PMID:24864244

Fan, Qing; Cai, Huawei; Yang, Hao; Li, Lin; Yuan, Cen; Lu, Xiaofeng; Wan, Lin

2014-01-01

70

Upper gastrointestinal Kaposi's sarcoma in patients positive for HIV antibody without cutaneous disease  

Microsoft Academic Search

Six patients with antibodies to the human immunodeficiency virus (HIV) and with persistent gastrointestinal symptoms of HIV infection but without cutaneous lesions of Kaposi's sarcoma underwent endoscopy. Four also underwent barium meal examination. In all six cases small lesions were seen in the stomach at endoscopy, and histological examination of biopsy specimens taken from the lesions confirmed the diagnosis of

I G Barrison; S Foster; J W Harris; A J Pinching; J G Walker

1988-01-01

71

Ado-trastuzumab Emtansine (T-DM1): an antibody-drug conjugate (ADC) for HER2-positive breast cancer.  

PubMed

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that combines the antitumor properties of the humanized anti-human epidermal growth factor receptor 2 (HER2) antibody, trastuzumab, with the maytansinoid, DM1, a potent microtubule-disrupting agent, joined by a stable linker. Upon binding to HER2, the conjugate is internalized via receptor-mediated endocytosis, and an active derivative of DM1 is subsequently released by proteolytic degradation of the antibody moiety within the lysosome. Initial clinical evaluation led to a phase III trial in advanced HER2-positive breast cancer patients who had relapsed after prior treatment with trastuzumab and a taxane, which showed that T-DM1 significantly prolonged progression-free and overall survival with less toxicity than lapatinib plus capecitabine. In 2013, T-DM1 received FDA approval for the treatment of patients with HER2-positive metastatic breast cancer who had previously received trastuzumab and a taxane, separately or in combination, the first ADC to receive full approval based on a randomized study. PMID:24967516

Lambert, John M; Chari, Ravi V J

2014-08-28

72

Anti-Ri antibody positive opsoclonus-myoclonus in a male patient with breast carcinoma  

Microsoft Academic Search

.   A 65-year-old male patient developed truncal ataxia, opsoclonus and myoclonus. In the serum anti-Ri antibodies were found,\\u000a which led to the detection of a small adenocarcinoma of the breast. Other prominent clinical features were an excessive startle\\u000a response and behavioral disorders, such as anxiety and impatience. These features suggest an immune response against both\\u000a Nova-1 and Nova-2 antigens throughout

Paul W. Wirtz; Peter A. E. Sillevis Smitt; Jorrit I. Hoff; Bertie de Leeuw; Gert Jan Lammers; Sjoerd G. van Duinen; Jan J. Verschuuren

2002-01-01

73

Patterns of Human Papillomavirus DNA and Antibody Positivity in Young Males and Females, Suggesting a Site-Specific Natural Course of Infection  

PubMed Central

Background To monitor the impact of human papillomavirus types 16 and 18 vaccine on HPV infection dynamics in the Netherlands, we started an ongoing study in sexually transmitted infection (STI) clinics in 2009. Here, we analyze baseline type-specific HPV DNA and HPV-specific antibody positivity rates. Methods We enrolled 3569 men and women, 16–24 years of age, from 14 STI clinics, and estimated genital and anal HPV DNA and antibody positivity rates of 7 main carcinogenic HPV types. Generalized estimating equations regression analyses were applied to determine risk factors for, and associations between, type-specific HPV DNA and antibody positivity. Results Genital HPV DNA positivity rates were higher in women than in men; anal HPV DNA was especially high in men who have sex with men (MSM). HPV antibody seropositivity rates were also highest in women and MSM. High-risk sexual behavior was predictive of both HPV DNA and antibody positivity. Despite a strong correlation in serological profiles for multiple HPV types, seropositivity was independently associated with homologous HPV DNA detection. Conclusions HPV DNA and antibody positivity rates are higher in women and MSM than in heterosexual men, but their association is similar across gender. This suggests a site-specific natural course of infection. PMID:23637760

Vriend, Henrike J.; Bogaards, Johannes A.; van der Klis, Fiona R. M.; Scherpenisse, Mirte; King, Audrey J.; van der Sande, Marianne A. B.

2013-01-01

74

Characterization of antibody drug conjugate positional isomers at cysteine residues by peptide mapping LC-MS analysis.  

PubMed

Antibody-drug conjugates (ADCs) are becoming a major class of oncology therapeutics. Because ADCs combine the monoclonal antibody specificity with the high toxicity of a drug, they can selectively kill tumor cells while minimizing toxicity to normal cells. Most of the current ADCs in clinical trials are controlled, but heterogeneous mixtures of isomers and isoforms. Very few protocols on ADC characterization at the peptide level have been published to date. Here, we report on the improvement of an ADC peptide mapping protocol to characterize the drug-loaded peptides by LC-MS analysis. These methods were developed on brentuximab vedotin (Adcetris(®)), a commercial ADC with an average of four drugs linked to interchain cysteine residues of its antibody component. Because of the drug hydrophobicity, all the steps of this protocol including enzymatic digestion were improved to maintain the hydrophobic drug-loaded peptides in solution, allowing their unambiguous identification by LC-MS. For the first time, the payloads positional isomers observed by RP-HPLC after IdeS-digestion and reduction of the ADC were also characterized. PMID:25596378

Janin-Bussat, Marie-Claire; Dillenbourg, Marina; Corvaia, Nathalie; Beck, Alain; Klinguer-Hamour, Christine

2015-02-15

75

Antibodies to salivary duct cells, and other autoantibodies, in patients with Sjögren's syndrome and other idiopathic autoimmune diseases  

PubMed Central

Sera from thirty patients with Sjögren's syndrome were studied for the presence of antibodies to salivary duct cells. In sixteen cases (53%) a positive result was obtained. The antibodies were present in the IgG globulins, in the IgM globulins also in nearly 50% of the IgG-positive cases, and rarely in the IgA globulins. One-third of the antibodies proved to be complement-fixing. No antibodies were found in normal controls matched for sex and age. An antinuclear factor (ANF) was demonstrated in 77% of the sera. A rheumatoid factor was shown in 48% of the sera using a modified Waaler–Rose test and in 100% using a Latex fixation test. Antibodies to smooth muscle were present in 19%. Antibodies to skeletal muscle, gastric parietal cells, thyroid antigens, adrenocortex and mitochondria were found in frequencies which did not differ significantly from those in matched controls. No correlation was demonstrated between antibodies to salivary duct cells and any of the other antibodies mentioned. Antibodies to salivary duct cells could only be absorbed with salivary gland tissue and not with other tissues. Antibodies to salivary duct cells were also found in patients with rheumatoid arthritis (22%), systemic lupus erythematosus (SLE) (18%) and myasthenia gravis (11%). They were extremely rare in patients with pernicious anaemia, autoimmune thyroiditis and idiopathic adrenocortical insufficiency. The antibodies could not be confirmed as being directed against the patient's own parotid tissue, probably due to loss of antigenic determinants as a result of the disease process. However, other findings support the opinion that Sjögren's syndrome is an idiopathic autoimmune disease. PMID:4171044

Feltkamp, T. E. W.; van Rossum, A. L.

1968-01-01

76

Alpha-Galactosyl trisaccharide epitope: Modification of the 6-primary positions and recognition by human anti-alphaGal antibody.  

PubMed

Galactose oxidase (EC 1.1.3.9, GAO) was used to convert the C-6' OH of Galbeta(1 --> 4)Glcbeta-OBn (5) to the corresponding hydrated aldehyde (7). Chemical modification, through dehydratative coupling and reductive amination, gave rise to a small library of Galbeta(1 --> 4)Glcbeta-OBn analogues (9a-f, 10, 11). UDP-[6-(3)H]Gal studies indicated that alpha1,3-galactosyltransferase recognized the C-6' modified Galbeta(1 --> 4)Glcbeta-OBn analogues (9a-f, 10, 11). Preparative scale reactions ensued, utilizing a single enzyme UDP-Gal conversion as well as a dual enzymatic system (GalE and alpha1,3GalT), taking full advantage of the more economical UDP-Glc, giving rise to compounds 6, 15-22. Galalpha(1 --> 3)Galbeta(1 --> 4)Glcbeta-OBn trisaccharide (6) was produced on a large scale (2 g) and subjected to the same chemoenzymatic modification as stated above to produce C-6" modified derivatives (23-30). An ELISA bioassay was performed utilizing human anti-alphaGal antibodies to study the binding affinity of the derivatized epitopes (6, 15-30). Modifications made at the C-6' position did not alter the IgG antibody's ability to recognize the unnatural epitopes. Modifications made at the C-6" position resulted in significant or complete abrogation of recognition. The results indicate that the C-6' OH of the alphaGal trisaccharide epitope is not mandatory for antibody recognition. PMID:15001843

Andreana, Peter R; Kowal, Przemyslaw; Janczuk, Adam J; Wang, Peng George

2004-01-01

77

Rheumatoid factor and anti-citrullinated protein antibody positivity, but not level, are associated with increased mortality in patients with rheumatoid arthritis: results from two large independent cohorts.  

PubMed

IntroductionTo investigate rheumatoid factor (RF) and anti-citrullinated protein antibody (ACPA) status and levels as predictors of mortality in two large cohorts of patients with early inflammatory arthritis (EIA).MethodsData from the Norfolk Arthritis Register (NOAR) and Leiden Early Arthritis Clinic (EAC) cohorts were used. At baseline, patients had demographic data and smoking status recorded; RF, ACPA and inflammatory markers were measured in the local laboratories. Patients were flagged with national death registers until death or censor date. Antibody status was stratified as negative, low or high positive by RF and ACPA levels individually. In addition, patients were grouped as seronegative, RF positive, ACPA positive or double antibody (RF and ACPA) positive. Cox regression models explored associations between antibody status and mortality adjusting for age, sex, smoking status, inflammatory markers and year of enrolment.Results4962 (NOAR:3053, EAC:1909) patients were included, 64% were female. Median age at onset was 56 (NOAR) and 54 (EAC) years. 35% and 42% of patients were ACPA/RF positive in NOAR and EAC respectively. When antibody status was stratified as negative, low or high positive, there were no consistent findings between the two cohorts. Double antibody positivity was associated with excess mortality in both cohorts compared to seronegative patients: NOAR and EAC respective adjusted HR (95% CI): 1.35 (1.09-1.68) and 1.58 (1.16-2.15).ConclusionsPatients with EIA who are seropositive for both RF and ACPA have increased mortality compared to those who are single positive or seronegative. Antibody level in seropositive patients was not consistently associated with excess mortality. PMID:25471696

Humphreys, Jennifer H; van Nies, Jessica; Chipping, Jackie; Marshall, Tarnya; Mil, Annette; Symmons, Deborah; Verstappen, Suzanne

2014-12-01

78

Anti-neutrophil Cytoplasmic Antibody Positivity in Five Children with Systemic Lupus Erythematosus - What is the Importance of this Finding?  

PubMed

SUMMARY Juvenile systemic lupus erythematosus (JSLE) is a systemic autoimmune chronic disease that can affect any part of the body. It is characterized by the formation of antibodies against nuclear antigens. Vasculitis may be found in SLE, but it scarcely complies with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) criteria. We report five cases of severe JSLE associated with AAV diagnosed between 1991 and 2013 in three university-based tertiary care centers. The patients (3 girls and 2 boys, aged 12 to 17) presented with a severe clinical picture and the following features: cytopenia (n=5), autoimmune hepatitis (n=3), lupus nephritis (n=1), pancreatitis (n=1), secondary antiphospholipid syndrome (n=2), impending respiratory failure (n=2), and gastrointestinal bleeding (n=1). All patients were proteinase 3 (PR3) ANCA positive, while two of them were myeloperoxidase (MPO) and PR3 ANCAs positive at the same time. They were treated with corticosteroids and immunosuppressive drugs. Remission of the disease was achieved in three patients. The course of the disease was worsening in two patients and we included rituximab (anti-CD20) in therapy. All of our patients presented as the most severe SLE patients, who must be diagnosed as soon as possible and treated very intensively. Since the comorbidity of JSLE and AAV occurs very rarely in children, presentation of such patients, their clinical pictures, treatment, and the course of the diseases are experiences that can be of great help. PMID:25580781

Bobek, Dubravka; Vukovi?, Jurica; Malenica, Branko; Bojani?, Katarina; Rukavina, Iva; Jeluši?, Marija

2014-12-01

79

A functional variant of Fcgamma receptor IIIA is associated with rheumatoid arthritis in individuals who are positive for anti-glucose-6-phosphate isomerase antibodies.  

PubMed

Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic autoantibodies in K/BxN mice, although some groups have reported that few healthy humans retain these antibodies. The expression of Fcgamma receptors (FcgammaRs) is genetically regulated and has strong implications for the development of experimental arthritis. The interaction between immune complexes and FcgammaRs might therefore be involved in the pathogenesis of some arthritic conditions. To explore the relationship between functional polymorphisms in FcgammaRs (FCGR3A-158V/F and FCGR2A-131H/R) and arthritis in individuals positive for anti-GPI antibodies, we evaluated these individuals with respect to FCGR genotype. Genotyping for FCGR3A-158V/F and FCGR2A-131H/R was performed by PCR amplification of the polymorphic site, followed by site specific restriction digestion using the genome of 187 Japanese patients with rheumatoid arthritis (including 23 who were anti-GPI antibody positive) and 158 Japanese healthy individuals (including nine who were anti-GPI antibody positive). We report here on the association of FCGR3A-158V/F functional polymorphism with anti-GPI antibody positive status. Eight out of nine healthy individuals who were positive for anti-GPI antibodies possessed the homozygous, low affinity genotype FCGR3A-158F (odds ratio = 0.09, 95% confidence interval 0.01-0.89; P = 0.0199), and probably were 'protected' from arthritogenic antibodies. Moreover, among those who were homozygous for the high affinity genotype FCGR3A-158V/V, there were clear differences in anti-human and anti-rabbit GPI titres between patients with rheumatoid arthritis and healthy subjects (P = 0.0027 and P = 0.0015, respectively). Our findings provide a molecular model of the genetic regulation of autoantibody-induced arthritis by allele-specific affinity of the FcgammaRs. PMID:16277670

Matsumoto, Isao; Zhang, Hua; Muraki, Yoshifumi; Hayashi, Taichi; Yasukochi, Takanori; Kori, Yuko; Goto, Daisuke; Ito, Satoshi; Tsutsumi, Akito; Sumida, Takayuki

2005-01-01

80

In silico driven redesign of a clinically relevant antibody for the treatment of GD2 positive tumors.  

PubMed

Ganglioside GD2 is a cell surface glycolipid that is highly expressed on cancer cells of neuroectodermal origin, including neuroblastoma, retinoblastoma, melanoma, sarcomas, brain tumors and small cell lung cancer. Monoclonal antibodies (MoAb) that target GD2 have shown clinical efficacy in the treatment of GD2 expressing tumors, and are expected to be the new standard of care for the treatment of pediatric neuroblastoma. In this study, the crystal structure of anti-GD2 murine MoAb 3F8 was solved to 1.65 Å resolution and used as a template for molecular docking simulations of its antigen, the penta-saccharide head group of GD2. Molecular docking revealed a binding motif composed of 12 key interacting amino acid side-chains, involving an extensive network of interactions involving main-chain and side-chain hydrogen bonding, two Pi-CH interactions, and an important charged interaction between Arg95 of the H3 loop with the penultimate sialic acid residue of GD2. Based on in silico scanning mutagenesis of the 12 interacting amino acids from the docked 3F8:GD2 model, a single point mutation (Heavy Chain: Gly54Ile) was engineered into a humanized 3F8 (hu3F8) MoAb and found to have a 6-9 fold enhancement in antibody-dependent cell-mediated cytotoxicity of neuroblastoma and melanoma cell lines. With enhanced tumor-killing properties, the re-engineered hu3F8 has the potential be a more effective antibody for the treatment of GD2-positive tumors. PMID:23696816

Ahmed, Mahiuddin; Goldgur, Yehuda; Hu, Jian; Guo, Hong-Fen; Cheung, Nai-Kong V

2013-01-01

81

Monoclonal antibody conjugated magnetic nanoparticles could target MUC-1-positive cells in vitro but not in vivo.  

PubMed

MUC1 antigen is recognized as a high-molecular-weight glycoprotein that is unexpectedly over-expressed in human breast and other carcinomas. In contrast, C595 a monoclonal antibody (mAb) against the protein core of the human urinary epithelial machine, is commonly expressed in breast carcinomas. The aim of this study was to conjugate ultra-small super paramagnetic iron oxide nanoparticles (USPIO) with C595 mAb, in order to detect in vivo MUC1 expression. A dual contrast agent (the C595 antibody-conjugated USPIO labeled with 99mTc) was prepared for targeted imaging and therapy of anti-MUC1-expressing cancers. The C595 antibody-conjugated USPIO had good stability and reactivity in the presence of blood plasma at 37?°C. No significant differences were observed in immunoreactivity results between conjugated and nonconjugated nanoparticles. The T1 and T2 measurements show >79 and 29% increments (for 0.02?mg/ml iron concentrations) in T1 and T2 values for USPIO-C595 in comparison with USPIO, respectively. The nanoprobes showed the interesting targeting capability of finding the MUC1-positive cell line in vitro. However, we found disappointing in vivo results (i.e. very low accumulation of nanoprobes in the targeted site while >80% of the injected dose per gram was taken up by the liver and spleen), not only due to the coverage of targeting site by protein corona but also because of absorption of opsonin-based proteins at the surface of nanoprobes. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25327822

Shanehsazzadeh, Saeed; Gruettner, Cordula; Lahooti, Afsaneh; Mahmoudi, Morteza; Allen, Barry J; Ghavami, Mahdi; Daha, Fariba Johari; Oghabian, Mohammad Ali

2014-10-18

82

Optimal management of hypothyroidism, hypothyroxinaemia and euthyroid TPO antibody positivity preconception and in pregnancy.  

PubMed

Normal physiological changes of pregnancy warrant the need to employ gestation specific reference ranges for the interpretation of thyroid function tests. Thyroid hormones play crucial roles in foetal growth and neurodevelopment which are dependent on adequate supply of maternal thyroid hormones from early gestation onwards. The prevention of significant adverse obstetric and neurodevelopmental outcomes from hypothyroidism requires a strategy of empirical levothyroxine dose increases and predictive dose adjustments in pregnancy combined with regular thyroid function testing, starting before pregnancy and until the postpartum period. Subclinical hypothyroidism has been associated with an increased risk of pregnancy loss and neurocognitive deficits in children, especially when diagnosed before or during early pregnancy. Whilst trials of levothyroxine replacement for mild hypothyroidism in pregnancy have not indicated definite evidence of improvements in these outcomes, professional guidelines recommend treatment, especially if evidence of underlying thyroid autoimmunity is present. Studies of isolated hypothyroxinaemia in pregnancy have shown conflicting evidence with regards to adverse obstetric and neurodevelopmental outcomes and no causative relationships have been determined. Treatment of this condition in pregnancy may be considered in those with underlying thyroid autoimmunity. Whilst the evidence for a link between the presence of anti-TPO antibodies and increased risks of pregnancy loss and infertility is compelling, the results of ongoing randomized trials of levothyroxine in euthyroid women with underlying autoimmunity are currently awaited. Further studies to define the selection of women who require levothyroxine replacement and to determine the benefits of a predictive dose adjustment strategy are required. PMID:25200555

Chan, Shiao; Boelaert, Kristien

2015-03-01

83

Prevalence of antibodies against Treponema pallidum among HIV-positive patients in a tertiary care hospital in Mexico.  

PubMed

Our objective was to determine the seroprevalence of syphilis among HIV-infected patients in a tertiary care hospital in Mexico City. A cross-sectional study was developed, and 318 HIV-positive patients were evaluated from January to February 2013 at Hospital de Infectología, National Medical Center 'La Raza' (a tertiary care hospital specialising in infectious diseases in Mexico City). Laboratory data were screened for the detection of antibodies against Treponema pallidum. Patients completed a questionnaire relating to socio-demographic data and factors associated with syphilis. Of the 318 patients, 83% were men. The mean age ± SD was 36?±?11 years; 52% were men who have sex with men and 47% had undertaken higher education. The overall seroprevalence of syphilis among these patients was 25% (95% confidence interval 21%, 30%). Men who have sex with men had a significantly higher seroprevalence (30% vs. 15%, p?=?0.009). We conclude that, in Mexico, there is a high seroprevalence of syphilis antibodies in HIV-infected patients and that men who have sex with men are the group most affected. PMID:24713227

Mata-Marín, José Antonio; Sandoval-Sánchez, Juan Joel; Huerta-García, Gloria; Arroyo-Anduiza, Carla Ileana; Alcalá-Martínez, Enrique; Mata-Marín, Luis Alberto; Sandoval-Ramirez, Jorge Luis; Gaytán-Martínez, Jesús

2015-02-01

84

An ELISA for the detection of anti-neutrophil cytoplasm antibodies (ANCA).  

PubMed

An enzyme-linked immunosorbent assay (ELISA) has been developed for the detection of circulating anti-neutrophil cytoplasm antibodies (ANCA), which are defined by a diffuse, granular staining of the cytoplasm of alcohol-fixed human neutrophils by indirect immunofluorescence (IIF). Detection of antineutrophil cytoplasm antibodies has a high sensitivity and specificity for active Wegener's granulomatosis (WG) and reflects the effect of treatment. In the present enzyme-linked assay, immunoplates were coated with the cytoplasmic alpha fraction of neutrophils obtained from apparently healthy human donors by nitrogen bomb cavitation and subsequent Percoll gradient centrifugation. Alkaline phosphatase-labelled anti-human IgG was used as a secondary antibody. Diluted sera from 70 patients with WG and 16 patients with other diseases with anti-myeloperoxidase antibodies (anti-MPO) were examined. It is concluded that the ELISA accurately detects IIF ANCA positive patients with WG, is helpful in detecting WG patients in remission, is not influenced by the presence of anti-MPO and may help in detecting ANCA in cases with granulocyte-specific anti-nuclear antibodies since this IIF pattern obscures the IIF ANCA patterns. The ELISA with titration can be carried out in 3.5 h whereas a rapid test just to detect ANCA can be performed in 30 min. PMID:2156937

Rasmussen, N; Sjölin, C; Isaksson, B; Bygren, P; Wieslander, J

1990-02-20

85

Serum monoclonal antibodies derived from patients with multiple myeloma react with mycobacterial phosphoinositides and nuclear antigens.  

PubMed Central

The sera of 46 patients with multiple myeloma were examined for the presence of anti-tuberculosis (TB) glycolipids antibodies. In positive sera samples, anti-polynucleotides, anti-histones, anti-cardiolipin, anti-Sm and anti-RNP activities were sought. Antibodies against three different mycobacterial glycolipids were detected in 10 of the 46 sera. Three (P429, P557, P5) showed high titres of antibodies against all three different TB glycolipids. Of the 10 reactive samples, two antibodies were purified (P429, P557). P557 reacted with various polynucleotides and other antigens tested (Sm, RNP, cardiolipin, histones). One immunoglobulin (P207) which showed high activity against Sm and RNP had no activity against TB glycolipids and was employed as a control. The cross-reactivity between mycobacterial glycolipids and the nuclear antigens was further established by bi-directional competition assays with P429 and P557. Our study shows a high incidence (22%) of anti-TB glycolipids antibodies in sera of patients with monoclonal gammopathies, some of which show anti-DNA and other anti-nuclear antigens activities. This is additional evidence for the mycobacterial-nuclear antigen cross-reactivity which may suggest a possible role of infection (e.g., tuberculosis) in autoimmune diseases. PMID:2546701

Buskila, D; Abu-Shakra, M; Amital-Teplizki, H; Coates, A R; Krupp, M; Sukenik, S; Shoenfeld, Y

1989-01-01

86

Clinical and Electrophysiologic Responses to Acetylcholinesterase Inhibitors in MuSK-Antibody-Positive Myasthenia Gravis: Evidence for Cholinergic Neuromuscular Hyperactivity  

PubMed Central

Background and Purpose Patients with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-Ab)-positive myasthenia gravis (MG) show distinct responses to acetylcholinesterase inhibitors (AChEIs). Although clinical responses to AChEIs in MuSK-Ab MG are reasonably well known, little is known about the electrophysiologic responses to AChEIs. We therefore investigated the clinical and electrophysiologic responses to AChEIs in MuSK-Ab-positive MG patients. Methods We retrospectively reviewed the medical records and electrodiagnostic findings of 17 MG patients (10 MuSK-Ab-positive and 7 MuSK-Ab-negative patients) who underwent electrodiagnostic testing before and after a neostigmine test (NT). Results The frequency of intolerance to pyridostigmine bromide (PB) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (50% vs. 0%, respectively; p=0.044), while the maximum tolerable dose of PB was lower in the former (90 mg/day vs. 480 mg/day, p=0.023). The frequency of positive NT results was significantly lower in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (40% vs. 100%, p=0.035), while the nicotinic side effects of neostigmine were more frequent in the former (80% vs. 14.3%, p=0.015). Repetitive compound muscle action potentials (R-CMAPs) developed more frequently after NT in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (90% vs. 14.3%, p=0.004). The frequency of a high-frequency-stimulation-induced decrement-increment pattern (DIP) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (100% vs. 17.7%, p=0.003). Conclusions These results suggest that MuSK-Ab-positive MG patients exhibit unique and hyperactive responses to AChEIs. Furthermore, R-CMAP and DIP development on a standard AChEI dose may be a distinct neurophysiologic feature indicative of MuSK-Ab-positive MG. PMID:24829597

Shin, Ha Young; Park, Hyung Jun; Lee, Hyo Eun; Choi, Young-Chul

2014-01-01

87

Neuromyelitis Optica with NMO-IgG/Anti-AQP4 Antibody Positive: First Case Reported from Uttarakhand India  

PubMed Central

Neuromyelitis optica (also known as Devic’s disease) is an idiopathic, severe, demyelinating disease of the central nervous system that preferentially affects the optic nerve and spinal cord. The presence of a highly specific serum autoantibody marker (NMO-IgG) further differentiates neuromyelitis optica from multiple sclerosis and has helped to define a neuromyelitis optica spectrum of disorders. We present a case of 37-year-old man who has initially presented with transverse myelitis from which he recovered partially after treatment but later presented with bilateral optic neuritis. MRI brain revealed hyperintensity in bilateral optic nerves, periventricular area and also in the thalamic region. Diagnosis was confirmed by positive NMO – IgG/anti-AQP4 antibody. PMID:25177594

Mittal, Garima

2014-01-01

88

Prevalence and Risk Factors for Neutralizing Antibodies to Human Papillomavirus Types 16 and 18 in HIV-positive Men who have Sex with Men  

PubMed Central

Objective HPV vaccination is routinely recommended in HIV-positive MSM ? 26 years old. Levels of prior HPV exposure in older HIV-positive MSM are assumed to be too high to warrant routine HPV vaccination. However, little is known about the prevalence of and risk factors for neutralizing antibody seropositivity to HPV-16 or HPV-18, a key measure of prior exposure to these types. Methods Cross-sectional analysis of baseline visit for 296 HIV-positive MSM participating in a prospective cohort study of anal squamous intraepithelial lesions (ASIL) at a university-based research clinic. Participants completed a questionnaire detailing behaviors and medical history. Phlebotomy, anal cytology, HPV DNA testing with quantitation, and high resolution anoscopy with biopsy were performed. A pseudovirion-based neutralizing antibody (PBNA) assay was used to measure HPV-16 and HPV-18 neutralizing antibodies. Results 132/296 (45%) men were HPV-16-seropositive and 141/296 (48%) were HPV-18-seropositive. 175/296 (59%) of the men were positive for HPV-16 antibodies or DNA, and 167/296 (56%) were positive for HPV-18 antibodies or DNA. In multivariable analysis, HPV-16 seropositivity did not correlate with age, years of HIV positivity, CD4+ level or HIV viral load. Significant risk factors included HPV-16 DNA positivity with higher DNA levels (ptrend<.001) and higher number of receptive sexual partners in the last year (ptrend=.012). Conclusions A high proportion of HIV-positive MSM >26 years are DNA-negative and seronegative to HPV-16 and HPV-18 even when using a sensitive PBNA assay. Prospective studies are needed to determine the clinical- and cost-effectiveness of HPV vaccination in HIV-positive MSM > 26 years old. PMID:24231786

Sharma, Rachna; Efird, Jimmy T.; Chein, Aung; Holly, Elizabeth A.; Krajden, Mel; Berry, Michael J.; Darragh, Teresa M.; Jay, Naomi; Palefsky, Joel M.

2013-01-01

89

Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors  

PubMed Central

Background and aims: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. Patients: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. Results: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4–39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1–23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. Conclusion: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence. PMID:11772974

Roque-Afonso, A M; Feray, C; Samuel, D; Simoneau, D; Roche, B; Emile, J-F; Gigou, M; Shouval, D; Dussaix, E

2002-01-01

90

Identification of Novel HLA-A*0201-restricted epitopes in recent-onset type 1 diabetic subjects and antibody-positive relatives.  

PubMed

Cytotoxic T-lymphocytes (CTLs) are considered to be essential for beta-cell destruction in type 1 diabetes. However, few islet-associated peptides have been demonstrated to activate autoreactive CTLs from type 1 diabetic subjects. In an effort to identify novel epitopes, we used matrix-assisted algorithms to predict peptides of glial fibrillary acidic protein (GFAP), prepro-islet amyloid polypeptide (ppIAPP), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) that likely bind to HLA-A*0201 with a strong affinity and contain a COOH-terminal proteasomal cleavage site. Seven peptides stabilized HLA-A*0201 expression in binding assays and were used to stimulate peripheral blood mononuclear cells and were evaluated for granzyme B secretion. We found that 5 of 13 type 1 diabetic subjects and 4 of 6 antibody-positive relatives exhibited greater numbers of granzyme B-secreting cells in response to at least one putative epitope compared with healthy control subjects. The most prevalent responses in antibody-positive and type 1 diabetic subjects were to ppIAPP(9-17). Other peptides recognized by type 1 diabetic or antibody-positive subjects included GFAP(143-151), IGRP(152-160), and GFAP(214-222). These data implicate peptides of ppIAPP, GFAP, and IGRP as CTL epitopes for a heterogenous CD8(+) T-cell response in type 1 subjects and antibody-positive relatives. PMID:17065343

Standifer, Nathan E; Ouyang, Qin; Panagiotopoulos, Constadina; Verchere, C Bruce; Tan, Rusung; Greenbaum, Carla J; Pihoker, Catherine; Nepom, Gerald T

2006-11-01

91

Combination of novel HER2-targeting antibody 1E11 with trastuzumab shows synergistic antitumor activity in HER2-positive gastric cancer.  

PubMed

The synergistic interaction of two antibodies targeting the same protein could be developed as an effective anti-cancer therapy. Human epidermal growth factor receptor 2 (HER2) is overexpressed in 20-25% of breast and gastric cancer patients, and HER2-targeted antibody therapy using trastuzumab is effective in many of these patients. Nonetheless, improving therapeutic efficacy and patient survival is important, particularly in patients with HER2-positive gastric cancer. Here, we describe the development of 1E11, a HER2-targeted humanized monoclonal antibody showing increased efficacy in a highly synergistic manner in combination with trastuzumab in the HER2-overexpressing gastric cancer cell lines NCI-N87 and OE-19. The two antibodies bind to sub-domain IV of the receptor, but have non-overlapping epitopes, allowing them to simultaneously bind HER2. Treatment with 1E11 alone induced apoptosis in HER2-positive cancer cells, and this effect was enhanced by combination treatment with trastuzumab. Combination treatment with 1E11 and trastuzumab reduced the levels of total HER2 protein and those of aberrant HER2 signaling molecules including phosphorylated HER3 and EGFR. The synergistic antitumor activity of 1E11 in combination with trastuzumab indicates that it could be a novel potent therapeutic antibody for the treatment of HER2-overexpressing gastric cancers. PMID:25306393

Ko, Bong-Kook; Lee, Sook-Yeon; Lee, Young-Ha; Hwang, In-Sik; Persson, Helena; Rockberg, Johan; Borrebaeck, Carl; Park, Dongeun; Kim, Kyu-Tae; Uhlen, Mathias; Lee, Jong-Seo

2015-02-01

92

Clonal expansion of IgA-positive plasma cells and axon-reactive antibodies in MS lesions.  

PubMed

Immunoglobulin A (IgA), the predominant immunoglobulin class in mucosal secretions, has been found in the cerebrospinal fluid of patients with multiple sclerosis (MS). In this study we examined the infiltration of clonally expanded IgA plasma cells in lesions of MS brains. Sequences of complementarity-determining region 3 of IgA variable heavy chain (V(H)) genes demonstrated the clonal expansion of IgA-bearing plasma cells in MS lesions. Somatic mutations and ongoing intra-clonal mutations occurred in their V(H) genes. Immunohistochemical study demonstrated infiltration of dimer and polymer IgA1- and A2-positive plasma cells in perivascular spaces, in the parenchyma of MS lesions, and in the adjacent white matter. Double immunofluorescence staining showed binding of IgA antibody on axons and walls of microvessels in the areas of chronic active and inactive demyelination. Bielshowsky's silver impregnation revealed axonal damage in these areas. These findings suggest that IgA in the CNS are localized on axons in lesions and may contribute to axonal damage in MS. PMID:16099056

Zhang, Yiping; Da, Reng-Rong; Hilgenberg, Lutz G; Tourtellotte, Wallace W; Sobel, Raymond A; Smith, Martin A; Olek, Michael; Nagra, Rashed; Sudhir, Gupta; van den Noort, Stanley; Qin, Yufen

2005-10-01

93

Maternal HLA Panel Reactive Antibodies in Early Gestation Positively Correlates with Chronic Chorioamnionitis: Evidence in Support of the Chronic Nature of Maternal Anti-fetal Rejection  

PubMed Central

Problem Maternal tolerance of the fetus is essential for viviparity, yet anti-fetal rejection occurs in several pregnancy complications. Chronic chorioamnionitis (CCA) is a feature of anti-fetal cellular rejection. There is a robust association between CCA and maternal seropositivity for anti-HLA panel reactive antibodies (PRA) at the time of delivery. This longitudinal study was performed to assess maternal HLA PRA status in early gestation and the temporal evolution of maternal HLA PRA in the context of CCA and thereby to determine whether HLA PRA during the course of pregnancy is useful for the detection of anti-fetal rejection. Method of Study Maternal sera obtained before 16 weeks of gestation and at delivery were analyzed for HLA panel reactive antibodies (PRA) in cases with (N=100) and without (N=150) CCA. Results IgG but not IgM HLA class I and II PRA positivity at delivery was higher in cases with CCA than in those without CCA. IgG HLA class I PRA positivity before 16 weeks of gestation was higher in cases with CCA than in those without (30.3% vs. 13.3%; p=0.001). Positive conversion (negative HLA PRA before 16 weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was significantly associated with CCA. Fetal HLA class I antigen-specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized to HLA class I antigens before 16 weeks of gestation. Conclusion Positive maternal HLA PRA before 16 weeks of gestation and the temporal evolution of maternal HLA PRA are associated with the presence of CCA at the time of delivery. Maternal IgG HLA PRA has potential to be a monitoring tool of anti-fetal rejection. Furthermore, the findings herein indicate that subsets of fetuses are exposed to alloimmune HLA antibodies for months, especially in cases with CCA. PMID:21951517

Lee, JoonHo; Romero, Roberto; Xu, Yi; Kim, Jung-Sun; Park, Ji Young; Kusanovic, Juan Pedro; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.; Kim, Chong Jai

2011-01-01

94

Involvement of branched units at position 6 in the reactivity of a unique variety of beta-D-glucan from Aureobasidium pullulans to antibodies in human sera.  

PubMed

We recently determined the structure of a unique type of 1,3-beta-D-glucan obtained from Aureobasidium pullulans (AP-FBG) and found that it reacted with the antibodies in human sera. The reactivity of AP-FBG to the antibodies was stronger than that of 1,3-beta-D-glucan obtained Grifola frondosa (GRN) but weaker than that of 1,3-beta-D-glucan from Candida albicans (CSBG). Here, we demonstrated that AP-FBG reacted to IgG antibodies, especially those of the subclasses IgG2, IgG1, and IgG3, in human sera. Moreover, the results of competitive enzyme-linked immunosorbent assays (ELISAs) using various glucan competitors showed that these IgGs recognized branched chains at position 6. This is the first study to report that the branched chains at position 6 of beta-D-glucan strongly contribute to its recognition by antibodies in human sera. This high reactivity of AP-FBG to human IgG could be advantageous for the use of this glucan in medicine, e.g., as an immunostimulatory agent. PMID:19352033

Tada, Rui; Tanioka, Asuka; Ishibashi, Ken-ichi; Adachi, Yoshiyuki; Tsubaki, Kazufumi; Ohno, Naohito

2009-04-23

95

Increased detection of Sin Nombre hantavirus RNA in antibody-positive deer mice from Montana, USA: evidence of male bias in RNA viremia.  

PubMed

Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood early in the infection cycle, while sequestered long term in various host organs. Field studies of North American deer mice (Peromyscus maniculatus), the natural reservoir of Sin Nombre hantavirus, have shown that viral RNA can be transiently detected well past the early acute infection stage, but only in the minority of infected mice. Here, using a non-degenerate RT-PCR assay optimized for SNV strains known to circulate in Montana, USA, we show that viral RNA can be repeatedly detected on a monthly basis in up to 75% of antibody positive deer mice for periods up to 3-6 months. More importantly, our data show that antibody positive male deer mice are more than twice as likely to have detectable SNV RNA in their blood as antibody positive females, suggesting that SNV-infected male deer mice are more likely to shed virus and for longer periods of time. PMID:24064796

Bagamian, Karoun H; Towner, Jonathan S; Mills, James N; Kuenzi, Amy J

2013-09-01

96

High Levels of Soluble Ctla-4 Are Present in Anti-Mitochondrial Antibody Positive, but Not in Antibody Negative Patients with Primary Biliary Cirrhosis  

PubMed Central

Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease frequently characterized by anti-mitochondrial autoantibodies (AMA). A minority of patients are AMA-negative. Cytotoxic-T-Lymphocyte-Antigen-4 (CTLA-4) is a surface molecule expressed on activated T-cells delivering a critical negative immunoregulatory signal. A soluble form of CTLA-4 (sCTLA-4) has been detected at high concentrations in several autoimmune diseases, and its possible functional meaning has been suggested. We aimed to evaluate sCTLA-4 concentration in sera of patients with PBC and to correlate it to immunological abnormalities associated with the disease. Blood samples were collected from 82 PBC-patients diagnosed according to international criteria (44 AMA-positive/MIT3-positive and 38 AMA-negative-MIT3-negative), and 65 controls. sCTLA-4 levels were evaluated by ELISA and Western blot. Increased sCTLA-4 concentrations were found in all AMA-positive PBC-patients, but in none of the AMA-negative ones, nor in normal controls or in controls with unrelated liver diseases. sCTLA-4 presence was associated with autoantibodies against MIT3, but not with nuclear autoantibodies (sp100, gp210). This is the first study to demonstrate that levels of sCTLA-4 are elevated in sera of PBC patients. However, they are clearly restricted to patients with AMA positivity, suggesting an immunological difference with respect to AMA-negative ones. PMID:25383768

Saverino, Daniele; Pesce, Giampaola; Antola, Princey; Porcelli, Brunetta; Brusca, Ignazio; Villalta, Danilo; Tampoia, Marilina; Tozzoli, Renato; Tonutti, Elio; Alessio, Maria Grazia; Bagnasco, Marcello; Bizzaro, Nicola

2014-01-01

97

Elevated Anticardiolipin Antibody Titer Is a Stroke Risk Factor in a Multiethnic Population Independent of Isotype or Degree of Positivity  

Microsoft Academic Search

Background and Purpose—Previous studies have produced conflicting results regarding the putative association between anticardiolipin antibodies (aCL) and infarction in the general stroke population. These inconsistencies may be a function of sample size and methodological differences among the studies. The purpose of the present study, the largest case-control study of this issue to date, was to assess aCL status as an

Jacob H. Rand; Xiao-Xuan Wu; Jesse Weinberger; Deborah R. Horowitz; Martin E. Goldman; James H. Godbold

98

T-Cell and Antibody Responses to Mycobacterial Antigens in Tuberculin Skin-Test-Positive Bos indicus and Bos taurus Cattle in Ethiopia.  

PubMed

Higher IFN-? responses to mycobacterial antigens were observed in Bos taurus (Holsteins) than in Bos indicus (Zebu) cattle which could due to differences in antigen recognition profiles between the two breeds. The present study was conducted to evaluate mycobacterial antigen recognition profiles of the two breeds. Twenty-three mycobacterial antigens were tested on 46 skin test positive (24 Zebu and 22 Holstein) using enzyme-linked immunospot assay (ELISPOT) and multiple antigen print immunoassay (MAPIA). Herds from which the study cattle obtained were tested for Fasciola antibody. The T cells from both breeds recognized most of the mycobacterial antigens at lower and comparable frequencies. However, antigens such as CFP-10, ESAT-6, Rv0287, Rv0288, MPB87, Acr-2, Rv3616c, and Rv3879c were recognized at higher frequencies in zebu while higher frequencies of T cell responses were observed to Hsp65 in both breeds. Furthermore, comparable antibody responses were observed in both breeds; MPB83 being the sero-dominant antigen in both breeds. The prevalence of Fasciola antibody was 81% and similar in both breeds. This piece of work could not lead to a definitive conclusion if there are differences in mycobacterial recognition profiles between the two breeds warranting for further similar studies using sound sample size from the two breeds. PMID:22685689

Ameni, Gobena; Cockle, Paul; Lyashchenko, Konstantin; Vordermeier, Martin

2012-01-01

99

T-Cell and Antibody Responses to Mycobacterial Antigens in Tuberculin Skin-Test-Positive Bos indicus and Bos taurus Cattle in Ethiopia  

PubMed Central

Higher IFN-? responses to mycobacterial antigens were observed in Bos taurus (Holsteins) than in Bos indicus (Zebu) cattle which could due to differences in antigen recognition profiles between the two breeds. The present study was conducted to evaluate mycobacterial antigen recognition profiles of the two breeds. Twenty-three mycobacterial antigens were tested on 46 skin test positive (24 Zebu and 22 Holstein) using enzyme-linked immunospot assay (ELISPOT) and multiple antigen print immunoassay (MAPIA). Herds from which the study cattle obtained were tested for Fasciola antibody. The T cells from both breeds recognized most of the mycobacterial antigens at lower and comparable frequencies. However, antigens such as CFP-10, ESAT-6, Rv0287, Rv0288, MPB87, Acr-2, Rv3616c, and Rv3879c were recognized at higher frequencies in zebu while higher frequencies of T cell responses were observed to Hsp65 in both breeds. Furthermore, comparable antibody responses were observed in both breeds; MPB83 being the sero-dominant antigen in both breeds. The prevalence of Fasciola antibody was 81% and similar in both breeds. This piece of work could not lead to a definitive conclusion if there are differences in mycobacterial recognition profiles between the two breeds warranting for further similar studies using sound sample size from the two breeds. PMID:22685689

Ameni, Gobena; Cockle, Paul; Lyashchenko, Konstantin; Vordermeier, Martin

2012-01-01

100

Nuclear Energy. It is not a solution, it is a problem The Mediterranean Antinuclear Watch (MANW) is a non -  

E-print Network

Nuclear Energy. It is not a solution, it is a problem #12;The Mediterranean Antinuclear Watch (MANW - called "peaceful use" of nuclear energy as well as the production and proliferation of nuclear weapons pose. #12;Nuclear energy renaissance Twenty two years after the accident in Chernobyl NPP. Energy

101

Evaluation of heterophilic antibody blocking agents in reducing false positive interference in immunoassays for IL-17AA, IL-17FF, and IL-17AF.  

PubMed

IL-17AA, IL-17FF, and IL-17AF are proinflammatory cytokines that have been implicated in the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA). In order to measure the levels of these cytokines in synovial fluid and serum samples from RA patients, immunoassays specific for IL-17AA, FF, and AF were developed. Although these assays could tolerate up to 50% pooled normal human serum, false positive reactivity was problematic in patient samples suggesting interference from heterophilic antibodies. We therefore evaluated the ability of several commercially available heterophilic antibody blocking agents to reduce false positive reactivity by testing them against samples that were confirmed as false positives in the IL-17AA, FF, and AF assays. Several of the blockers performed well, including HBR-1, HBR-9, HBR-11, HBR-Plus, Serum Cytokine Assay Diluent, and IIR. We chose to move forward using IIR blocker for sample analysis and verified that IIR had no effect on the assay standard curves and did not affect IL-17 quantitation in plasma from ex vivo stimulated human whole blood. IL-17FF and IL-17AF were below the limits of quantitation of the assays (12.3 and 10.5pg/ml, respectively) in synovial fluid and serum samples from patients with RA and osteoarthritis (OA). For the more sensitive IL-17AA assay (1.6pg/ml limit of quantitation), low levels of IL-17AA were measurable in 48% of RA synovial fluid samples (mean, 7.9pg/ml; median, <1.6pg/ml; range, <1.6-29.7pg/ml; n=23) but not in synovial fluid from patients with OA (n=33). For serum samples, however, IL-17AA was below the limit of detection for both RA and OA patients. When these same serum samples were analyzed in the absence of a heterophilic antibody blocker, false positive reactivity yielded apparent mean IL-17AA levels of 43.3pg/ml (28% positive; n=50) and 14.8pg/ml (12% positive; n=50) for RA and OA patients, respectively, results that could potentially be interpreted as consistent with disease biology. These studies demonstrate the importance of ensuring that HAb interference is well controlled, particularly when measuring low concentrations of cytokines in samples from patients with autoimmune disease. PMID:20833179

DeForge, Laura E; Loyet, Kelly M; Delarosa, Donnie; Chinn, Jason; Zamanian, Fojan; Chuntharapai, Anan; Lee, James; Hass, Phil; Wei, Nathan; Townsend, Michael J; Wang, Jianyong; Wong, Wai Lee T

2010-10-31

102

Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.  

PubMed

Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ? 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ? 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days. PMID:22261239

Litster, Annette; Nichols, Jamieson; Volpe, Allison

2012-05-25

103

Seroprevalence of other antibodies (herpes, CMV, rubella, varicella, hepatitis B and C, syphilis, chlamydia, mumps, toxoplasmosis) in HIV-positive patients.  

PubMed

We attempted to determine the seropositivity of HIV-positive patients to other antibodies (herpes, CMV, rubella, varicella, hepatitis B, hepatitis C, syphilis, chlamydia, mumps, toxoplasmosis). The study was carried out at the Prenatal Diagnosis and Therapy Centre of a Tertiary Hospital in Lagos, Nigeria. A total of 70 patients (50 females and 20 males) attending the centre between June 1997 and December 2005 who were screened and found to be HIV-seropositive were further screened for herpes simplex IgG/IgM, CMV IgG/IgM, rubella IgG/IgM, varicella IgG/IgM, mumps IgG/IgM, toxoplasmosis IgG/IgM, chlamydia IgG/IgM, hepatitis B and hepatitis C IgG/IgM using ELISA kits and syphilis (THPA) using the HAE method. Our study showed that a large number of HIV-positive patients are carriers of other antibodies and should be screened for them before therapy. PMID:21793283

Ajayi, G O; Omilabu, S A; Alamu, D; Balogun, Y; Badaru, S

2011-01-01

104

Placental Hofbauer cells assemble and sequester HIV-1 in tetraspanin-positive compartments that are accessible to broadly neutralizing antibodies  

PubMed Central

Introduction Within monocyte-derived macrophages, HIV-1 accumulates in intracellular virus-containing compartments (VCCs) that are inaccessible to the external environment, which implicate these cells as latently infected HIV-1 reservoirs. During mother-to-child transmission of HIV-1, human placental macrophages (Hofbauer cells (HCs)) are viral targets, and have been shown to be infected in vivo and sustain low levels of viral replication in vitro; however, the risk of in utero transmission is less than 7%. The role of these primary macrophages as viral reservoirs is largely undefined. The objective of this study is to define potential sites of viral assembly, accumulation and neutralization in HCs given the pivotal role of the placenta in preventing HIV-1 infection in the mother-infant dyad. Methods Term placentae from 20 HIV-1 seronegative women were obtained following caesarian section. VCCs were evaluated by 3D confocal and electron microscopy. Colocalization R values (Pearson's correlation) were quantified with colocalization module of Volocity 5.2.1. Replication kinetics and neutralization studies were evaluated using p24 ELISA. Results We demonstrate that primary HCs assemble and sequester HIV-1BaL in intracellular VCCs, which are enriched in endosomal/lysosomal markers, including CD9, CD81, CD63 and LAMP-1. Following infection, we observed HIV-1 accumulation in potentially acidic compartments, which stained intensely with Lysotracker-Red. Remarkably, these compartments are readily accessible via the cell surface and can be targeted by exogenously applied small molecules and HIV-1-specific broadly neutralizing antibodies. In addition, broadly neutralizing antibodies (4E10 and VRC01) limited viral replication by HIV-1-infected HCs, which may be mediated by Fc?RI. Conclusions These findings suggest that placental HCs possess intrinsic adaptations facilitating unique sequestration of HIV-1, and may serve as a protective viral reservoir to permit viral neutralization and/or antiretroviral drug entry in utero. PMID:25623930

Johnson, Erica L; Chu, Hin; Byrareddy, Siddappa Nagadenahalli; Spearman, Paul; Chakraborty, Rana

2015-01-01

105

Risk factors for herds to test positive for Mycobacterium avium ssp. paratuberculosis-antibodies with a commercial milk enzyme-linked immunosorbent assay (ELISA) in Ontario and western Canada  

PubMed Central

The objectives of this study were to identify risk factors associated with i) a Mycobacterium avium subsp. paratuberculosis (MAP)-antibody milk enzyme-linked immunosorbent assay (MAP milk ELISA)-positive herd status, and ii) the within-herd MAP milk ELISA-positive prevalence in Canadian dairy herds. This prospective cohort study was conducted between 2005 and 2009 on 226 herds in Ontario and western Canada, which participated in a voluntary risk assessment (RA)-based Johne’s disease control program. Two MAP milk ELISA and risk assessments and a previsit survey were available per herd. The overall farm RA scores alone could not be used to predict whether a herd would test positive for MAP antibodies. However, the results of this study indicated that increasing the likelihood of exposing calves to MAP through certain management practices, as assessed with the RA, increased the likelihood of a herd being test-positive for MAP antibodies. PMID:23450860

Sorge, Ulrike S.; Lissemore, Kerry; Godkin, Ann; Jansen, Jocelyn; Hendrick, Steven; Wells, Scott; Kelton, David F.

2012-01-01

106

False-positive imaging of In-111 labeled monoclonal antibody conjugate CYT-103 in a patient with metastatic colorectal carcinoma.  

PubMed

In-111 satumomab whole-body imaging is used in the evaluation of patients with colorectal carcinoma. The authors report a case of false-positive In-111 localization in a nonfunctional adrenal adenoma in a patient with metastatic colon carcinoma. PMID:8565379

Bhatia, M; Baron, P L; Alderman, D F; Gordon, L

1995-11-01

107

Presence of IgG Anti-gp160/120 Antibodies Confers Higher HIV Capture Capacity to Erythrocytes from HIV-Positive Individuals  

PubMed Central

Background HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available. Methodology/Principal Findings IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho?=?0.022, p?=?0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals. Conclusions/Significance Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes. PMID:23049866

Garcia, Maria Noé; dos Ramos Farias, Maria Sol; Fazzi, Lucia; Grasso, Daniel; Rabinovich, Roberto Daniel; Ávila, Maria Mercedes

2012-01-01

108

Nuclear energy in postwar Japan and anti-nuclear movements in the 1950s.  

PubMed

The atomic bombings of Hiroshima and Nagasaki in August 1945 revealed the most destructive power to-date of man-made weapons. Their impact was so great that Japanese scientists thought that a bigger disaster could be prevented only if war was abolished. Thus they welcomed the international control of atomic energy. It was, however, only after the occupation that the Japanese general public began to learn about the horror of these atomic disasters due to the censorship imposed by the occupational forces. The hydrogen bomb test by the US in the Bikini atoll on March 1, 1954 renewed fears of nuclear weapons. The crew of a Japanese fishing vessel, the "Daigo Fukuryu Maru" (Lucky Dragon No. 5) suffered from exposure to radiation from the test. Even after the incident the US did not stop nuclear tests which continued to radioactively contaminate fish and rains in Japan. As a result, the petition movement for the ban of nuclear trials suddenly spread all over the country. By the summer of 1955 the number of the signatures grew to more than one third of Japan's population at the time. Under the strong influence of anti-nuclear Japanese public opinion the Science Council of Japan announced the so-called three principles of atomic energy: "openness," "democracy," and "independence" to ensure atomic energy was used for peaceful uses only. These principles were included in the Atomic Energy Basic Law established in December 1955. With this law, military uses of nuclear energy were strictly forbidden. PMID:20521422

Yamazaki, Masakatsu

2009-01-01

109

A Successful Bilateral Lung Transplantation in a Patient with High Panel Reactive Antibody and Positive Cross Matching  

PubMed Central

A 44-year-old pregnant female patient gave stillbirth while being treated for pneumonia. She developed acute respiratory failure, which resulted in mechanical ventilator support. Diagnostic lung biopsy revealed a cryptogenic organizing pneumonia. The patient’s condition deteriorated and a venous-venous extracorporeal membrane oxygenation was placed. She was listed for lung transplantation. Because of her worsening condition lung transplantation was performed despite positive cross matching result. She was treated with rituximab, intravenous immunoglobulin, and plasmapheresis and recovered without event. There is no sign of rejection at the time of last follow-up. PMID:25207257

Bok, Jin San; Jun, Jae Hyun; Lee, Hyun Joo; Park, In Kyu; Kang, Chang Hyun; Yang, Jaeseok; Kim, Young Tae

2014-01-01

110

A successful bilateral lung transplantation in a patient with high panel reactive antibody and positive cross matching.  

PubMed

A 44-year-old pregnant female patient gave stillbirth while being treated for pneumonia. She developed acute respiratory failure, which resulted in mechanical ventilator support. Diagnostic lung biopsy revealed a cryptogenic organizing pneumonia. The patient's condition deteriorated and a venous-venous extracorporeal membrane oxygenation was placed. She was listed for lung transplantation. Because of her worsening condition lung transplantation was performed despite positive cross matching result. She was treated with rituximab, intravenous immunoglobulin, and plasmapheresis and recovered without event. There is no sign of rejection at the time of last follow-up. PMID:25207257

Bok, Jin San; Jun, Jae Hyun; Lee, Hyun Joo; Park, In Kyu; Kang, Chang Hyun; Yang, Jaeseok; Kim, Young Tae

2014-08-01

111

Antibody-mediated rejection after adult living-donor liver transplantation triggered by positive lymphocyte cross-match combination  

PubMed Central

A 46-year-old female suffering from liver cirrhosis was referred to us for living-donor liver transplantation (LDLT). Pre-transplant lymphocyte cross-match tests were positive. The recipient showed immunoreactivity against donor human leukocyte antigen (HLA) Class I antigens, a finding confirmed by flow cytometry. Additional tests confirmed donor-specific lymphocyte immunoreactivity against HLA B 55. As no other suitable donor was available, we performed LDLT coupled with splenectomy, despite the positive cross-match. Tacrolimus, methylprednisolone and mycophenolate mofetil were used postoperatively for immunosuppression. The postoperative course was uneventful until Day 3 when blood tests showed disorders in liver function and the patient’s condition suddenly worsened. Although intensive care (including plasma exchange) was given, her condition continued to deteriorate. Flow cytometry initially showed that immunoreactivity against Class I antigens was down-regulated immediately after LDLT, but further testing showed that it had increased again. We diagnosed humoral rejection based on clinical, immunological and histopathological findings and suggest that this was mediated by an immune response to donor-specific antigens. The patient experienced multi-organ failure and died on post-operative Day 9. PMID:24714061

Hori, Tomohide; Egawa, Hiroto; Uemoto, Shinji

2012-01-01

112

Anti–citrullinated protein antibody positivity correlates with cartilage damage and proteoglycan levels in patients with rheumatoid arthritis in the hand joints.  

PubMed

Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (?3 years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA. PMID:25185889

Renner, Nina; Krönke, Gerhard; Rech, Jürgen; Uder, Michael; Janka, Rolf; Lauer, Lars; Paul, Dominik; Herz, Barbara; Schlechtweg, Philipp; Hennig, Friedrich Frank; Schett, Georg; Welsch, Götz

2014-12-01

113

Discrimination between the main activating and inhibitory killer cell immunoglobulin-like receptor positive natural killer cell subsets using newly characterized monoclonal antibodies  

PubMed Central

Natural killer (NK) cells are key components of the innate anti-viral and anti-tumour immune responses. NK cell function is regulated by the interaction of killer cell immunoglobulin-like receptors (KIR) with human leucocyte antigen (HLA) class I molecules. In this study, we report on the generation of KIR-specific antibodies allowing for discrimination between activating and inhibitory KIR. For this purpose, BALB/c mice were immunized with human KIR2DS2 recombinant protein. The precise specificity of KIR2DS2-specific clones was determined on KIR-transfected BW cells and KIR-genotyped NK cells. When used in combination with EB6 (KIR2DL1/2DS1) or GL183 (KIR2DL2/2DL3/2DS2), two KIR-specific monoclonal antibodies (mAbs), 8C11 (specific for KIR2DL1/2DL2/2DL3/2DS2) and 1F12 (specific for KIR2DL3/2DS2), discriminated activating KIR2DS1 (8C11? EB6+) from inhibitory KIR2DL1 (8C11+ GL183?) and KIR2DL2 (1F12? GL183+), while excluding the main HLA-Cw-specific KIR. Using these mAbs, KIR2DS1 was shown to be expressed on the surface of NK cells from all individuals genotyped as KIR2DS1+ (n = 23). Moreover, KIR2DS1 and KIR2DL1 were independently expressed on NK cells. We also determined the amino acid position recognized by the 8C11 and 1F12 mAbs, which revealed that some KIR2DL1 allele-encoded proteins are not recognized by 8C11. Because most available anti-KIR mAbs recognize both inhibitory and activating forms of KIR, these newly characterized antibodies should help assess the expression of activating and inhibitory KIR and their functional relevance to NK biology. PMID:19740374

David, Gaëlle; Morvan, Maelig; Gagne, Katia; Kerdudou, Nolwenn; Willem, Catherine; Devys, Anne; Bonneville, Marc; Folléa, Gilles; Bignon, Jean-Denis; Retière, Christelle

2009-01-01

114

Endogenous interleukin 6 production in multiple myeloma patients treated with chimeric monoclonal anti-IL6 antibodies indicates the existence of a positive feed-back loop.  

PubMed Central

In vitro as well as in vivo observations have shown that IL6 plays a key role in the pathogenesis of multiple myeloma. Therefore we started a phase I/II dose escalating study with chimeric monoclonal anti-IL6 antibodies (cMab) in multiple myeloma (MM) patients resistant to second-line chemotherapy. Here we describe the pharmacological data as well as a new method for calculating the endogenous IL6 production. The cMab (CLB IL6/8; Kd: 6.25 x 10(-12) M) was given in two cycles of 14 daily infusions, starting on day 1 and day 28. Daily dose: 5 mg in patients 1-3, 10 mg in patients 4-6, and 20 mg in patients 7-9 (total dose 140, 280, and 560 mg of anti-IL6, respectively). Using the pharmacokinetic data of free IL6 and the binding characteristics of the cMab, the endogenous IL6 production could be calculated from day to day using a one-compartment open model. The median half-life time of this antibody was 17.6 d. No human antichimeric antibodies were induced. Pre-treatment median endogenous IL6 production in the MM patients was 60 micrograms/d (range 13.8-230; normal controls < 7 micrograms/d). During treatment with anti-IL6 cMabs, the endogenous IL6 production immediately decreased in all patients to below 3 micrograms/d and never reached the pre-treatment value during the treatment period, except in two patients who developed an active infection, resulting in an IL6 production of 128 and 1,208 micrograms/d, respectively. We concluded that in MM patients endogenous IL6 production is 2-30 times higher than in healthy individuals. The anti-IL6 cMab strongly suppress this endogenous IL6 production, probably by blocking a positive feed-back loop, but this cMab does not prevent infection-induced IL6 production. The chimeric anti-IL6 Mabs have a long half-life time, a low immunogenicity, and are able to block IL6-dependent processes in vivo. PMID:8823310

van Zaanen, H C; Koopmans, R P; Aarden, L A; Rensink, H J; Stouthard, J M; Warnaar, S O; Lokhorst, H M; van Oers, M H

1996-01-01

115

Quantitative Hepatitis B Core Antibody Level Is a New Predictor for Treatment Response In HBeAg-positive Chronic Hepatitis B Patients Receiving Peginterferon  

PubMed Central

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ?30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy. PMID:25553110

Hou, Feng-Qin; Song, Liu-Wei; Yuan, Quan; Fang, Lin-Lin; Ge, Sheng-Xiang; Zhang, Jun; Sheng, Ji-Fang; Xie, Dong-Ying; Shang, Jia; Wu, Shu-Huan; Sun, Yong-Tao; Wei, Shao-Feng; Wang, Mao-Rong; Wan, Mo-Bin; Jia, Ji-Dong; Luo, Guang-Han; Tang, Hong; Li, Shu-Chen; Niu, Jun-Qi; Zhou, Wei-dong; Sun, Li; Xia, Ning-Shao; Wang, Gui-Qiang

2015-01-01

116

Quantitative Hepatitis B Core Antibody Level Is a New Predictor for Treatment Response In HBeAg-positive Chronic Hepatitis B Patients Receiving Peginterferon.  

PubMed

A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ?30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy. PMID:25553110

Hou, Feng-Qin; Song, Liu-Wei; Yuan, Quan; Fang, Lin-Lin; Ge, Sheng-Xiang; Zhang, Jun; Sheng, Ji-Fang; Xie, Dong-Ying; Shang, Jia; Wu, Shu-Huan; Sun, Yong-Tao; Wei, Shao-Feng; Wang, Mao-Rong; Wan, Mo-Bin; Jia, Ji-Dong; Luo, Guang-Han; Tang, Hong; Li, Shu-Chen; Niu, Jun-Qi; Zhou, Wei-Dong; Sun, Li; Xia, Ning-Shao; Wang, Gui-Qiang

2015-01-01

117

Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test  

PubMed Central

Background Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). Methods We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. Results We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. Conclusion In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy. PMID:24551116

Hommel, Benjamin; Charuel, Jean-Luc; Jaureguiberry, Stéphane; Arnaud, Laurent; Courtin, Regis; Kassab, Petra; Prendki, Virginie; Paris, Luc; Ghillani-Dalbin, Pascale; Thellier, Marc; Caumes, Eric; Amoura, Zahir; Mazier, Dominique; Musset, Lucile; Buffet, Pierre; Miyara, Makoto

2014-01-01

118

Antithyroglobulin antibody  

MedlinePLUS

Antithyroglobulin antibody is a test to measure antibodies to a protein called thyroglobulin, which is found in ... This test helps detect possible thyroid problems. ... system. Such antibodies are more likely to appear after thyroid ...

119

CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies.  

PubMed

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.2 or 1.8?mg/kg intravenously) were administered to 56 patients with CD30-positive hematologic malignancies. Each patient also received either a sensitive CYP3A substrate (midazolam), an effective inducer (rifampin), or a strong inhibitor (ketoconazole). Brentuximab vedotin did not affect midazolam exposures. ADC exposures were unaffected by concomitant rifampin or ketoconazole; however, MMAE exposures were lower with rifampin and higher with ketoconazole. The short-term safety profile of brentuximab vedotin in this study was generally consistent with historic clinical observations. The most common adverse events were nausea, fatigue, diarrhea, headache, pyrexia, and neutropenia. Over a 1-week period, ?23.5% of intact MMAE was recovered after administration of brentuximab vedotin; all other species were below the limit of quantitation. The primary excretion route is via feces (median 72% of the recovered MMAE). These results suggest that brentuximab vedotin (1.8 mg/kg) and MMAE are neither inhibitors nor inducers of CYP3A; however, MMAE is a substrate of CYP3A. PMID:23754575

Han, Tae H; Gopal, Ajay K; Ramchandren, Radhakrishnan; Goy, Andre; Chen, Robert; Matous, Jeffrey V; Cooper, Maureen; Grove, Laurie E; Alley, Stephen C; Lynch, Carmel M; O'Connor, Owen A

2013-08-01

120

CYP3A-mediated drug-drug interaction potential and excretion of brentuximab vedotin, an antibody-drug conjugate, in patients with CD30-positive hematologic malignancies  

PubMed Central

Brentuximab vedotin is an antibody-drug conjugate (ADC) that selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells. This study evaluated the CYP3A-mediated drug-drug interaction potential of brentuximab vedotin and the excretion of MMAE. Two 21-day cycles of brentuximab vedotin (1.2 or 1.8 mg/kg intravenously) were administered to 56 patients with CD30-positive hematologic malignancies. Each patient also received either a sensitive CYP3A substrate (midazolam), an effective inducer (rifampin), or a strong inhibitor (ketoconazole). Brentuximab vedotin did not affect midazolam exposures. ADC exposures were unaffected by concomitant rifampin or ketoconazole; however, MMAE exposures were lower with rifampin and higher with ketoconazole. The short-term safety profile of brentuximab vedotin in this study was generally consistent with historic clinical observations. The most common adverse events were nausea, fatigue, diarrhea, headache, pyrexia, and neutropenia. Over a 1-week period, ~23.5% of intact MMAE was recovered after administration of brentuximab vedotin; all other species were below the limit of quantitation. The primary excretion route is via feces (median 72% of the recovered MMAE). These results suggest that brentuximab vedotin (1.8 mg/kg) and MMAE are neither inhibitors nor inducers of CYP3A; however, MMAE is a substrate of CYP3A. PMID:23754575

Han, Tae H.; Gopal, Ajay K.; Ramchandren, Radhakrishnan; Goy, Andre; Chen, Robert; Matous, Jeffrey V.; Cooper, Maureen; Grove, Laurie E.; Alley, Stephen C.; Lynch, Carmel M.; O’Connor, Owen A.

2013-01-01

121

Connective tissue disease features after thallium poisoning.  

PubMed

We present 5 patients in whom thallium poisoning (1) mimicked systemic lupus erythematosus (SLE) with positive antinuclear antibodies; (2) caused a SLE-like illness with positive antinuclear antibodies and rheumatoid factor that was followed by a persistent chronic polyarthritis; (3) mimicked SLE with negative antinuclear antibodies and no residual disease; (4) caused arthralgia, Raynaud's phenomenon and palmar erythema with negative antinuclear antibodies followed by keratoconjunctivitis sicca; and (5) triggered the onset of SLE with diffuse proliferative glomerulonephritis. Although the notion exists that thallium poisoning may simulate seronegative SLE, these associations between connective tissue diseases and thallium poisoning have not been previously recorded. PMID:2787403

Alarcón-Segovia, D; Amigo, M C; Reyes, P A

1989-02-01

122

A case of systemic lupus erythematosus with postpartum hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome and concomitant high phosphatidylserine-dependent anti-prothrombin antibody levels.  

PubMed

In August 1994, a 19-year-old woman presented to her dermatologist with a slight fever, arthralgia, and a butterfly rash. Discoid lupus erythematosus was suspected, and serological testing yielded positive results for antinuclear antibody. She was diagnosed with systemic lupus erythematosus without organ failure and was treated with only nonsteroidal antiinflammatory drugs. She became pregnant in June 2001, at age 26. In November her obstetrician noted that she had severe hypertension, edema of the low limbs, and proteinuria. On admission, she was diagnosed with severe preeclampsia, and cesarean section was performed. On hospital day 3 the patient developed sudden epigastric pain and vomiting. Laboratory tests revealed thrombocytopenia, liver dysfunction, and microangiopathic hemolytic anemia, leading to a diagnosis of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Plasma exchange was performed for 5 days. The thrombocytopenia, liver dysfunction, and proteinuria diminished quickly. Later testing revealed a high titer of plasma phosphatidylserine-dependent anti-prothrombin antibody. This case is useful for exploring the relations between SLE, HELLP syndrome, and anti-prothrombin antibody. PMID:17143701

Yamamoto, Motohisa; Nojima, Masahiro; Ohara, Mikiko; Suzuki, Chisako; Naishiro, Yasuyoshi; Itoh, Yoshiyuki; Yamamoto, Hiroyuki; Takahashi, Hiroki; Kitajima, Yoshimori; Endo, Toshiaki; Imai, Kohzoh

2004-01-01

123

The immunohistochemical expression profile of osteopontin in normal human tissues using two site-specific antibodies reveals a wide distribution of positive cells and extensive expression in the central and peripheral nervous systems.  

PubMed

To elucidate the cellular distribution of osteopontin (OPN) in normal human tissues, we undertook immunohistochemistry using two site-specific OPN antibodies. The 10A16 monoclonal antibody was raised against the amino acid sequence just downstream of the thrombin cleavage site, while the O-17 polyclonal antibody was raised against the N-terminal peptide. Each antibody has been confirmed previously to react with both whole OPN and its relevant fragments. The expression pattern for these two antibodies was similar in distribution. In addition, we also identified expression in Ebner's gland, type II pneumocytes, Kupffer cells, cells of the endocrine organs, anterior lens capsule and ciliary body, synovial type A cells, mesothelia, adipocytes, and mast cells. Neurons and glia in the central nervous system and spinal cord, cranial and peripheral nerve sheaths, ganglion cells in the sympathetic ganglion, intestinal plexuses, retina, and choroid plexus also regularly exhibited OPN positivity. Testicular germ cells, pancreatic exocrine cells, and follicular dendritic cells reacted with 10A16 only, whereas lutein cells and taste bud cells exhibited O-17 reactivity alone. These minor differences were hypothesized to reflect the state of OPN in the cells; that is, whether OPN was in its whole molecule or fragmented form. In conclusion, we demonstrate that OPN is widely distributed in normal human cells, particularly those comprising the central and peripheral nervous systems. PMID:19784742

Kunii, Yasuto; Niwa, Shin-ichi; Hagiwara, Yoshiaki; Maeda, Masahiro; Seitoh, Tsutomu; Suzuki, Toshimitsu

2009-09-01

124

Problems and process of identity maintenance in the anti-nuclear movement in America: a qualitative analysis  

SciTech Connect

These strategic and tactical problems are examined within two basic areas of concern: (1) external public relations and (2) internal membership identify. This study contributes to the resource-mobilization perspective by theoretically reducing the significant variables of concern to external and internal identity maintenance and by stressing the constant dilemma between the structure of the movement and the actual process by which this structure is carried out. It is based on a social psychological analysis in which the dynamics of social movements is viewed both externally and internally in relation to the movement structure and process. The Sunbelt Alliance anti-nuclear group of Oklahoma is used as the empirical example. The research methodology consists of a series of focused personal interviews. The Sunbelt Alliance anti-nuclear organization experienced a dilemma resulting from the tension between external and internal contingencies. The promotion of cooperative interdependence based on member cohesiveness within the group suffered because of the inability of the organization to maintain consistent agreement concerning external targets. The structure of the group, or its goals and ideology, was not consistently reflected in its process. Disagreement over external priorities eventually reduced internal solidarity, and the organization dissolved.

Tate, D.D.

1982-01-01

125

Combined vaccination and immunostimulatory antibodies provides durable cure of murine melanoma and induces transcriptional changes associated with positive outcome in human melanoma patients  

PubMed Central

We have developed a recombinant adenovirus vaccine encoding dopachrome tautomerase (rHuAd5-hDCT) that produces robust DCT-specific immunity, but only provides modest suppression of murine melanoma. In the current study, an agonist antibody against 4-1BB was shown to enhance rHuAd5-hDCT efficacy and evoke tumor regression, but most tumors ultimately relapsed. The vaccine triggered upregulation of the immune inhibitory PD-1 signaling pathway and PD-1 blockade dramatically enhanced the rHuAd5-hDCT + anti-4-1BB strategy, resulting in complete regression of growing tumors in > 70% of recipients. The impact of the combined anti-4-1BB/anti-PD-1 treatment did not manifest as a dramatic enhancement in either the magnitude or functionality of DCT-specific tumor infiltrating lymphocytes relative to either treatment alone. Rather, a synergistic enhancement in intratumoral cytokine expression was observed, suggesting that the benefit of the combined therapy was a local event within the tumor. Global transcriptional analysis revealed immunological changes within the tumor following the curative vaccination, which extended beyond the T cell compartment. We identified an immune signature of 85 genes associated with clearance of murine melanoma that correlated with improved survival outcome in two independent cohorts of human melanoma patients. Our data reinforce the concept that successful vaccination must overcome local hurdles in the tumor microenvironment that are not manifest within the periphery. Further, tumor rejection following vaccination involves more than simply T cells. Finally, the association of our immune signature with positive survival outcome in human melanoma patients suggests that similar vaccination strategies may be promising for melanoma treatment. PMID:22754760

McGray, A.J. Robert; Bernard, Dannie; Hallett, Robin; Kelly, Ryan; Jha, Mayank; Gregory, Caitlin; Bassett, Jennifer D.; Hassell, John A.; Pare, Guillaume; Wan, Yonghong; Bramson, Jonathan L.

2012-01-01

126

Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on associated lung disease.  

PubMed

Anti-Ku antibodies have been reported in a wide spectrum of autoimmune diseases, sometimes in association with inflammatory myopathies (IM). We studied the clinical, laboratory, and muscle histologic features of all anti-Ku-positive patients detected in our hospital during the last 10 years, as well as their treatment and outcomes. Anti-Ku antibodies were found in 34 patients (0.46% of 20,600 sera positive for antinuclear antibodies), and complete data were available for 30 patients; 86.7% were female, mean age was 49 years (range, 20-73 yr). The most frequent clinical manifestations were arthralgia (77%) and Raynaud phenomenon (53%). Eleven (37%) patients had IM, 8 of them as part of an overlap syndrome defined as IM associated with connective autoimmune disease (5 systemic sclerosis [SSc], 2 Sjögren syndrome (SS), and 1 systemic lupus erythematosus [SLE]). Of 21 patients without IM, 19 had autoimmune diseases (including 6 SLE, 2 SSc, 2 SS, and 2 rheumatoid arthritis), 1 had bronchial neoplasia, and 1 had nephroangiosclerosis. Clinical features of the 9 patients with IM were myalgia (91%), proximal muscle weakness (89%), and dysphagia (36%). All had increased creatine kinase (median, 2210 U/L; range, 194-4073 U/L). Muscle biopsy showed necrosis, inflammation, and positive HLA class I immunostaining. Interstitial lung disease (ILD) was detected on computed tomography (CT) scan in 11 patients (37%) and was significantly more frequent in patients with IM (82% vs. 10.5%, p < 0.001). Fourteen (47%) patients required no immunosuppressive treatment or only a low corticosteroid dose (<15 mg/d, n = 3). A high dose of corticosteroids was more frequently administered in patients with IM (10/11 cases, 80% with associated ILD) than in patients without IM (4/19 cases, 0 with ILD). Complete muscle remission after steroids occurred in 73% of patients with IM. Lung disease was corticoresistant in 6 of 8 (75%) treated cases.Anti-Ku antibodies remain rarely detected, but their presence can be frequently associated with corticosensitive IM and severe, corticoresistant ILD. PMID:22391471

Rigolet, Aude; Musset, Lucile; Dubourg, Odile; Maisonobe, Thierry; Grenier, Philippe; Charuel, Jean-Luc; Behin, Anthony; Herson, Serge; Amoura, Zahir; Benveniste, Olivier

2012-03-01

127

High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis  

PubMed Central

BACKGROUND—High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported.?AIMS—To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH).?PATIENTS—Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested.?METHODS—ANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay.?RESULTS—p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody.?CONCLUSIONS—HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.???Keywords: perinuclear anti-neutrophil cytoplasmic antibodies; chromosomal proteins; high mobility group 1 and 2; autoimmune; hepatitis PMID:10323891

Sobajima, J; Ozaki, S; Uesugi, H; Osakada, F; Inoue, M; Fukuda, Y; Shirakawa, H; Yoshida, M; Rokuhara, A; Imai, H; Kiyosawa, K; Nakao, K

1999-01-01

128

A prospective study of 1038 pregnancies on the predictive value of anti-annexin V antibodies for fetal loss.  

PubMed

Retrospective studies have demonstrated that anti-annexin V (anti-AnxV) antibodies are linked to miscarriage. Their predictive value is, however, unknown. We have carried out a prospective study to evaluate the relationship between anti-AnxV antibodies and the pregnancy outcome. A serum sample was taken from 1038 consecutive healthy women at the beginning of pregnancy. IgG and IgM anti-AnxV antibodies were measured by an ELISA method. The cutoff value was set at 5 units for both IgG and IgM. Out of 1038 women, 116 (11.4%) had a miscarriage by the 22nd week; 10 were lost to follow-up, 10 had an induced abortion, 6 had a preterm delivery, and 896 carried their pregnancy through to term. An adverse outcome of the pregnancy proved to be directly related to the number of previous miscarriages (P = .008) and the age of the woman (P = .002). IgG and IgM anti-AnxV were present in 25% and 27% of the women who miscarried, and in 23% and 28% of those who gave birth (mean antibody concentration IgG, 4.2 vs. 4.4 U/mL; IgM, 3.7 vs. 3.5 U/mL). IgG and IgM anticardiolipin and anti-beta(2)GPI, together with antinuclear, antithyroperoxidase, and antithyroglobulin antibodies, were also measured in the 116 sera of the women with miscarriage and in an equal number of women who gave birth. Their positivity or level proved not to be useful in discriminating between the risk of miscarriage and term delivery. This large-scale prospective study demonstrates that the presence of IgG and IgM anti-AnxV antibodies, when measured in healthy women, does not give a positive predictive lead towards the possibility of a miscarriage, and it is not useful in evaluating the risk of miscarriage at the beginning of pregnancy. PMID:16014551

Bizzaro, N; Antico, A; Musso, M; Platzgummer, S; Camogliano, L; Tozzoli, R; Villalta, D

2005-06-01

129

Expression of Recombinant Antibodies  

PubMed Central

Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications. PMID:23908655

Frenzel, André; Hust, Michael; Schirrmann, Thomas

2013-01-01

130

Antiendothelial cells antibodies in patients with systemic sclerosis in relation to pulmonary hypertension and lung fibrosis.  

PubMed

Although scleroderma is generally considered a fibrosing disease, it is now recognized that the underlying vascular pathology is playing a fundamental role in its pathogenesis. The present study was aimed at testing the prevalence of anti-endothelial cell antibodies (AECA) in systemic scleroderma (SSc) patients with and without pulmonary hypertension (PH) and in relation to the presence of pulmonary fibrosis. Fifty four SSc patients (50 females and 4 male, mean age 55.7 ± 16.3 years) were prospectively screened. All patients underwent transthoracic echocardiography with the estimation of pulmonary artery pressure (PAP) and tricuspid regurgitant peak gradient (TRPG). All patients suspected to have pulmonary hypertension were referred for right heart catheterization. Restrictive lung disease was confirmed by HRCT. A healthy control group included (n = 27; 7 men and 20 women, mean age 49.8 ± 12.1 years). The study of AECA was performed using the indirect immunofluorescence method on commercially available human umbilical vein endothelial cells. The HRCT scans in patients with suspected interstitial lung disease revealed signs of lung fibrosis in 15 (out of the 36 examined patients). TRPG at rest of 31 mmHg was demonstrated in 14 (21%) patients. During cardiac catheterization, arterial PH was found in two patients. Resting venous PH was found in one patient and an excessive post capillary PAP elevation at rest was demonstrated in 11 patients. At the baseline, 14/54 patients (26%) were positive for AECA. In the control group, the frequency of the antibodies was 3/27 (11%). No statistical correlation between antibody titter and the presentation of the disease existed. AECA were highly prevalent in a subgroup of patients suffering from interstitial pulmonary fibrosis. Out of the 15 patients suffering from lung fibrosis, 7 were AECA positive. The presence of AECA correlated very well with antinuclear antibodies (ANA), but was not related to the profile of ANA. Our findings support evidence that endothelial cell damage is involved in SSc, as there was increased prevalence of circulating AECA of the IgG isotype in SSc patients. AECA may also be related to the complications of SSc, like pulmonary fibrosis. PMID:22836630

Lewandowska, K; Ciurzynski, M; Gorska, E; Bienias, P; Irzyk, K; Siwicka, M; Zycinska, K; Pruszczyk, P; Demkow, U

2013-01-01

131

Antibody therapeutics, antibody engineering, and the merits of protein stability.  

PubMed

Antibodies are highly soluble, multidomain proteins that are well suited for biopharmaceutical development; however, engineering antibodies to perform novel activities or to have enhanced clinical utility can have a detrimental effect on their biophysical properties. Various innovative designs, such as single-chain variable fragments (scFvs) and domain antibodies (dAbs), have been utilized to obtain the antigen-binding properties of natural antibodies, while using a minimal amount of the polypeptide sequence of an antibody. These designs can be used for generating diverse antibody libraries to support discovery and optimization and also serve as excellent building blocks for constructing more complex protein therapeutics, such as bispecific antibodies. However, engineered antibody-like proteins, including scFvs, are often unstable and prone to aggregation, compromising both protein production and quality. Research over the past few years has enhanced our understanding of how interdomain interactions within antibodies contribute to protein stability. This knowledge and sustained research to develop methods for modifying antibody fragments to improve stability have begun to have a positive impact on the quality of antibody libraries for discovery purposes and the viability of highly engineered proteins, such as bispecific antibodies, as therapeutics. PMID:18729019

Demarest, Stephen J; Glaser, Scott M

2008-09-01

132

RhD Specific Antibodies Are Not Detectable in HLA-DRB1*1501 Mice Challenged with Human RhD Positive Erythrocytes  

PubMed Central

The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1*1501 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB1*1501 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1*1501 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1*1501 mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1*1501 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1*1501 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed.

Bernardo, Lidice; Denomme, Gregory A.; Shah, Kunjlata; Lazarus, Alan H.

2014-01-01

133

Serum Antibodies from a Subset of Horses Positive for Babesia caballi by Competitive Enzyme-Linked Immunosorbent Assay Demonstrate a Protein Recognition Pattern That Is Not Consistent with Infection  

PubMed Central

Tick-borne pathogens that cause persistent infection are of major concern to the livestock industry because of transmission risk from persistently infected animals and the potential economic losses they pose. The recent reemergence of Theileria equi in the United States prompted a widespread national survey resulting in identification of limited distribution of equine piroplasmosis (EP) in the U.S. horse population. This program identified Babesia caballi-seropositive horses using rhoptry-associated protein 1 (RAP-1)–competitive enzyme-linked immunosorbent assay (cELISA), despite B. caballi being considered nonendemic on the U.S. mainland. The purpose of the present study was to evaluate the suitability of RAP-1–cELISA as a single serological test to determine the infection status of B. caballi in U.S. horses. Immunoblotting indicated that sera from U.S. horses reacted with B. caballi lysate and purified B. caballi RAP-1 protein. Antibody reactivity to B. caballi lysate was exclusively directed against a single ?50-kDa band corresponding to a native B. caballi RAP-1 protein. In contrast, sera from experimentally and naturally infected horses from regions where B. caballi is endemic bound multiple proteins ranging from 30 to 50 kDa. Dilutions of sera from U.S. horses positive by cELISA revealed low levels of antibodies, while sera from horses experimentally infected with B. caballi and from areas where B. caballi is endemic had comparatively high antibody levels. Finally, blood transfer from seropositive U.S. horses into naive horses demonstrated no evidence of B. caballi transmission, confirming that antibody reactivity in cELISA-positive U.S. horses was not consistent with infection. Therefore, we conclude that a combination of cELISA and immunoblotting is required for the accurate serodiagnosis of B. caballi. PMID:24049108

Awinda, Peter O.; Mealey, Robert H.; Williams, Laura B. A.; Conrad, Patricia A.; Packham, Andrea E.; Reif, Kathryn E.; Grause, Juanita F.; Pelzel-McCluskey, Angela M.; Chung, Chungwon; Bastos, Reginaldo G.; Kappmeyer, Lowell S.; Howe, Daniel K.; Ness, SallyAnne L.; Knowles, Donald P.

2013-01-01

134

RhD Specific Antibodies Are Not Detectable in HLA-DRB1(*)1501 Mice Challenged with Human RhD Positive Erythrocytes.  

PubMed

The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1(*)1501 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD(+) RBCs to mice transgenic for the human HLA DRB1(*)1501 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1(*)1501 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1(*)1501 mice immunized with RhD(+) erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1(*)1501 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1(*)1501 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed. PMID:25628657

Bernardo, Lidice; Denomme, Gregory A; Shah, Kunjlata; Lazarus, Alan H

2014-01-01

135

A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members.  

PubMed Central

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE. PMID:3488036

Dudeney, C; Shoenfeld, Y; Rauch, J; Jones, M; Mackworth Young, C; Tavassoli, M; Shall, S; Isenberg, D A

1986-01-01

136

Selective uptake of cylindrical poly(2-oxazoline) brush-antiDEC205 antibody-OVA antigen conjugates into DEC-positive dendritic cells and subsequent T-cell activation.  

PubMed

To achieve specific cell targeting by various receptors for oligosaccharides or antibodies, a carrier must not be taken up by any of the very many different cells and needs functional groups prone to clean conjugation chemistry to derive well-defined structures with a high biological specificity. A polymeric nanocarrier is presented that consists of a cylindrical brush polymer with poly-2-oxazoline side chains carrying an azide functional group on each of the many side chain ends. After click conjugation of dye and an anti-DEC205 antibody to the periphery of the cylindrical brush polymer, antibody-mediated specific binding and uptake into DEC205(+) -positive mouse bone marrow-derived dendritic cells (BMDC) was observed, whereas binding and uptake by DEC205(-) negative BMDC and non-DC was essentially absent. Additional conjugation of an antigen peptide yielded a multifunctional polymer structure with a much stronger antigen-specific T-cell stimulatory capacity of pretreated BMDC than application of antigen or polymer-antigen conjugate. PMID:25111768

Bühler, Jasmin; Gietzen, Sabine; Reuter, Anika; Kappel, Cinja; Fischer, Karl; Decker, Sandra; Schäffel, David; Koynov, Kaloian; Bros, Matthias; Tubbe, Ingrid; Grabbe, Stephan; Schmidt, Manfred

2014-09-22

137

A case of catastrophic antiphospholipid antibody syndrome complicated with systemic lupus erythematosus, double positive for anti-cardiolipin/?? glycoprotein I and anti-phosphatidylserine/prothrombin autoantibodies.  

PubMed

A 16-year-old male with severe thrombocytopenia and progressive multiple organ infarctions was diagnosed as having catastrophic antiphospholipid syndrome (CAPS) complicated with systemic lupus erythematosus, and was successfully treated with combination of anticoagulants, corticosteroids, plasma exchange, and intravenous cyclophosphamide. Antibodies to phosphatidylserine/prothrombin (PS/PT) complex and cardiolipin (CL)/?(2)-glycoprotein I (?(2)GPI) were simultaneously detected, indicating that the different pathways of both PS/PT and CL/?(2)GPI might be associated with the radical manifestation of CAPS. PMID:22124547

Hirakawa, Eri; Saito, Kazuyoshi; Hirata, Shintaro; Atsumi, Tatsuya; Koike, Takao; Tanaka, Yoshiya

2012-09-01

138

Bispecific anti-CD3 x anti-HER2 antibody mediates T cell cytolytic activity to HER2-positive colorectal cancer in vitro and in vivo.  

PubMed

Targeting HER2 overexpressed breast cancer cells with anti?HER2 monoclonal antibodies inhibits tumor growth. Here we investigated whether HER2 can serve as a target for T cell-mediated immunotherapy of human colorectal carcinoma. Specific cytolytic activity of activated T cells (ATCs) armed with anti?CD3 x anti?HER2 bispecific antibody (HER2Bi-Ab) against HER2+ tumor cells was evaluated by bioluminescent signal generated by luciferase reporter on tumor cells in vitro and in vivo. In contrast to unarmed ATCs, increased cytotoxic activity of HER2Bi-armed ATCs against HER2+ tumor cells was observed. Moreover, HER2Bi-armed ATCs expressed higher level of activation marker CD69 and secreted significantly higher levels of IFN-? than the unarmed ATC counterpart. In addition, compared with anti?HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATCs showed significant suppression against colorectal carcinoma cells. In colorectal tumor cell xenograft mice, infusion of HER2Bi-armed ATCs successfully inhibited the growth of Colo205-luc cells. The HER2Bi-armed ATCs with anti-tumor effects may provide a promising immunotherapy for colorectal carcinoma in the future. PMID:25242665

Han, Huamin; Ma, Juan; Zhang, Keming; Li, Wei; Liu, Changzhen; Zhang, Yu; Zhang, Ganlin; Ma, Pan; Wang, Lei; Zhang, Ge; Tao, Hua; Gao, Bin

2014-12-01

139

Serum interferon-? is a useful biomarker in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis.  

PubMed

Abstract Objective. We have tried to clarify the clinical importance of the measurement of serum type-I interferon (IFN) in patients with anti-melanoma differentiation-associated gene 5 Ab (MDA5 Ab)-positive dermatomyositis (DM). Methods. We studied 30 patients with DM: 10 were anti-MDA5 Ab-positive and 20 were anti-MDA5 Ab-negative. At each patient's initial visit, serum IFN-?, IFN-?, interleukin 18 (IL-18), ferritin, and the titer of anti-MDA5 Ab were measured using enzyme-linked immunosorbent assays (ELISAs). The associations between the IFNs and with the other variables were examined. Results. Rapidly progressive interstitial lung disease (RPILD) was confirmed in 10 patients, most of whom were complicated in the anti-MDA5 Ab-positive DM patients. The presence of clinically amyopathic dermatomyositis (CADM) as well as the serum concentrations of IFN-? and ferritin was significantly higher in the anti-MDA5 Ab-positive DM patients. Serum concentration of IL-18 did not differ between anti-MDA5 Ab-positive and anti-MDA5 Ab-negative groups; however, a positive correlation was found between IFN-? and IL-18 in the anti-MDA5 Ab-positive DM patients (r = 0.8139, p = 0.0146). Conclusion. Serum IFN-? can be used as a useful biomarker in patients with anti-MDA5 Ab-positive DM, which may reflect the presence of RPILD. PMID:24716595

Horai, Yoshiro; Koga, Tomohiro; Fujikawa, Keita; Takatani, Ayuko; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Kawashiri, Shin-Ya; Iwamoto, Naoki; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Ida, Hiroaki; Kakugawa, Tomoyuki; Sakamoto, Noriho; Ishimatsu, Yuji; Mukae, Hiroshi; Hamaguchi, Yasuhito; Fujimoto, Manabu; Kuwana, Masataka; Origuchi, Tomoki; Kohno, Shigeru; Kawakami, Atsushi

2015-01-01

140

Rh Antibodies Detectable only by Enzyme Technique  

PubMed Central

The titration of Rh antibodies at intervals during pregnancy by various methods has led to evidence for the existence of an Rh antibody or antibodies detectable by an enzyme (papain) method but not by anti-human-globulin. Adsorption experiments show that this antibody is less readily absorbed by red cells than the other Rh antibodies unless the cells are pretreated with enzyme. This fact may possibly account for the finding of a negative or weakly positive anti-human-globulin test associated with moderate or high titres by enzyme techniques. The relationship of this antibody to the general immunization process in pregnant women is discussed. PMID:13886834

Dodd, Barbara E.; Eeles, Doreen A.

1961-01-01

141

Antibody Dendrimers  

NASA Astrophysics Data System (ADS)

Supramolecular formations of antibodies by their specific molecular recognition to antigens are investigated. Linear and network supramolecular architectures have been constructed by using immunoglobulin G (IgG) and divalent or trivalent antigens, respectively. An amplification method of the detection signals for the target molecule in the biosensors based on the surface plasmon resonance (SPR) has been devised using the signal enhancement in the supramolecular assembly of the antibody with multivalent antigens. Novel dendritic supramolecular complexes are designed and prepared by using immunoglobulin M (IgM) or protein A/G as a core and IgGs as branches. One of the "antibody dendrimers" is composed of proteins with a molecular weight of about 2 million and constructed by non-covalent bonds. The dendrimer can bind antigens strongly with high specificity. The biosensor technique based on SPR shows that the antibody dendrimer has the advantage of amplification of detection signals for antigens.

Yamaguchi, Hiroyasu; Harada, Akira

142

Antibody dendrimers.  

PubMed

Supramolecular formations of antibodies by their specific molecular recognition to antigens are investigated. Linear and network supramolecular architectures have been constructed by using immunoglobulin G (IgG) and divalent or trivalent antigens, respectively. An amplification method of the detection signals for the target molecule in the biosensors based on the surface plasmon resonance (SPR) has been devised using the signal enhancement in the supramolecular assembly of the antibody with multivalent antigens. Novel dendritic supramolecular complexes are designed and prepared by using immunoglobulin M (IgM) or protein A/G as a core and IgGs as branches. One of the "antibody dendrimers" is composed of proteins with a molecular weight of about 2 million and constructed by non-covalent bonds. The dendrimer can bind antigens strongly with high specificity. The biosensor technique based on SPR shows that the antibody dendrimer has the advantage of amplification of detection signals for antigens. PMID:21132488

Yamaguchi, Hiroyasu; Harada, Akira

2003-01-01

143

Anti-HIV Activity in Cervical-Vaginal Secretions from HIV- Positive and-Negative Women Correlate with Innate Antimicrobial Levels and IgG Antibodies  

E-print Network

Background: We investigated the impact of antimicrobials in cervicovaginal lavage (CVL) from HIV(+) and HIV(2) women on target cell infection with HIV. Since female reproductive tract (FRT) secretions contain a spectrum of antimicrobials, we hypothesized that CVL from healthy HIV(+) and (2) women inhibit HIV infection. Methodology/Principal Findings: CVL from 32 HIV(+) healthy women with high CD4 counts and 15 healthy HIV(2) women were collected by gently washing the cervicovaginal area with 10 ml of sterile normal saline. Following centrifugation, anti-HIV activity in CVL was determined by incubating CVL with HIV prior to addition to TZM-bl cells. Antimicrobials and antigp160 HIV IgG antibodies were measured by ELISA. When CXCR4 and CCR5 tropic HIV-1 were incubated with CVL from HIV(+) women prior to addition to TZM-bl cells, anti-HIV activity in CVL ranged from none to 100 % inhibition depending on the viral strains used. CVL from HIV(2) controls showed comparable anti-HIV activity. Analysis of CH077.c (clone of an R5tropic, mucosally-transmitted founder virus) viral inhibition by CVL was comparable to laboratory strains. Measurement of

Mimi Ghosh; John V. Fahey; Zheng Shen; Timothy Lahey; Susan Cu-uvin; Zhijin Wu; Peter F. Wright; Christina Ochsenbauer; Charles R. Wira

144

Dynamic adhesion of CD8-positive cells to antibody-coated surfaces: the initial step is independent of microfilaments and intracellular domains of cell-binding molecules  

PubMed Central

Cell adhesion is a multistep, metabolically active process usually requiring several minutes or even hours to complete. This results in the formation of strong bonds that cannot be ruptured by mechanical forces encountered by living cells in their natural environment. However, the first seconds after contact formation are much more sensitive to external conditions and may be the critical step of adhesion. This step is very difficult to monitor without disturbing the observed system. We addressed this problem by studying the interaction between anti-CD8-coated or control surfaces and murine lymphoid cell lines bearing wild-type CD8 molecules, or genetically engineered molecules bearing extracellular CD8 domains and transmembranar and intracytoplasmic domains of class I histocompatibility molecules, or with extensive deletion of intracytoplasmic domains. We used a new method that consisted of monitoring the motion of cells driven along adhesive surfaces by a hydrodynamic force weaker than the reported strength of single ligand-receptor bonds, but sufficient to make free cells move with an easily detectable velocity of several micrometers per second. Cells exhibited short-term (< or = 0.5 s) adhesions to the surface with a frequency of about one event per 30-s period of contact. These events did not require specific antigen-antibody bonds. However, when anti-CD8 were present, strong adhesion was achieved within < 1 s, since most arrests were longer than a standard observation period of 1 min. This bond strengthening was not affected by cytochalasin, and it did not require intact intracellular domains on binding molecules. It is concluded that the initial step in strong adhesion may be viewed as a passive, diffusion-driven formation of a new specific bonds. PMID:8188755

1994-01-01

145

Dynamic adhesion of CD8-positive cells to antibody-coated surfaces: the initial step is independent of microfilaments and intracellular domains of cell-binding molecules.  

PubMed

Cell adhesion is a multistep, metabolically active process usually requiring several minutes or even hours to complete. This results in the formation of strong bonds that cannot be ruptured by mechanical forces encountered by living cells in their natural environment. However, the first seconds after contact formation are much more sensitive to external conditions and may be the critical step of adhesion. This step is very difficult to monitor without disturbing the observed system. We addressed this problem by studying the interaction between anti-CD8-coated or control surfaces and murine lymphoid cell lines bearing wild-type CD8 molecules, or genetically engineered molecules bearing extracellular CD8 domains and transmembranar and intracytoplasmic domains of class I histocompatibility molecules, or with extensive deletion of intracytoplasmic domains. We used a new method that consisted of monitoring the motion of cells driven along adhesive surfaces by a hydrodynamic force weaker than the reported strength of single ligand-receptor bonds, but sufficient to make free cells move with an easily detectable velocity of several micrometers per second. Cells exhibited short-term (< or = 0.5 s) adhesions to the surface with a frequency of about one event per 30-s period of contact. These events did not require specific antigen-antibody bonds. However, when anti-CD8 were present, strong adhesion was achieved within < 1 s, since most arrests were longer than a standard observation period of 1 min. This bond strengthening was not affected by cytochalasin, and it did not require intact intracellular domains on binding molecules. It is concluded that the initial step in strong adhesion may be viewed as a passive, diffusion-driven formation of a new specific bonds. PMID:8188755

Pierres, A; Tissot, O; Malissen, B; Bongrand, P

1994-05-01

146

DRESS syndrome with fatal results induced by sodium valproate in a patient with brucellosis and a positive cytoplasmic antineutrophilic cytoplasmic antibody test result.  

PubMed

DRESS syndrome is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. DRESS syndrome related to valproic acid use is very rarely observed. We present a case of DRESS syndrome induced by sodium valproate, which developed and progressed fatally in a brucellosis patient with a positive c-ANCA test. A 19-year-old female patient presented with fever, cough, jaundice, and rash all over her body. Brucella Coombs test was positive at 1:1280 titers, and the Rose Bengal test was also positive. The involuntary movements were thought to be due to chorea, and the patient was started on sodium valproate 500 mg 2 1, as well as streptomycin 1 g flk 1 1 and tetradox capsules 2 1 for the brucellosis and was discharged. DRESS syndrome was suspected in the patient, and she was taken off sodium valproate and tetradox; N-acetylcysteine, ceftriaxon, prednizolone, and support treatment were started. When sodium valproate is used on its own, it carries no risk of inducing DRESS syndrome. However, in the case presented, another co-morbidity such as brucellosis and c-ANCA positivity was present. We believe that the presence of further co morbidity not yet reported in literature is important from the perspective of the risk of valproate-induced DRESS syndrome. Therefore, if sodium valproate treatment is to be started in patients, especially those with co morbidity, they must be closely monitored with clinical and laboratory observations. At the slightest suspicion of DRESS syndrome, all medication should be ceased immediately and the patient should be placed under continuous observation. PMID:20354855

Albayrak, Fatih; Cerrah, Serkan; Albayrak, Ayse; Dursun, Hakan; Yildirim, Rahsan; Uyanik, Abdullah

2012-07-01

147

[Efficacy of combination therapy with pegylated-interferon alfa-2a plus ribavirin in autoantibody-positive chronic hepatitis C patients].  

PubMed

To evaluate the therapeutic efficacy of antiviral combination therapy with pegylated-interferon alpha-2a plus ribavirin (RBV) in patients with autoantibody-positive chronic hepatitis C (CHC) and to investigate the impact of the presence of autoantibodies on the treatment outcome. Eighty-six consecutive CHC patients who underwent a 48-week treatment regimen composed of Peg-IFNa-2a (135 or 180 mug/wk) plus weight-based RBV ( less than or equal to 65 kg, 800 mg/d; 65 to 75 kg, 1000 mg/d; more than or equal to75 kg, 1200 mg/d ). Prior to treatment (baseline) and at end of treatment (EOT; week 48), levels of antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), anti liver/kidney microsomal antibody type 1 (LKM1), anti-La (SSB), and anti liver cytosolic-1 (LC-1) were detected by indirect immunofluorescence. At baseline, during treatment (weeks 4, 12, 24, and 36), EOT, and 24 weeks after EOT, levels of HCV RNA were assessed by real-time quantitative PCR. Rapid virological response (RVR) was defined as HCV RNA less than 10(3) copy/ml at week 4. Sustained virologic response (SVR) was defined as HCV RNA load below the lower limit of detection at 24 weeks after EOT. Correlation between autoantibodies and treatment-induced reduced HCV RNA load was assessed by univariate analysis of variance or chi-squared tests. Autoantibodies were detected in 24 patients, which included 14 ANA-positive patients, five SMA-positive patients, three LKM1-positive patients, one patient with double-positivity for ANA and SSB, and one patient with double-positivity for ANA and LC-1. The autoantibody-positive patients and autoantibody-negative patients showed similar rates of RVR (70.8% vs. 72.5%, P more than 0.05) and SVR (81.4% vs. 82.2%, P more than 0.05). Antiviral therapy with Peg-IFNa-2a RBV can effectively reduce the HCV RNA load in autoantibody-positive CHC patients; however, the presence of autoantibodies may not be an independent predictor of therapy outcome. PMID:24025134

Li, Ya-xin; Yang, Yan-jia; Yang, Mei; Chen, Li-yu; Lu, Jia-jie; Ma, Yuan-ji; Liu, Kai; Lei, Xue-zhong; Tang, Hong

2013-05-01

148

Recently Added Antibodies  

Cancer.gov

Reagents Data Portal AntibodiesNCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit. Print

149

Auto-Antibodies and Their Association with Clinical Findings in Women Diagnosed with Microscopic Colitis  

PubMed Central

Background Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. Methods and Findings Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59–67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. Conclusions Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC. PMID:23776613

Ohlsson, Bodil

2013-01-01

150

Antiphospholipid antibodies  

Microsoft Academic Search

Conclusion  Confirmatory evidence that aPL (the LA or aCL) are associated with an increased risk for arterial and venous thrombosis, recurrent\\u000a spontaneous abortions, and fetal loss has led to increased laboratory requests for identification of these antibodies. Criteria\\u000a for the definition of the APS is now well established. At present both the pathogenesis and the optimal management of the\\u000a syndrome are

Munther A. Khamashta; Graham R. V. Hughes

1994-01-01

151

Postnatal decline of maternally acquired rubella antibodies  

PubMed Central

The postnatal decline of maternally acquired rubella antibody was studied in a large group of infants. A high degree of variability was found in the rate of antibody decline (half-life). Ninety-two babies had rubella antibody half-lives lying between 14 and 70 days and three had values considerably higher. There was no significant difference between the rubella antibody half-lives of the sexes. The antibody titre at birth was weakly correlated with both birth weight and gestational age. There was a highly significant positive correlation between the baby's antibody titre at birth and that of its mother. There was a positive relationship between the half-life and the persistence of rubella antibody. Some babies had no detectable antibody by 2 months whereas others still possessed antibody at 9 months. It was found that the relationship between the half-life and the rubella antibody titre at or near birth could be described by a rectangular hyperbola. PMID:5272346

Cloonan, M. J.; Hawkes, R. A.; Stevens, L. H.

1970-01-01

152

In ACPA-positive RA patients, antibodies to EBNA35-58Cit, a citrullinated peptide from the Epstein-Barr nuclear antigen-1, strongly cross-react with the peptide ?60-74Cit which bears the immunodominant epitope of citrullinated fibrin.  

PubMed

Although several infectious agents and particularly Epstein-Barr virus (EBV) have been suspected to be involved in aetiology of rheumatoid arthritis (RA), their role still remains elusive. Almost 80 % of RA sera contain antibodies to citrullinated proteins/peptides. Among them, the autoantibodies to citrullinated human fibrinogen (AhFibA) are composed of two non-cross-reactive subsets directed to immunodominant epitopes borne by the ?36-50Cit and ?60-74Cit fibrin peptides. RA sera also contain antibodies towards the citrullinated EBNA35-58Cit peptide derived from the EBNA-1 protein of EBV. Here, using a large cohort of RA patients and controls, we showed that for a diagnostic specificity of 98.5 %, 47 % of the AhFibA-positive patients were anti-EBNA35-58Cit-positive and that almost all (98.5 %) the anti-EBNA35-58Cit-positive were AhFibA-positive, whereas 86 % were anti-?60-74Cit-positive and only 43 % anti-?36-50Cit-positive. AhFibA, anti-EBNA35-58Cit- and anti-?60-74Cit-antibody titres were significantly correlated. Competition assays showed that anti-EBNA35-58Cit antibodies are highly cross-reactive with the ?60-74Cit peptide. The demonstration that a citrullinated peptide derived from the EBNA-1 protein of EBV presents a molecular mimicry with human citrullinated fibrin constitutes an additional argument for a possible role of EBV in RA aetiopathogeny. PMID:25407647

Cornillet, M; Verrouil, E; Cantagrel, A; Serre, G; Nogueira, L

2014-11-19

153

Reagents Data Portal Antibodies  

Cancer.gov

NCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit.

154

Ideology, interest-group formation, and protest: the case of the anti-nuclear power movement, the Clamshell Alliance, and the New Left  

SciTech Connect

The thesis analyzes the development of the Clamshell Alliance, the first and most successful anti-nuclear power protest group. The key question the dissertation asks is how did this organization stage such popular and well-attended protests during a period when leftist political activity seemed to have died out, and little mass protest was taking place. The thesis also explores why the Clamshell Alliance disintegrated at the same time as the anti-nuclear power movement's cause was gaining public acceptance in the wake of the Three Mile Island power-plant accident. The thesis finds that the principal resources the Clamshell drew upon to solve the problems of organizational formation were the activists, organizations, and ideology of the surviving New Left. The dissertation studies the struggles of the Clamshell Alliance as an example of the recurrent problems of leftist political activism in the U.S. It is concluded that only under special conditions can protest outside of regular political channels be both popular and effective. It is also proved that a larger organizational and ideological legacy of the sixties remains than is generally recongnized. Leftist beliefs continued to have adherents even after the protests stopped. Further, many individuals who came to political maturity after the sixties also were found to hold leftist beliefs. However, the political potential of this group can only be realized when an organization temporarily overcomes the barriers to mass leftist political action by developing an issue and a set of tactics that can appeal to leftists and nonleftists alike. Between such special acts of innovation the Left remains a political undercurrent outside of mainstream politics and without a means of effective influence because of its unwillingness to engage in conventional politics.

Cohen, E.M.

1981-01-01

155

The F1000Research Antibody Validation Article Collection.  

PubMed

Well validated antibodies are crucial to progress in a wide range of life science disciplines, but validating an antibody is a complex and ongoing process. Antibody validation is often carried out as preliminary work to a larger study so the validation data may go unpublished and needless duplication of efforts can occur. This collection of articles in F1000Research provides a home for papers describing antibody validation studies. Our goal is to encourage publishing of all studies, both positive and negative, which increase understanding of how antibodies perform. These could range from large studies with thousands of antibodies to small single figure studies which validate an individual antibody for a specific purpose. Opinion or Correspondence articles considering any aspect of antibody validation are also welcome. Here, we provide an introduction to the collection which we hope will grow and become a valuable resource for the many thousands of researchers who use antibodies. PMID:25580229

Helsby, Matthew A; Leung, Mei Yee; Chalmers, Andrew D

2014-01-01

156

The F1000Research Antibody Validation Article Collection  

PubMed Central

Well validated antibodies are crucial to progress in a wide range of life science disciplines, but validating an antibody is a complex and ongoing process. Antibody validation is often carried out as preliminary work to a larger study so the validation data may go unpublished and needless duplication of efforts can occur. This collection of articles in F1000Research provides a home for papers describing antibody validation studies. Our goal is to encourage publishing of all studies, both positive and negative, which increase understanding of how antibodies perform. These could range from large studies with thousands of antibodies to small single figure studies which validate an individual antibody for a specific purpose. Opinion or Correspondence articles considering any aspect of antibody validation are also welcome. Here, we provide an introduction to the collection which we hope will grow and become a valuable resource for the many thousands of researchers who use antibodies. PMID:25580229

Helsby, Matthew A.; Leung, Mei Yee; Chalmers, Andrew D.

2014-01-01

157

Renewable, recombinant antibodies to histone post-translational modifications  

PubMed Central

Variability in the quality of antibodies to histone post-translational modifications (PTMs) presents widely recognized hindrance in epigenetics research. Here, by using antibody engineering technologies we produced recombinant antibodies directed to the trimethylated lysine residues of histone H3 with high specificity and affinity and no lot-to-lot variation. These recombinant antibodies performed well in common epigenetics applications, and their high specificity enabled us to identify positive and negative correlations among histone PTMs. PMID:23955773

Hattori, Takamitsu; Taft, Joseph M.; Swist, Kalina M.; Luo, Hao; Witt, Heather; Slattery, Matthew; Koide, Akiko; Ruthenburg, Alexander J.; Krajewski, Krzysztof; Strahl, Brian D.; White, Kevin P.; Farnham, Peggy J.; Zhao, Yingming; Koide, Shohei

2013-01-01

158

Acid treatment of lymphocytes selectively decreases the expression of HLA class I antigens: a method to confirm that a positive clinical crossmatch test was due to class I antibodies.  

PubMed

A rapid and reliable method for eliminating HLA class I antigens from the surface of lymphocytes without damaging the cells is described. Lymphocytes were exposed to an acid solution (pH 3.0) which selectively destroys the antigenicity of HLA class I antigens. Alloantisera containing multispecific HLA class I antibodies reacted with phosphate-buffered saline (PBS)-treated, but not with acid-treated, lymphocytes. Specificity controls included: antibodies against HLA class II antigens and CD3, CD4, CD8; markers expressed on T cells and CD19, CD23; markers expressed on B cells. No change in lymphocyte reactivity to any of these surface antigens or to autoantibodies was observed. The viability of acid-treated lymphocytes was regularly around 90%. We propose that acid-treated lymphocytes are suitable targets for determination of the sole presence of class I antibodies in crossmatch sera of patients awaiting organ transplants. PMID:8843594

Sumitran-Karuppan, S; Möller, E

1996-06-01

159

Coeliac Disease-Associated Antibodies in Psoriasis  

PubMed Central

Background The possible relationship between psoriasis and coeliac disease (CD) has been attributed to the common pathogenic mechanisms of the two diseases and the presence of antigliadin antibodies in patients has been reported to increase the incidence of CD. Objective The aim of this report was to study CD-associated antibodies serum antigliadin antibody immunoglobulin (Ig)A, IgG, anti-endomysial antibody IgA and anti-transglutaminase antibody IgA and to demonstrate whether there is an increase in the frequency of those markers of CD in patients with psoriasis. Methods Serum antigliadin antibody IgG and IgA, antiendomysial antibody IgA and anti-transglutaminase antibody IgA were studied in 37 (19 males) patients with psoriasis and 50 (23 males) healthy controls. Upper gastrointestinal endoscopy and duodenal biopsies were performed in patients with at least one positive marker. Results Antigliadin IgA was statistically higher in the psoriasis group than in the controls (p<0.05). Serological markers were found positive in 6 patients with psoriasis and 1 person from the control group. Upper gastrointestinal endoscopy was performed in all these persons, with biopsies collected from the duodenum. The diagnosis of CD was reported in only one patient with psoriasis following the pathological examination of the biopsies. Whereas one person of the control group was found to be positive for antigliadin antibody IgA, pathological examination of the duodenal biopsies obtain from this patient were found to be normal. Conclusion Antigliadin IgA prominently increases in patients diagnosed with psoriasis. Patients with psoriasis should be investigated for latent CD and should be followed up. PMID:24003271

Akbulut, Sabiye; Gür, Günes; Topal, Firdevs; Topal, Fatih Esad; Alli, Nuran; Saritas, Ülkü

2013-01-01

160

Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis.  

PubMed Central

Ulcerative colitis (UC) is an inflammatory bowel disease of unknown aetiology. In this study, serum samples from 80 patients with UC were studied for the presence of various autoantibodies and soluble interleukin-2 receptor molecules (sIL-2Rs) in an attempt to determine the degree of activation of the immune system in this disease process. Autoantibodies detected included rheumatoid factors (in 5% of patients), antinuclear antibodies (in 51.3%), anti-Ro(SSA) (in 1.3%), anticardiolipin antibodies (IgG and/or IgM classes in 26.3%), anti-double stranded DNA (IgG or IgM classes in 45%), and antineutrophil cytoplasmic antibodies (ANCAs, in 30%). The ANCAs had a perinuclear pattern (p-ANCA) in 95.8%, without anti-myeloperoxidase activity, at least in an enzyme linked immunosorbent assay (ELISA) system. Raised concentrations of sIL-2R were found in 32.5% of patients (26/80, 18 with active and eight with inactive UC). The mean (SD) sIL-2R concentrations were significantly higher in patients with active UC (595 (219) u/ml v 406 (162) u/ml, p = 0.0001) and in patients with ANCAs (584 (177) u/ml in ANCA positive v 447 (212) u/ml in ANCA negative patients, p < 0.01). The sIL-2R concentrations were correlated with increased serum concentrations of C3c (r = 0.23, p < 0.05) or C4 (r = 0.4, p < 0.001) components of the complement system and erythrocyte sedimentation rate (ESR, r = 0.44, p = 0.0001). Platelets, ESR, and C3c were not associated with disease activity (p = 0.06, 0.33 and 0.86) whereas mean (SD) serum concentrations of C4 were higher in active disease (37.4 (11.9) mg/dl v 32.3 (10.3) mg/dl, p < 0.05). The sIL-2Rs had 53% sensitivity and 82.6% specificity for disease activity whereas platelet counts had 53% sensitivity and 58.7% specificity. To conclude, UC is accompanied by an autoimmune response that results in the production of several autoantibodies and cellular immune activation, as shown by the high sIL-2R concentration, is also present. The identification of the target antigen(s) of p-ANCA would possibly act as an indicator of disease activity if this distinct subset of ANCAs can be attributed to the pathogenesis of UC. The sIL-2R concentrations seem to be a useful laboratory marker for assessing activity of the disease. PMID:8504967

Dalekos, G N; Manoussakis, M N; Goussia, A C; Tsianos, E V; Moutsopoulos, H M

1993-01-01

161

Other Autonomic Neuropathies Associated with Ganglionic Antibody  

PubMed Central

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders. PMID:19058765

Sandroni, Paola; Low, Phillip A.

2009-01-01

162

Other autonomic neuropathies associated with ganglionic antibody.  

PubMed

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer. This review describes the autonomic neuropathies most frequently encountered in clinical practice in which an autoimmune etiology is suspected. They include a chronic form (pure autonomic failure) and limited autonomic neuropathies with predominant involvement of one neurotransmitter type (i.e., cholinergic vs. adrenergic) or one system (such as the gastrointestinal system) or a distal small fiber dysfunction. In each of these conditions, occasional positivity to the G-AchR antibody has been found, but the pathogenetic significance of such finding is still uncertain. Other antigens and antibodies yet to be identified are more likely to be responsible in these disorders. PMID:19058765

Sandroni, Paola; Low, Phillip A

2009-03-12

163

Platelet associated antibodies  

MedlinePLUS

... need this test when you have a low platelet count (thrombocytopenia). It is used to detect antibodies against ... platelets and destroy them. This causes a low platelet count, which can lead to excessive bleeding. Antiplatelet antibodies ...

164

GE Healthcare Antibody Purification  

E-print Network

GE Healthcare Antibody Purification Handbook GE Healthcare imagination at work agination at work from GE Healthcare #12;Antibody Purification Handbook #12; Handbook 18-1037-46 AD Contents Introduction

Lebendiker, Mario

165

Other autonomic neuropathies associated with ganglionic antibody  

Microsoft Academic Search

The acetylcholine receptor ganglionic (G-AchR) antibody is a very specific serologic test for autoimmune autonomic ganglionopathy. The spectrum of autoimmune (or presumed to be autoimmune) autonomic disorders, however, is quite broad and positivity to this antibody has been reported in a variety of other conditions, albeit infrequent and with low titer.This review describes the autonomic neuropathies most frequently encountered in

Paola Sandroni; Phillip A. Low

2009-01-01

166

Antibody profiling sensitivity through increased reporter antibody layering  

DOEpatents

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Apel, William A; Thompson, Vicki S

2013-02-26

167

Antibodies, viruses and vaccines  

Microsoft Academic Search

Neutralizing antibodies are crucial for vaccine-mediated protection against viral diseases. They probably act, in most cases, by blunting the infection, which is then resolved by cellular immunity. The protective effects of neutralizing antibodies can be achieved not only by neutralization of free virus particles, but also by several activities directed against infected cells. In certain instances, non-neutralizing antibodies contribute to

Dennis R. Burton

2002-01-01

168

Peptide antibodies and their use in detecting oncogene products  

SciTech Connect

A polyclonal antibody preparation is described. It binds selectively to a characteristic marker epitope encompassing amino acid position 12 of an activated form of p21 protein, wherein the polyclonal antibody preparation is specific for a particular polyclonal antibody amino acid at position 12 and does not bind the p21 protein encoded by the corresponding proto-oncogene. A method for detecting an activated form of p21 protein is also described. It is encoded by an oncogene in a cellular sample of a patient which protein has a characteristic marker epitope encompassing amino acid position 12 which is not present in the p21 protein encoded by the corresponding proto-oncogene and which is not exposed in the undenatured protein. The method comprises: (a) treating the sample with a protein denaturing agent that causes the epitope to be exposed and does not substantially inhibit binding of an antibody to the epitope of the protein, (b) incubating the sample with the antibody under conditions that permit the binding of the antibody preparation to the epitope, (c) incubating the sample with a labeled antibody which binds specifically to the antibody employed in step (b), (d) washing the incubated sample to remove unbound labeled antibody, and (e) detecting the presence of labelled immune complexes of the epitope with the antibodies employed in steps (b) and (c).

Wong, G.L.; Arnheim, N.; McCormick, F.P.; Wong, G.L.; Clark, R.; Arnheim, N.; Nitecki, D.E.

1989-01-17

169

[VGKC-complex antibodies].  

PubMed

Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease). PMID:23568988

Watanabe, Osamu

2013-04-01

170

Method for altering antibody light chain interactions  

DOEpatents

A method for recombinant antibody subunit dimerization including modifying at least one codon of a nucleic acid sequence to replace an amino acid occurring naturally in the antibody with a charged amino acid at a position in the interface segment of the light polypeptide variable region, the charged amino acid having a first polarity; and modifying at least one codon of the nucleic acid sequence to replace an amino acid occurring naturally in the antibody with a charged amino acid at a position in an interface segment of the heavy polypeptide variable region corresponding to a position in the light polypeptide variable region, the charged amino acid having a second polarity opposite the first polarity. Nucleic acid sequences which code for novel light chain proteins, the latter of which are used in conjunction with the inventive method, are also provided.

Stevens, Fred J. (Naperville, IL); Stevens, Priscilla Wilkins (Evanston, IL); Raffen, Rosemarie (Elmhurst, IL); Schiffer, Marianne (Downers Grove, IL)

2002-01-01

171

Passive West Nile virus antibody transfer from maternal Eastern screech-owls (Megascops asio) to progeny.  

PubMed

Transovarial antibody transfer in owls has not been demonstrated for West Nile virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal antibody transfer, as well as titers and duration of maternal antibodies. Twenty-four owlets aged 1 to 27 days old circulated detectable antibodies with neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating that WNV antibodies are passively transferred transovarially is important for accurate interpretation of serologic data from young birds. PMID:17039850

Hahn, D C; Nemeth, Nicole M; Edwards, Eric; Bright, Patricia R; Komar, Nicholas

2006-09-01

172

Passive West Nile virus antibody transfer from maternal Eastern Screech-Owls (Megascops asio) to progeny  

USGS Publications Warehouse

Transovarial antibody transfer in owls has not been demonstrated for West Nile virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal antibody transfer, as well as titers and duration of maternal antibodies. Twenty-four owlets aged 1 to 27 days old circulated detectable antibodies with neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating that WNV antibodies are passively transferred transovarially is important for accurate interpretation of serologic data from young birds.

Hahn, D.C.; Nemeth, N.M.; Edwards, E.; Bright, P.R.; Komar, N.

2006-01-01

173

Biobarcodes: Antibodies and Nanosensors  

NSDL National Science Digital Library

In this activity/demo, learners investigate biobarcodes, a nanomedical technology that allows for massively parallel testing that can assist with disease diagnosis. Learners define antibodies and learn how each antibody binds to a unique protein. Learners also discover how biobarcoding uses nanoparticles, antibodies, DNA and magnetism to detect diseases earlier than we could detect before. Learners assemble a jigsaw puzzle that models how biobarcodes work.

Nanoscale Informal Science Education Network

2014-06-04

174

RSV antibody test  

MedlinePLUS

Respiratory syncytial virus antibody test; RSV serology ... Breese HC. Respiratory syncytial virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandel, Douglas, and Bennett's Principles and Practice of ...

175

Natural Antibodies Against Sialoglycans.  

PubMed

Natural antibodies, part of the innate immunity system, are produced at strictly regulated levels in normal sera without immunization and thus are part of the innate immune system. The best studied natural antibodies are those directed against blood group antigens A and B and xeno-antigens including glycolylneuraminic acid containing Hanganutziu-Deicher (HD) glycolipid. Abnormal levels of anti-glycan antibodies were found in a number of pathologies. In many cases pathological antibodies are known to bind gangliosides. The genesis of anti-glycan antibodies in healthy humans and the reasons for their changes in pathologies are poorly understood. With a growing interest in their diagnostic applications, it is important to determine the carbohydrate structures that are recognized by antibodies present in the circulation of healthy individuals. We tested a large number of healthy donors using a printed glycan array (PGA) in a microchip format. The PGA contained ~300 glycans, representing mostly normal mammalian structures of glycoproteins and glycolipids, and many of the structures presented are biologically relevant sialylated motifs. As revealed by PGA, the sera interacted with at least 70 normal human glycans. With only few exceptions, antibodies recognizing sialosides have not been identified. Moderate levels of antibodies and moderate variability were observed in the case of SiaT n and its glycolyl variant. Unexpectedly, we found minimal antibody titer directed against Neu5Gc? and the trisaccharide Neu5Gc?2-6Gal?1-4GlcNAc, although this form of neuraminic acid does not occur naturally in humans. Antibodies recognizing sialosides in unnatural ?-configuration have been detected and confirmed Springer's paradigm that circulating antibodies represent a reaction against bacteria. Gram-negative bacteria contain LPS with ?KDN and/or ?KDO which are very close analogs of Neu5Ac that are found in ?-connected form. Antibodies against the biantennary N-glycan chain, (Neu5Ac?2-6Gal?1-4GlcNAc?1-2Man?)2-3,6-Man?1-4GlcNAc?1-4GlcNAc were never observed and similarly we never saw antibodies directed against the SiaLe(a)/SiaLe (x) motifs. Anti-sialoglycan antibodies can be masked with gangliosides: for example, we observe about a five times higher level of anti-GD3 in purified total IgG compared to the same concentration of total Ig in the composition of native serum. For several antibodies we observed anomalous binding in diluted sera, namely, the signals towards sialylated glycans were increased in the PGA if diluted sera were used. PMID:24037491

Shilova, Nadezhda; Huflejt, Margaret E; Vuskovic, Marko; Obukhova, Polina; Navakouski, Maksim; Khasbiullina, Nailya; Pazynina, Galina; Galanina, Oxana; Bazhenov, Alexey; Bovin, Nicolai

2013-09-14

176

Therapeutic Recombinant Monoclonal Antibodies  

ERIC Educational Resources Information Center

During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Bakhtiar, Ray

2012-01-01

177

The antiphospholipid antibody syndrome  

Microsoft Academic Search

The antiphospholipid antibody syndrome (APS) is the association of certain clinical features with the presence of antiphospholipid antibodies (APA) in the serum or plasma of affected individuals. APS may be primary or secondary to another disease, typically autoimmune diseases such as systemic lupus erythematosus (SLE).The prototypic clinical features are thrombotic events (venous and arterial) and pregnancy morbidity (recurrent fetal loss,

Michael C Nimmo; Cedric J Carter

2003-01-01

178

Production Of Human Antibodies  

NASA Technical Reports Server (NTRS)

Process for making human monoclonal antibodies based on combination of techniques. Antibodies made active against specific antigen. Process involves in vivo immunization of human B lymphocyte cells in mice. B cells of interest enriched in vitro before fusion. Method potentially applicable to any antigen. Does not rely on use of Epstein-Barr virus at any step. Human lymphocytes taken from any source.

Sammons, David W.; Neil, Garry A.

1993-01-01

179

Induction of antiphosphorylcholine antibody formation by anti-idiotypic antibodies.  

PubMed

Anti-idiotypic antibodies have been used to mimic antigen in the mouse antiphosphorylcholine response in order to investigate the induction of precursors of antibody-forming cells. We have shown that interaction of anti-idiotype antibody with receptor antibody molecules induces the formation of antibodies that are specific for phosphorylcholine and carry the idiotypic determinants. This induction is dependent on the recognition of carrier determinants on the anti-idiotype antibody by helper T cells. We conclude that receptor antibody molecules on the surface of the precursors of antibody-forming cells deliver the antigenic signal for the induction of these cells. PMID:53257

Trenkner, E; Riblet, R

1975-11-01

180

Red Blood Cell Antibody Identification  

MedlinePLUS

... Antibody ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin ... None The Test Sample What is being tested? Red blood cell antibodies are proteins produced by the ...

181

Antibodies for biodefense  

PubMed Central

Potential bioweapons are biological agents (bacteria, viruses and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US, following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases. PMID:22123065

Froude, Jeffrey W; Stiles, Bradley; Pelat, Thibaut

2011-01-01

182

A new method for isolation of human antisperm antibodies.  

PubMed

A study was undertaken to isolate pure human antisperm antibodies from the sera of infertile couples. One hundred infertile couples attending the Infertility and IVF Unit (Beilinson Medical Center) because of unexplained infertility were tested (both partners) for antisperm antibodies. Sixty-eight experiments were performed with positive sera containing antisperm antibodies and normal donor sperm. These experiments were followed by experiments in order to elute pure human antisperm antibodies from the sperm surface. Three experiments were performed with human sperm which were found to be coated by antisperm antibodies, in order to directly elute these antibodies from the sperm surface. In all experiments we eluted antisperm antibodies of the IgG and IgA isotypes from the sperm surface. These antibodies were demonstrated in the eluate, in each case by either the indirect immunobead test, the radial immune diffusion assay, or the electrophoresis method. Control experiments were performed as follows: (i) normal donor sperm incubated with normal serum; (ii) normal donor sperm without serum incubation; (iii) normal donor lymphocytes incubated with serum containing antisperm antibodies; (iv) normal donor lymphocytes without serum incubation. No antisperm antibodies were obtained in any of these control experiments. Absorption and elution experiments can be used for the isolation of pure human antisperm antibodies, which may then be used for the production of anti-idiotypic antibodies to antisperm antibodies. The anti-idiotypic antibodies could be further utilized as antigen substitutes for the production of a contraceptive vaccine and/or for application in the treatment of spontaneous abortion and infertility. PMID:8893096

Shohat, M; Hardy, B; Mannheimer, S; Fisch, B; Shohat, B

1996-01-01

183

Fetal arthrogryposis and maternal serum antibodies.  

PubMed

Arthrogryposis multiplex congenital (AMC) describes multiple joint contractures resulting from lack of movement in utero. Antibodies directed at the fetal isoform of the muscle acetylcholine receptor (AChR) have been reported in a small number of asymptomatic mothers of AMC babies. We examined sera from 179 mothers of AMC babies and 20 parous and non-parous controls to look for antibodies to AChR or undefined muscle or neuronal proteins. We found positive AChR antibodies in only three sera (1.5%) from asymptomatic AMC mothers. However, there was reactivity with muscle or with neuronal antigens in 33% of the sera, and reactivity to undefined neuronal antigens was more common in sera from mothers of AMC babies with CNS involvement (p=0.001) than those without. The offspring of mothers with AChR antibodies may benefit from treatment during pregnancy. Other maternal antibodies require further study, but these observations add to the emerging literature on maternal antibodies associated with developmental intrauterine disorders. PMID:16919948

Dalton, Paola; Clover, Linda; Wallerstein, Robert; Stewart, Helen; Genzel-Boroviczeny, Orsolya; Dean, Andrew; Vincent, Angela

2006-08-01

184

Fluorescence intensity positivity classification of Hep-2 cells images using fuzzy logic  

NASA Astrophysics Data System (ADS)

Indirect Immunofluorescence (IIF) is a good standard used for antinuclear autoantibody (ANA) test using Hep-2 cells to determine specific diseases. Different classifier algorithm methods have been proposed in previous works however, there still no valid set as a standard to classify the fluorescence intensity. This paper presents the use of fuzzy logic to classify the fluorescence intensity and to determine the positivity of the Hep-2 cell serum samples. The fuzzy algorithm involves the image pre-processing by filtering the noises and smoothen the image, converting the red, green and blue (RGB) color space of images to luminosity layer, chromaticity layer "a" and "b" (LAB) color space where the mean value of the lightness and chromaticity layer "a" was extracted and classified by using fuzzy logic algorithm based on the standard score ranges of antinuclear autoantibody (ANA) fluorescence intensity. Using 100 data sets of positive and intermediate fluorescence intensity for testing the performance measurements, the fuzzy logic obtained an accuracy of intermediate and positive class as 85% and 87% respectively.

Sazali, Dayang Farzana Abang; Janier, Josefina Barnachea; May, Zazilah Bt.

2014-10-01

185

Sputum direct fluorescent antibody (DFA)  

MedlinePLUS

Direct immunofluorescence test; Direct fluorescent antibody - sputum ... fluorescent dye are added to the sample. These antibodies are ... bright glow (fluorescence) can be seen in the sputum sample using ...

186

Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)  

SciTech Connect

Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-time PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.

Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena; Wurzbacher, Christian; Kurth, Reinhard; Denner, Joachim, E-mail: DennerJ@rki.d

2011-03-01

187

Role of Maternal Antibody in Natural Infection of Peromyscus maniculatus with Sin Nombre Virus  

Microsoft Academic Search

Data from naturally infected deer mice (Peromyscus maniculatus) were used to investigate vertical transmis- sion of Sin Nombre virus (SNV) and SNV-specific antibody. The antibody prevalence in juvenile mice (14 g or less) was inversely proportional to the mass of the animal, with juvenile deer mice weighing less than 11 g most likely to be antibody positive (26.9%) and juvenile

MONICA K. BORUCKI; JOHN D. BOONE; JOAN E. ROWE; MARLENE C. BOHLMAN; EDWARD A. KUHN; ROBERT DEBACA; STEPHEN C. S. T. JEOR

2000-01-01

188

Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications  

Microsoft Academic Search

Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy

A K Lefvert; K Bergström; G Matell; P O Osterman; R Pirskanen

1978-01-01

189

A microsphere immunoassay for detection of antibodies to avian influenza virus  

Microsoft Academic Search

A microsphere immunoassay (MIA) was developed for the detection of serum antibodies to avian influenza virus. A recombinant influenza A nucleoprotein expressed in baculovirus was conjugated to microspheres and incubated with antibodies. High median fluorescent intensities (MFIs) were obtained with a monoclonal antibody and positive chicken sera. Chickens were inoculated with 10 strains of avian influenza virus representing different subtypes,

Dirk Deregt; Tara L. Furukawa-Stoffer; Kara L. Tokaryk; John Pasick; Kimberley M. Burton Hughes; Kathleen Hooper-McGrevy; Shailja Baxi; Mohit K. Baxi

2006-01-01

190

Blue-Fluorescent Antibodies  

NASA Astrophysics Data System (ADS)

The forte of catalytic antibodies has resided in the control of the ground-state reaction coordinate. A principle and method are now described in which antibodies can direct the outcome of photophysical and photochemical events that take place on excited-state potential energy surfaces. The key component is a chemically reactive optical sensor that provides a direct report of the dynamic interplay between protein and ligand at the active site. To illustrate the concept, we used a trans-stilbene hapten to elicit a panel of monoclonal antibodies that displayed a range of fluorescent spectral behavior when bound to a trans-stilbene substrate. Several antibodies yielded a blue fluorescence indicative of an excited-state complex or ``exciplex'' between trans-stilbene and the antibody. The antibodies controlled the isomerization coordinate of trans-stilbene and dynamically coupled this manifold with an active-site residue. A step was taken toward the use of antibody-based photochemical sensors for diagnostic and clinical applications.

Simeonov, Anton; Matsushita, Masayuki; Juban, Eric A.; Thompson, Elizabeth H. Z.; Hoffman, Timothy Z.; Beuscher, Albert E.; Taylor, Matthew J.; Wirsching, Peter; Rettig, Wolfgang; McCusker, James K.; Stevens, Raymond C.; Millar, David P.; Schultz, Peter G.; Lerner, Richard A.; Janda, Kim D.

2000-10-01

191

Detection of anti-lactoferrin antibodies and anti-myeloperoxidase antibodies in autoimmune hepatitis: a retrospective study.  

PubMed

Anti-lactoferrin antibodies (ALA) and anti-myeloperoxidase antibodies (AMPA) are specific serological markers for autoimmune hepatitis (AIH). The project aimed to detect ALA and AMPA and explore their clinical significances in AIH patients. 59 AIH patients, 217 non AIH patients, and 50 healthy controls were enrolled in this study. ALA and AMPA were detected by ELISA. Antineutropil cytoplasmic antibodies (ANCA) and anti-smooth muscle antibodies (ASMA) were examined by indirect immunofluorescence. Antimitochondrial antibody M2 subtype (AMA-M2), anti-liver kidney microsomal antibody Type 1 (LKM1), anti-liver cytosol antibody Type 1 (LC1), and anti-soluble liver antigen/liver-pancreas antibodies (SLA/LP) were tested by immunoblot. The positivity for ALA was 18.6% in AIH group, only one patient in non-AIH group was positive for ALA; the positivity for AMPA was 59.3% in AIH group, with significant differences (P < 0.01) compared with other groups. The specificities for ALA and AMPA were 99.63% and 97.75%; the sensitivities were 18.64% and 59.32%; and the accuracy rates were 84.97% and 90.80%, respectively. A certain correlation was observed between ALA and SLA/LP, AMPA and ANCA, ASMA in AIH group. ALA and AMPA were associated with AIH, and had high clinical diagnostic value. Co-detection with other relative autoantibodies could play an important role in differential diagnosis of AIH. PMID:24547729

Tan, Liming; Zhang, Yuhong; Peng, Weihua; Chen, Juanjuan; Li, Hua; Ming, Feng

2014-01-01

192

Double positive CD4+CD8+ T cells: key suppressive role in the production of autoantibodies in systemic lupus erythematosus  

PubMed Central

Background & objectives: The presence of CD4+CD8+ (double positive) T cells (DPT) in the target organs of several autoimmune diseases has been reported. The aim of this study was to investigate the pathogenic role of DPT in systemic lupus erythematosus (SLE). Methods: A total of 175 SLE cases and 125 matched healthy controls were investigated for CD3+, CD4+, CD8+ lymphocytes and DPT by flow cytometry. Serum samples from SLE patients and controls were tested for antinuclear antibody (ANA), anti-double strain deoxyribonucleic acid (anti-dsDNA), anti-U1 ribonucleoprotein (anti-U1 RNP), anti-sjogren syndrome A (anti-SSA), anti-ribosomal P protein (anti-rib-P), anti-Smith (anti-Sm), anti-Sjogren syndrome B (anti-SSB), complement 3 (C3) and complement 4 (C4). Results: The DPT median and 5-95 per cent range of SLE cases and healthy controls were 0.50 [0.10-2.60] and 0.80 [0.20-2.74] respectively (P<0.001). SLE patients were divided into a ?1:1000 subgroup and a <1:1000 subgroup according to the ANA titre. The DPT of the former subgroup was significantly lower than that of the latter (P=0.032). The DPT medians of positive subgroups with anti-dsDNA (P<0.001), anti-U1RNP (P=0.018), anti-SSA (P=0.021) or anti-rib-P (P=0.039) were also significantly lower than the negative subgroups. Likewise, DPT was significantly lower in SLE subgroups with low concentration of C3 or C4 than those with high concentration (P<0.006). Interpretation & conclusions: Our findings show that the DPT cells may play a key suppressive role in the production of autoantibodies in SLE. Direct evidence that DPT regulates the pathogenesis of SLE needs to be investigated in future work. PMID:25488445

Wu, Yongkang; Cai, Bei; Feng, Weihua; Yang, Bin; Huang, Zhuochun; Zuo, Chuan; Wang, Lanlan

2014-01-01

193

Offered: Offered: Position(s): Position(s)  

E-print Network

, industrial, consumer, and portable electronics". The IC group produces power ICs for motor drivers, motor), industrial, automotive and portable electronics markets. Electrical Engineering No Entry LevelCompany: Industry: Website: Majors: Offered: Offered: Position(s): Position(s): Description

New Hampshire, University of

194

Antibodies to hnRNP core protein A1 in connective tissue diseases.  

PubMed

We investigated the specificity of circulating autoantibodies to a heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), obtained by recombinant DNA technique, in different rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, primary Sjogren's syndrome (SS), idiopathic Raynaud (IR), mixed connective tissue disease (MCTD), and healthy donors. All sera were tested by ELISA on hnRNP A1 protein. Positive values were obtained in 22% SLE, 19% scleroderma, 10% IR, 40% (2/5) MCTD, 5% SS, and 50% RA patients. The majority of patients reacted with the aminoterminal part (UP1) of hnRNP A1; however, some RA patients reacted also with the carboxy-terminal part that shows partial homology with keratin. Therefore, hnRNP A1 (UP1) can be considered a target of antinuclear autoimmunity in various rheumatic disorders. PMID:2745573

Astaldi Ricotti, G C; Bestagno, M; Cerino, A; Negri, C; Caporali, R; Cobianchi, F; Longhi, M; Maurizio Montecucco, C

1989-05-01

195

Bispecific Single Domain Antibodies  

Microsoft Academic Search

\\u000a Monoclonal antibodies are now widely recognized as therapeutic molecules and more than 25 molecules have been approved in\\u000a the United States and other countries. Despite these successes, the clinical activity of these molecules is still far from\\u000a optimal and new solutions have to be found, especially in the field of cancer therapy. The potential of bispecific antibodies,\\u000a capable of simultaneously

Patrick Chames; Daniel Baty

196

Antibody tumor penetration  

PubMed Central

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

2009-01-01

197

The significance of anti-streptokinase antibodies.  

PubMed Central

Antibodies to streptokinase (SK) are widespread in the population, but reports of their effect on the action of SK are conflicting. Specific anti-SK IgG was purified from the sera of 10 patients, five with low titres of anti-SK IgG and five with high titres. The effect of increasing specific anti-SK IgG antibodies on the action of SK was evaluated in vitro using a fluorimetric assay for plasmin and by a fibrin plate lysis assay. The inhibition of SK by whole plasma from a further group of patients was also assessed by the fibrin plate assay. There was a positive correlation between the serum antibody concentration and the quantity of specific anti-SK eluted (r = 0.797; P < 0.005). The addition of specific anti-SK IgG caused a dose-related decrease in SK activity (fluorimetric assay r = -0.93; P = 0.02; fibrin plate assay r = -0.98; P < 0.001). The addition of patient plasma to the fibrin plate assay also resulted in decreased lysis, which was dependent upon antibody titre (r = -0.95; P < 0.0001). Significant in vitro reduction of the activity of SK by specific antibody was demonstrated, and this was similar with plasma containing comparable amounts of antibody. The findings suggest that treatment with SK would be unlikely to induce an effective thrombolytic state when antibody titres are high (such as those seen within 2 years of an initial dose of SK). PMID:8004811

Lynch, M; Pentecost, B L; Littler, W A; Stockley, R A

1994-01-01

198

Structural Comparison of Different Antibodies Interacting with Parvovirus Capsids  

SciTech Connect

The structures of canine parvovirus (CPV) and feline parvovirus (FPV) complexed with antibody fragments from eight different neutralizing monoclonal antibodies were determined by cryo-electron microscopy (cryoEM) reconstruction to resolutions varying from 8.5 to 18 {angstrom}. The crystal structure of one of the Fab molecules and the sequence of the variable domain for each of the Fab molecules have been determined. The structures of Fab fragments not determined crystallographically were predicted by homology modeling according to the amino acid sequence. Fitting of the Fab and virus structures into the cryoEM densities identified the footprints of each antibody on the viral surface. As anticipated from earlier analyses, the Fab binding sites are directed to two epitopes, A and B. The A site is on an exposed part of the surface near an icosahedral threefold axis, whereas the B site is about equidistant from the surrounding five-, three-, and twofold axes. One antibody directed to the A site binds CPV but not FPV. Two of the antibodies directed to the B site neutralize the virus as Fab fragments. The differences in antibody properties have been linked to the amino acids within the antibody footprints, the position of the binding site relative to the icosahedral symmetry elements, and the orientation of the Fab structure relative to the surface of the virus. Most of the exposed surface area was antigenic, although each of the antibodies had a common area of overlap that coincided with the positions of the previously mapped escape mutations.

Hafenstein, Susan; Bowman, Valorie D.; Sun, Tao; Nelson, Christian D.S.; Palermo, Laura M.; Chipman, Paul R.; Battisti, Anthony J.; Parrish, Colin R.; Rossmann, Michael G.; Cornell; Purdue

2009-05-13

199

TSH receptor antibodies in autoimmune thyroiditis.  

PubMed

Out of 2,322 patients attending a thyroid clinic in north west Germany over a three year period, 123 were found to have evidence of autoimmune thyroiditis (hypothyroid, latent hypothyroid or euthyroid) and 96 were available for further analysis. TSH receptor antibodies (TRAb) were detectable by receptor assay in five of these patients (and a further two who attended the clinic later) and all the TRAb positive sera showed TSH blocking activity by bioassay. All of the patients with blocking activity were hypothyroid (on treatment) and represented 15% of this group of 34 patients. This suggests that in hypothyroid patients with autoimmune thyroiditis, the prevalence of TSH receptor antibodies with blocking activity is similar in northern Europe and Japan (21% of 43 patients; (1]. In the present study, no relationship between thyroid volume as assessed by sonography and the presence or absence of blocking antibodies was apparent. As blocking antibodies were undetectable in patients at early stages of the disease (i.e., in the euthyroid or latent hypothyroid groups) it seemed unlikely that these antibodies were a major causative factor in the development of hypothyroidism. PMID:3184158

Nordmeyer, J P; Hashim, F A; Shafeh, T; Eickenbusch, W; Rees Smith, B

1988-05-01

200

Antireticulin antibody: Incidence and diagnostic significance  

PubMed Central

Sera from 101 patients with adult coeliac disease, 46 patients with childhood coeliac disease, 50 patients with dermatitis herpetiformis, and 479 patients with various other diseases, including skin, gastrointestinal, haematological, and immunological disorders, have been tested for the presence of the antireticulin antibody. Positive sera were retested at higher dilutions. Antireticulin antibody was only found in a significant proportion of patients with three diseases, ie, coeliac disease, dermatitis herpetiformis, and Crohn's disease. Antireticulin antibody was present in 38 out of 101 patients (38%) with adult coeliac disease, 27 out of 46 patients (59%) with childhood coeliac disease, 11 out of 50 patients (22%) with dermatitis herpetiformis, and nine out of 38 patients (24%) with Crohn's disease. In the 434 other patients with various disorders the antireticulin antibody was present in only six 1·4%) (two patients were pregnant, one had vitiligo, one had tropical sprue, one had reticulum cell sarcoma, and one had pernicious anaemia). In patients with gluten-sensitive enteropathy, ie, coeliac disease and dermatitis herpetiformis, there was a significantly higher incidence in patients taking a normal diet compared with those on a gluten-free diet. The presence of antireticulin antibody would appear to be particularly helpful in diagnosing childhood coeliac disease as it was found in 22 out of 26 patients (85%) taking a normal diet. PMID:4574903

Seah, P. P.; Fry, Lionel; Holborow, E. J.; Rossiter, Mary A.; Doe, W. F.; Magalhaes, A. F.; Hoffbrand, A. V.

1973-01-01

201

Characterization and utilization of monoclonal antibodies reactive to Yersinia pseudotuberculosis.  

PubMed

The 3 murine monoclonal antibodies, Yps1, Yps2 and Yps3 reactive to Y. pseudotuberculosis can be stabilized and all were found to be of IgG type. Monoclonal antibody, Yps1, recognized a glycoprotein antigen of the organism with reactivity at the 55-75 kDa region, while Yps2 and Yps3 recognized protein antigens of Y. pseudotuberculosis 65 kDa and 26-28 kDa molecular weight regions, respectively. The specificity of monoclonal antibodies was tested using dot ELISA and Western blotting with whole cell organisms or whole cell sonicated soluble antigens of different Yersinia species, Salmonella typhi, Klebsiella pnemoniae, Streptococcus abortus-equi and Escherichia coli. Monoclonal antibody, Yps1 exhibited cross-reactivity with soluble antigens and whole cell preparations of Y. pestis. Yps2 cross-reacted to soluble antigens of all the tested bacteria. Reactivity of monoclonal antibody, Yps3 was restricted to Y. pseudotuberculosis and Y. pestis with soluble antigen preparations. No reaction was observed with Yps2 and Yps3 to whole cell organism preparations from tested bacteria including Y. pseudotuberculosis. The co-agglutination reagent prepared by sensitizing staphylococcal cells with Yps1 monoclonal antibody produced a positive agglutination with all the 4 Y. pseudotuberculosis isolates and the 3 Y. pestis strains tested. Sandwich dot ELISA using monospecific antisera as a capture antibody and a monoclonal antibody, and Yps3 as a revealing antibody had a high level of specificity in detecting Y. pseudotuberculosis antigens. PMID:15115097

Jain, Reena; Tuteja, Urmil; Batra, Harsh Vardhan

2003-12-01

202

Antibody informatics for drug discovery.  

PubMed

More and more antibody therapeutics are being approved every year, mainly due to their high efficacy and antigen selectivity. However, it is still difficult to identify the antigen, and thereby the function, of an antibody if no other information is available. There are obstacles inherent to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii) antibody numbering and IMGT. Here, we review "antibody informatics," which may integrate the above three fields so that bridging the gaps between industrial needs and academic solutions can be accelerated. This article is part of a Special Issue entitled: Recent advances in molecular engineering of antibody. PMID:25110827

Shirai, Hiroki; Prades, Catherine; Vita, Randi; Marcatili, Paolo; Popovic, Bojana; Xu, Jianqing; Overington, John P; Hirayama, Kazunori; Soga, Shinji; Tsunoyama, Kazuhisa; Clark, Dominic; Lefranc, Marie-Paule; Ikeda, Kazuyoshi

2014-11-01

203

Evaluation of monoclonal antibody-based capture enzyme immunoassays for detection of specific antibodies to measles virus.  

PubMed Central

Monoclonal antibodies to the hemagglutinin protein, fusion protein, phosphoprotein, matrix protein, and nucleoprotein of measles virus were evaluated as detector antibodies in capture enzyme immunoassays (EIAs) for the detection of specific serum immunoglobulin G (IgG), IgA, and IgM antibodies to measles virus. A pool of monoclonal antibodies to hemagglutinin protein and nucleoprotein proved optimal and was further evaluated. Specific IgM was detected in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of adolescents with clinical measles, 97% of infants 3 weeks postvaccination, and less than 1% of normal serum specimens. Specific IgA antibodies were found in 97% of clinical measles cases and vaccinees, in 26% of healthy persons, and in 36% of infants 8 months postvaccination; consequently, IgA antibodies were not a useful indicator of recent measles infection. A significant increase in IgG antibodies between paired specimens was detected in 92% of clinical cases and all vaccinees. Only 59% of infant specimens had persistent IgG antibodies as detected by capture EIA at 8 months postvaccination, whereas all specimens had antibodies as detected by hemagglutination inhibition and plaque neutralization. An alternative indirect EIA, in which antigen was directly absorbed to the solid phase, was more sensitive than the capture design, detecting IgG antibodies in all infants postvaccination. When standardized with a microneutralization assay for the detection of persistent antibodies, the indirect IgG EIA gave predictive values for positive and negative tests exceeding 90%. Our capture IgM and indirect IgG EIAs provide a practical combination of serologic tests for the determination of acute measles virus infection and past exposure to measles virus or vaccine, respectively. PMID:1885743

Erdman, D D; Anderson, L J; Adams, D R; Stewart, J A; Markowitz, L E; Bellini, W J

1991-01-01

204

Cross-reactive monoclonal antibodies for diagnosis of pneumococcal meningitis.  

PubMed Central

A diagnostic test for the detection of Streptococcus pneumoniae meningitis was developed using monoclonal antibodies (MAbs) to phosphocholine (PC) and non-PC determinants of pneumococcal teichoic acids. These MAbs do not recognize other bacteria that commonly cause meningitis. By using a dot blot assay, these MAbs were compared with a polyvalent pneumococcal capsular omniserum and an antiserum made to whole cells for their ability to detect pneumococci in infected spinal fluids. An immunoglobulin M (IgM) anti-PC antibody gave a positive reaction with 16 of 22 (73%) pneumococcal culture-positive spinal fluids. One false-positive result out of 45 pneumococcal culture-negative spinal fluids was also observed. D3114/63, an IgM MAb to non-PC determinants of teichoic acids, detected 15 of 22 of the pneumococcal culture-positive spinal fluids with one false-positive result. IgG2b and IgG3 anti-PC MAbs were less efficient than the IgM anti-PC MAb at detecting pneumococci in spinal fluids. Like the IgM anti-PC MAb, omniserum detected 73% of the culture-positive pneumococcal spinal fluids, with one false-positive result. The use of anti-PC or D3114/63 MAbs instead of a pooled serum such as omniserum has several advantages: (i) use of a single cross-reactive antibody rather than 83 pooled antibodies; (ii) possibility of a higher concentration of reactive antibody, which may increase the sensitivity of the test; (iii) a standardized antibody preparation; (iv) ease of preparation of the antibody; and (v) less expense. PMID:2460493

Waltman, W D; Gray, B; McDaniel, L S; Briles, D E

1988-01-01

205

Glycoproteomic Analysis of Antibodies*  

PubMed Central

Antibody glycosylation has been shown to change with various processes. This review presents mass spectrometric approaches for antibody glycosylation analysis at the level of released glycans, glycopeptides, and intact protein. With regard to IgG fragment crystallizable glycosylation, mass spectrometry has shown its potential for subclass-specific, high-throughput analysis. In contrast, because of the vast heterogeneity of peptide moieties, fragment antigen binding glycosylation analysis of polyclonal IgG relies entirely on glycan release. Next to IgG, IgA has gained some attention, and studies of its O- and N-glycosylation have revealed disease-associated glycosylation changes. Glycoproteomic analyses of IgM and IgE are lagging behind but should complete our picture of glycosylation's influence on antibody function. PMID:23325769

Zauner, Gerhild; Selman, Maurice H. J.; Bondt, Albert; Rombouts, Yoann; Blank, Dennis; Deelder, André M.; Wuhrer, Manfred

2013-01-01

206

An Antibody Molecule  

NSDL National Science Digital Library

An antibody molecule. (A) Schematic drawing of a typical antibody molecule. As indicated, this protein is Y-shaped and has two identical binding sites for its antigen, one on either arm of the 3Y.2 The protein is composed of four polypeptide chains (two identical heavy chains and two identical and smaller light chains) held together by disulfide bonds. Each chain is made up of several different domains, here shaded either blue or gray. The antigen-binding site is formed where a heavy chain variable domain (VH) and a light chain variable domain (VL) come close together. These are the domains that differ most in their sequence and structure in different antibodies. (B) Ribbon drawing of a light chain showing the parts of the VL domain most closely involved in binding to the antigen in red; these contribute half of the fingerlike loops that fold around each of the antigen molecules in (A).

Martin Raff

1998-07-01

207

Production of a monoclonal antibody specific for seminomas and dysgerminomas.  

PubMed Central

A monoclonal antibody (M2A, IgG2a) was produced against a cultured human ovarian epithelial adenocarcinoma cell line, HEY. Monoclonal antibody M2A reacted with a glycoprotein of molecular weight 40,000 on the surface of HEY cells. The affinity constant of the monoclonal antibody M2A for HEY cells was 10(9) M-1, and the number of binding sites on HEY cells was 2 X 10(4) per cell. The monoclonal antibody produced positive immunoperoxidase staining of fetal (but not adult) testis and of seminomas and dysgerminomas but did not stain various normal adult tissues or other gonadal or extragonadal tumors. Monoclonal antibody M2A may be useful for confirming a histological diagnosis of seminoma and dysgerminoma. Images PMID:3523489

Bailey, D; Baumal, R; Law, J; Sheldon, K; Kannampuzha, P; Stratis, M; Kahn, H; Marks, A

1986-01-01

208

Quantitative EMG of facial muscles in myasthenia patients with MuSK antibodies  

Microsoft Academic Search

ObjectiveOur aim was to study the pathophysiological process leading to facial muscle atrophy in 13 patients with MuSK antibody positive myasthenia gravis (MuSK-MG), and to compare with findings from 12 acetylcholine receptor antibody positive myasthenia patients (AChR-MG), selected because they suffered from the same degree of disease severity and required similar treatment.

Maria E. Farrugia; Robin P. Kennett; David Hilton-Jones; John Newsom-Davis; Angela Vincent

2007-01-01

209

Circulating microparticles in patients with antiphospholipid antibodies: Characterization and associations.  

PubMed

The antiphospholipid syndrome is characterized by venous or arterial thrombosis and/or recurrent fetal loss in the presence of circulating antiphospholipid antibodies. These antibodies cause activation of endothelial and other cell types leading to the release of microparticles with procoagulant and pro-inflammatory properties. The aims of this study were to characterize the levels of endothelial cell, monocyte or platelet derived, and tissue factor-bearing microparticles in patients with antiphospholipid antibodies, to determine the association of circulating microparticles with anticardiolipin and anti-?2-glycoprotein antibodies, and to define the cellular origin of microparticles that express tissue factor. Microparticle content within citrated blood from 47 patients with antiphospholipid antibodies and 144 healthy controls was analyzed within 2hours of venipuncture. Levels of Annexin-V, CD105 and CD144 (endothelial derived), CD41 (platelet derived) and tissue factor positive microparticles were significantly higher in patients than controls. Though levels of CD14 (monocyte-derived) microparticles in patient plasma were not significantly increased, increased levels of CD14 and tissue factor positive microparticles were observed in patients. Levels of microparticles that stained for CD105 and CD144 showed a positive correlation with IgG (R=0.60, p=0.006) and IgM anti-beta2-glycoprotein I antibodies (R=0.58, p=0.006). The elevation of endothelial and platelet derived microparticles in patients with antiphospholipid antibodies and their correlation with anti-?2-glycoprotein I antibodies suggests a chronic state of vascular cell activation in these individuals and an important role for ?2-glycoprotein I in development of the pro-thrombotic state associated with antiphospholipid antibodies. PMID:25467081

Chaturvedi, Shruti; Cockrell, Erin; Espinola, Ricardo; Hsi, Linda; Fulton, Stacey; Khan, Mohammad; Li, Liang; Fonseca, Fabio; Kundu, Suman; McCrae, Keith R

2015-01-01

210

Digital gangrene associated with anticentromere antibodies: a case report  

PubMed Central

Introduction Anticentromere antibodies have been associated with peripheral vascular occlusive disease, most frequently accompanied by sclerodactyly in the context of a connective tissue disorder. We report a case of digital gangrene with no other clinical associations except positive anticentromere antibodies. Case presentation Our patient, a 53-year-old Caucasian woman, non-smoker, presented with progressive pain and blackening of the distal right third finger over the preceding five weeks. No sclerodactyly was evident. She was anticentromere antibody positive at greater than 100 U/mL. Angiography revealed diffuse distal vasculopathy in both upper extremities. Other investigations were unremarkable. Conclusions It is rare for anticentromere antibody-associated digital necrosis to develop without concomitant sclerodactyly. However, this patient's case illustrates the need to consider an autoimmune contribution to the pathogenesis of digital ischemia even in the absence of a recognizable connective tissue disease. PMID:20569489

2010-01-01

211

Utility of feline coronavirus antibody tests.  

PubMed

Eight different tests for antibodies to feline coronavirus (FCoV) were evaluated for attributes that are important in situations in veterinary practice. We compared four indirect immunofluorescent antibody tests (IFAT), one enzyme-linked immunosorbent assay (ELISA) (FCoV Immunocomb; Biogal) and three rapid immunochromatographic (RIM) tests against a panel of samples designated by consensus as positive or negative. Specificity was 100% for all but the two IFATs based on transmissible gastroenteritis virus (TGEV), at 83.3% and 97.5%. The IFAT and ELISA tests were best for obtaining an antibody titre and for working in the presence of virus. The RIM tests were the best for obtaining a result quickly (10-15 mins); of these, the Speed F-Corona was the most sensitive, at 92.4%, followed by FASTest feline infectious peritonitis (FIP; 84.6%) and Anigen Rapid FCoV antibody test (64.1%). Sensitivity was 100% for the ELISA, one FCoV IFAT and one TGEV IFAT; and 98.2% for a second TGEV IFA and 96.1% for a second FCoV IFAT. All tests worked with effusions, even when only blood products were stipulated in the instruction manual. The ELISA and Anigen RIM tests were best for small quantities of sample. The most appropriate FCoV antibody test to use depends on the reason for testing: in excluding a diagnosis of FIP, sensitivity, specificity, small sample quantity, rapidity and ability to work in the presence of virus all matter. For FCoV screening, speed and sensitivity are important, and for FCoV elimination antibody titre is essential. PMID:24966245

Addie, Diane D; le Poder, Sophie; Burr, Paul; Decaro, Nicola; Graham, Elizabeth; Hofmann-Lehmann, Regina; Jarrett, Oswald; McDonald, Michael; Meli, Marina L

2015-02-01

212

Oral lichen planus with antibodies to desmogleins 1 and 3.  

PubMed

Lichen planus (LP) is a chronic inflammatory disorder involving the skin or mucous membranes. Previous studies have demonstrated that some LP patients showed positive enzyme-linked immunosorbent assay (ELISA) for desmoglein (DSG) antibodies. We report a case with intractable painful oral lesions. ELISA indices for DSG1 and 3 antibodies were increased by 49 and 36, respectively. Histopathological analysis revealed irregular acanthosis and band-like infiltration of lymphocytes at the dermal-epidermal interface. Direct immunofluorescence revealed negative deposits of immunoglobulin G and C3 in intracellular spaces of the epidermis. Indirect immunofluorescence of normal skin also did not detect any antibodies. Consequently, we made a final diagnosis of oral LP. The previous two LP cases with positive ELISA for DSG antibodies and our case manifested the erosive form, the most advanced oral LP. Therefore, it is a possibility that severe damage of keratinocytes may induce generation of DSG antibodies. However, negative results of immunofluorescence and no relation between disease severity and titers of antibodies make the possibility unlikely. We should measure titers of DSG antibodies in LP patients and accumulate data to establish a valid conclusion. PMID:25354571

Kinjyo, Chihiro; Kaneko, Takahide; Korekawa, Ayumi; Rokunohe, Akiko; Aizu, Takayuki; Matsuzaki, Yasushi; Nakano, Hajime; Sawamura, Daisuke

2015-01-01

213

Humanized Antibodies for Antiviral Therapy  

NASA Astrophysics Data System (ADS)

Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

Co, Man Sung; Deschamps, Marguerite; Whitley, Richard J.; Queen, Cary

1991-04-01

214

NMDA receptor antibodies associated with distinct white matter syndromes  

PubMed Central

Objective: To report the clinical and radiologic findings of children with NMDA receptor (NMDAR) antibodies and white matter disorders. Method: Ten children with significant white matter involvement, with or without anti-NMDAR encephalitis, were identified from 46 consecutive NMDAR antibody–positive pediatric patients. Clinical and neuroimaging features were reviewed and the treatment and outcomes of the neurologic syndromes evaluated. Results: Three distinct clinicoradiologic phenotypes were recognized: brainstem encephalitis (n = 3), leukoencephalopathy following herpes simplex virus encephalitis (HSVE) (n = 2), and acquired demyelination syndromes (ADS) (n = 5); 3 of the 5 with ADS had myelin oligodendrocyte glycoprotein as well as NMDAR antibodies. Typical NMDAR antibody encephalitis was seen in 3 patients remote from the first neurologic syndrome (2 brainstem, 1 post-HSVE). Six of the 7 patients (85%) who were treated acutely, during the original presentation with white matter involvement, improved following immunotherapy with steroids, IV immunoglobulin, and plasma exchange, either individually or in combination. Two patients had escalation of immunotherapy at relapse resulting in clinical improvement. The time course of clinical features, treatments, and recoveries correlated broadly with available serum antibody titers. Conclusion: Clinicoradiologic evidence of white matter involvement, often distinct, was identified in 22% of children with NMDAR antibodies and appears immunotherapy responsive, particularly when treated in the acute phase of neurologic presentation. When observed, this clinical improvement is often mirrored by reduction in NMDAR antibody levels, suggesting that these antibodies may mediate the white matter disease. PMID:25340058

Hacohen, Yael; Absoud, Michael; Hemingway, Cheryl; Jacobson, Leslie; Lin, Jean-Pierre; Pike, Mike; Pullaperuma, Sunil; Siddiqui, Ata; Wassmer, Evangeline; Waters, Patrick; Irani, Sarosh R.; Buckley, Camilla

2014-01-01

215

Prevalence of Antibodies to Hepatitis C Virus in Hemodialysis Patients  

Microsoft Academic Search

Due to frequent parenteral contact with blood transfusions hemodialysis patients are prone to acquire hepatitis C virus (HCV) infection. To determine the role of HCV infection we investigated the prevalence of antibodies to HCV in 188 hemodialysis patients. The prevalence of antibodies to HCV was 7.4%. As compared to anti-HCV-negative patients, anti-HCV-positive patients had slightly elevated transaminases which were independent

B. Kallinowski; L. Theilmann; K. Gmelin; K. Andrassy; D. Deppermann; B. Weinel; B. Kommerell

1991-01-01

216

Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity  

PubMed Central

Antibody capacity to recognize infectious virus is a prerequisite of many antiviral functions. We determined the infectious virion capture index (IVCI) of different antibody specificities. Whereas broadly neutralizing antibodies (bNAbs), except for an MPER bNAb, selectively captured infectious virions, non-bNAbs and mucosal human immunodeficiency virus type 1 (HIV-1)-positive IgG captured subsets of both infectious and noninfectious virions. Infectious virion capture was additive with a mixture of antibodies, providing proof of concept for vaccine-induced antibodies that together have improved capacity to recognize infectious virions. PMID:24554654

Liu, Pinghuang; Williams, LaTonya D.; Shen, Xiaoying; Bonsignori, Mattia; Vandergrift, Nathan A.; Overman, R. Glenn; Moody, M. Anthony; Liao, Hua-Xin; Stieh, Daniel J.; McCotter, Kerrie L.; French, Audrey L.; Hope, Thomas J.; Shattock, Robin; Haynes, Barton F.

2014-01-01

217

ANTIBODY PRODUCTION IN VITRO  

PubMed Central

The effects of actinomycin D and puromycin on spleen cell suspensions from rabbits immunized to SRC's were studied. These inhibitors, in high concentration, suppressed PFC's when added initially to recently isolated cells. When such cells were incubated for several days in the presence of both antigen and inhibitor, both actinomycin D and puromycin produced an increase in PFC's after the initial suppression. This recovery effect was best seen with cells from rabbits killed 3 days after boosting with SRC's, and was usually absent when cells were taken from rabbits killed 2 days after boosting. When actinomycin D or puromycin was added after several days in culture in the presence of SRC's, surviving PFC's were found to be not only resistant to these inhibitors, but there was also an increased number of PFC's compared to similar cultures incubated without these agents. Radioautographic studies showed that PFC's stimulated by the presence of actinomycin D or puromycin were not incorporating precursors for RNA or protein synthesis. In view of the known mode of action of these inhibitors, it was postulated that they were stimulating antibody production by PFC's in vitro either by interfering with represser mechanisms or stimulating the completion of antibody molecules, perhaps by causing the release of preformed antibody chains from ribosomes. Since the presence of specific antigens in vitro were necessary for these observed stimulatory effects on PFC's, and since antigens were producing an effect on antibody production on cells which were being suppressed by these inhibitors, added initially, it was further suggested that one role of antigen in the immune response was concerned with the completion of antibody synthesis on the ribosomes, perhaps by acting as an inducer as has been suggested previously (1). PMID:5642464

Harris, Gilmour

1968-01-01

218

Antibody-gold cluster conjugates  

DOEpatents

Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be about 5.0 nm. Methods and reagents are disclosed in which antibodies or Fab' fragments thereof are covalently bound to a stable cluster of gold atoms. 2 figs.

Hainfeld, J.F.

1988-06-28

219

Her2 Monoclonal Antibodies, Antibody Drug Conjugates, and Site Specific Antibody Conjugate Methods  

Cancer.gov

Antibody drug conjugates (ADC) can demonstrate high efficacy as cancer therapeutics, however, much more can be done to improve their efficacy and safety profile. Site-specific antibody drug conjugation is a promising way to do this.

220

Antibody Engineering and Therapeutics Conference  

PubMed Central

The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Biology), who will discuss a systems approach for studying disease that is enabled by emerging technology; Douglas Lauffenburger (Massachusetts Institute of Technology), who will discuss systems analysis of cell communication network dynamics for therapeutic biologics design; David Baker (University of Washington), who will describe computer-based design of smart protein therapeutics; and William Schief (The Scripps Research Institute), who will discuss epitope-focused immunogen design.   In this preview of the conference, the workshop and session chairs share their thoughts on what conference participants may learn in sessions on: (1) three-dimensional structure antibody modeling; (2) identifying clonal lineages from next-generation data sets of expressed VH gene sequences; (3) antibodies in cardiometabolic medicine; (4) the effects of antibody gene variation and usage on the antibody response; (5) directed evolution; (6) antibody pharmacokinetics, distribution and off-target toxicity; (7) use of knowledge-based design to guide development of complementarity-determining regions and epitopes to engineer or elicit the desired antibody; (8) optimizing antibody formats for immunotherapy; (9) antibodies in a complex environment; (10) polyclonal, oligoclonal and bispecific antibodies; (11) antibodies to watch in 2014; and (12) polyreactive antibodies and polyspecificity.

Almagro, Juan Carlos; Gilliland, Gary L; Scott, Jamie; Larrick, James W; Plückthun, Andreas; Veldman, Trudi; Adams, Gregory P; Parren, Paul WHI; Chester, Kerry A; Bradbury, Andrew; Reichert, Janice M; Huston, James S

2013-01-01

221

Fellowships & Positions  

Cancer.gov

Fellowships & Positions The NCI Division of Cancer Prevention is part of the National Institutes of Health (NIH), U.S. Department of Health and Human Services. Current Openings Position Title Number of Openings Cancer Prevention Fellowship Program

222

Nursing Positions  

MedlinePLUS

... breast with your other hand. The Clutch or Football Hold This is also a good position for ... same time may also choose this position. The football hold allows babies to take milk more easily — ...

223

[Antibody therapy for Alzheimer's disease].  

PubMed

In order to avoid Abeta-induced autoimmune encephalitis, several monoclonal and polyclonal antibodies are in clinical trials. These are bapineuzumab, solanezumab, ponezumab, gantenerumab, BAN2401, gammaguard and octagam. Since each antibody has a different antigen epitope of Abeta, anti-amyloid activities are different. It is unknown which antibody is effective for Alzheimer disease, and we must wait for the result of clinical trials. Some patients who developed tissue amyloid plaque immuno-reactive (TAPIR) antibody showed slower decline after AN-1792 vaccination. We developed TAPIR-like monoclonal antibody, which was found to react with Abeta oligomers preferentially. PMID:22277519

Tabira, Takeshi; Matsumoto, Shin-Ei; Jin, Haifeng

2011-11-01

224

Targeting antibodies to the cytoplasm  

PubMed Central

A growing number of research consortia are now focused on generating antibodies and recombinant antibody fragments that target the human proteome. A particularly valuable application for these binding molecules would be their use inside a living cell, e.g., for imaging or functional intervention. Animal-derived antibodies must be brought into the cell through the membrane, whereas the availability of the antibody genes from phage display systems allows intracellular expression. Here, the various technologies to target intracellular proteins with antibodies are reviewed. PMID:21099369

Marschall, Andrea L J; Frenzel, André; Schirrmann, Thomas; Schüngel, Manuela

2011-01-01

225

Transfer of Maternal Antibodies against Avian Influenza Virus in Mallards (Anas platyrhynchos)  

PubMed Central

Maternal antibodies protect chicks from infection with pathogens early in life and may impact pathogen dynamics due to the alteration of the proportion of susceptible individuals in a population. We investigated the transfer of maternal antibodies against avian influenza virus (AIV) in a key AIV host species, the mallard (Anas platyrhynchos). Combining observations in both the field and in mallards kept in captivity, we connected maternal AIV antibody concentrations in eggs to (i) female body condition, (ii) female AIV antibody concentration, (iii) egg laying order, (iv) egg size and (v) embryo sex. We applied maternity analysis to the eggs collected in the field to account for intraspecific nest parasitism, which is reportedly high in Anseriformes, detecting parasitic eggs in one out of eight clutches. AIV antibody prevalence in free-living and captive females was respectively 48% and 56%, with 43% and 24% of the eggs receiving these antibodies maternally. In both field and captive study, maternal AIV antibody concentrations in egg yolk correlated positively with circulating AIV antibody concentrations in females. In the captive study, yolk AIV antibody concentrations correlated positively with egg laying order. Female body mass and egg size from the field and captive study, and embryos sex from the field study were not associated with maternal AIV antibody concentrations in eggs. Our study indicates that maternal AIV antibody transfer may potentially play an important role in shaping AIV infection dynamics in mallards. PMID:25386907

van Dijk, Jacintha G. B.; Mateman, A. Christa; Klaassen, Marcel

2014-01-01

226

Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas  

PubMed Central

We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-?) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-? and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-? test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-? test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-? positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-? test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations. PMID:22914362

Holder, Tom; Clifford, Derek; Dexter, Ian; Brewer, Jacky; Smith, Noel; Waring, Laura; Crawshaw, Tim; Gillgan, Steve; Lyashchenko, Konstantin; Lawrence, John; Clarke, John; de la Rua-Domenech, Ricardo; Vordermeier, Martin

2012-01-01

227

Commercial antibodies and their validation  

PubMed Central

Despite an impressive growth in the business of research antibodies a general lack of trust in commercial antibodies remains in place. A variety of issues, each one potentially causing an antibody to fail, underpin the frustrations that scientists endure. Lots of money goes to waste in buying and trying one failing antibody after the other without realizing all the pitfalls that come with the product: Antibodies can get inactivated, both the biological material and the assay itself can potentially be flawed, a single antibody featuring in many different catalogues can be deemed as a set of different products, and a bad choice of antibody type, wrong dilutions, and lack of proper validation can all jeopardize the intended experiments. Antibodies endorsed by scientific research papers do not always meet the scientist’s requirements either due to flawed specifications, or due to batch-to-batch variations. Antibodies can be found with Quality Control data obtained from previous batches that no longer represent the batch on sale. In addition, one cannot assume that every antibody is fit for every application. The best chance of success is to try an antibody that already was confirmed to perform correctly in the required platform. PMID:25324967

Voskuil, JLA

2014-01-01

228

Therapeutic antibodies against cancer  

PubMed Central

Antibody-based therapeutics against cancer are highly successful in clinic and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States (one, mylotarg, was withdrawn from market in 2010). Three of the mAbs (bevacizumab, rituximab, trastuzumab) are in the top six selling protein therapeutics with sales in 2010 of more than $5 bln each. Hundreds of mAbs including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs and mAbs with optimized pharmacokinetics are in clinical trials. However, challenges remain and it appears that deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems and individual variations. PMID:22520975

Adler, Mark J.; Dimitrov, Dimiter S.

2012-01-01

229

Antibody-mediated radiotherapy  

SciTech Connect

Antibodies that react with antigens on the surface of tumor cells but not normal cells have great potential for cancer detection and therapy. If radiolabeled without loss of immunologic specificity, such antibodies may be able to deliver cytoxic amounts of radiation. Target- cell specificity and a high extraction coefficient are necessary with any radionuclide in order to minimize normal tissue irradiation. Tumor- cell-retention time and the rate of catabolized radionuclide will also influence ultimate applicability. Among the unanswered questions for choosing a radionuclide is the choice of particle emitter. Although classic beta emitters have been used in a number of clinical situations, they have not had a major impact on disease outcome except in diseases of the thyroid. Unfortunately, Auger emitters such as iodine 125 are cytotoxic only when localized within close proximity to the genome. On the other hand, alpha emitters such as astatine 211 eliminate the need for subcellular sequestration but not cell-specific localization. 34 references.

Bloomer, W.D.; Lipsztein, R.; Dalton, J.F.

1985-05-01

230

Antibodies to heteromeric glycolipid complexes in multifocal motor neuropathy  

PubMed Central

Background Measurement of anti-GM1 IgM antibodies in multifocal motor neuropathy (MMN) sera is confounded by relatively low sensitivity that limits clinical usefulness. Combinatorial assay methods, in which antibodies reactive to heteromeric complexes of 2 or more glycolipids are being increasingly applied to this area of diagnostic testing. Methods A newly developed combinatorial glycoarray able to identify antibodies to 45 different heteromeric glycolipid complexes and their 10 individual glycolipid components was applied to a randomly selected population of 33 MMN cases and 57 normal or disease controls. Comparison with an enzyme-linked immunosorbent assay (ELISA) was conducted for selected single glycolipids and their complexes. Results By ELISA, 22/33 MMN cases had detectable anti-GM1 IgM antibodies, whereas 19/33 MMN samples were positive for anti-GM1 antibodies by glycoarray. Analysis of variance (ANOVA) revealed that of the 55 possible single glycolipids and their 1:1 complexes, antibodies to the GM1:galactocerebroside (GM1:GalC) complex were most significantly associated with MMN, returning 33/33 MMN samples as positive by glycoarray and 29/33 positive by ELISA. Regression analysis revealed a high correlation in absolute values between ELISA and glycocarray. Receiver operator characteristic (ROC) analysis revealed insignificantly different diagnostic performance between the two methods, although at the lower end of sensitivity, the glycoarray appeared slightly advantageous by identifying antibodies in 4 ELISA-negative samples. Conclusions The use of combinatorial glycoarray or ELISA increased the diagnostic sensitivity of anti-glycolipid antibody testing in this cohort of MMN cases, without significantly affecting specificity, and may be a useful assay modification for routine clinical screening. PMID:22727042

Galban-Horcajo F, Francesc; Fitzpatrick, Amanda M.; Hutton, Andrew J.; Dunn, Siobhan M.; Kalna, Gabriela; Brennan, Kathryn M.; Rinaldi, Simon; Yu, Robert K.; Goodyear, Carl; Willison, Hugh J.

2013-01-01

231

Antibody screening in multitransfused patients: A prerequisite before each transfusion.  

PubMed

Life-long red blood cell (RBC) transfusions remain the main treatment for severe thalassemia. We hereby report a case of anti S and anti Lu(a) in a ?-thalassemia major patient detected incidentally on antibody screening. The patient was a known case of ?-thalassemia major and was on regular blood transfusion every 3 weeks from the institute from the age of 6 months. Subsequently, on one occasion, patient's crossmatch was compatible despite positive antibody screen using microcolumn gel technique. Autocontrol and direct antiglobulin test were negative on microcolumn gel. Anti S and anti Lu(a) antibodies were identified. Blood unit found compatible was negative for S and Lu(a) antigens. Antibody titers were 1:1 for both anti S and anti Lu(a) in AHG phase using tube technique and antibodies were of IgG type. Blood unit was transfused uneventfully to the patient. Donors were traced back (last three donations) and called for repeat blood sample testing for S and Lu(a) antigen. Two out of three donors were found to be S antigen positive and one out of these two was Lu(a) antigen positive. Anti S and anti Lu(a) antibodies were again identified on patient's subsequent visit for transfusion. The present case re-emphasize the importance of antibody screening at each visit in earlier detection of antibodies in multi transfused patients. Encouraging patients to receive transfusion from one center and dedicating donors could reduce alloimmunization rate but larger studies are required. PMID:25294114

Lamba, Divjot S; Mittal, Kshitija; Sood, Tanvi; Bedi, Ravneet Kaur; Kaur, Paramjit; Kaur, Gagandeep

2014-10-01

232

Antibody development to Fusobacterium necrophorum in patients with peritonsillar abscess.  

PubMed

A polymicrobial mixture of aerobic and anaerobic bacteria is commonly recovered from peritonsillar abscess (PTA) aspirates. Previous studies have suggested a role for Fusobacterium necrophorum (FN) in the development of PTA. The purpose of the current study was to explore whether anti-FN antibodies were produced in patients with PTA. We developed a novel immunofluorescence-based method to measure anti-FN antibody levels in acute and convalescent sera from 15 patients with PTA and 47 patients with chronic tonsillar conditions (controls) undergoing acute or elective tonsillectomy, respectively. Bacterial cultures were performed on tonsillar cores and surfaces, pus aspirates, and blood. An increase in anti-FN antibody levels (of at least doubling of the previous level) was observed in 8 of 11 (73 %) PTA patients with FN-positive pus aspirate cultures (FN-positive patients). In contrast, the four FN-negative PTA patients did not have an increase in anti-FN antibody levels (p?=?0.026). The change in anti-FN antibody levels in FN-positive PTA patients was also significantly greater than that for FN-positive electively tonsillectomized patients (p?=?0.0014) and all electively tonsillectomized patients (p?

Klug, T E; Henriksen, J-J; Rusan, M; Fuursted, K; Krogfelt, K A; Ovesen, T; Struve, C

2014-10-01

233

Pseudomonas infection in antibody deficient patients  

PubMed Central

Pseudomonas aeruginosa (PA) is commonly isolated from the respiratory secretions of antibody deficiency patients, but the significance of this has not been well studied. We have reviewed our adult antibody deficiency cohort of 179 patients and assessed the prevalence and characteristics of PA infection and the effects of early antibiotic eradication treatments. Of the 34 patients with PA, 55.9% (19) underwent successful eradication and were infection-free, 38.2% (13) had intermittent infection, and 5.9% (2) had chronic PA. PA infection was significantly associated with bronchiectasis (p < 0.0001), with 36.1% (22 out of 61) of patients with bronchiectasis developing a PA infection. Infection status was also significantly associated with chronic sinusitis (p < 0.0001). Most treated PA exacerbations were symptomatic and with colony counts of ?1000 cfu/ml. Current eradication protocols used at our center involve early treatment at first positive isolate with ciprofloxacin for 3 weeks and nebulized colomycin for 3 months, and if eradication fails, intravenous ceftazidime and gentamycin or colomycin is administered for 2 weeks. Continued sputum surveillance and early eradication treatments upon positive PA culture may help to limit chronic PA infection in antibody deficiency patients.

Duraisingham, Sai S.; Hanson, Steven; Buckland, Matthew; Grigoriadou, Sofia

2014-01-01

234

Detection of antibody to murine cytomegalovirus by enzyme-linked immunosorbent and indirect immunofluorescence assays.  

PubMed Central

We have compared murine cytomegalovirus (MCMV) antibody determination by enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. A comparison of antibody detection with 146 serum samples at a 1:20 dilution showed 100% agreement (60 negatives and 86 positives) between the assays. There was close agreement of endpoint determinations of sera by both methods. After experimental MCMV infection, antibody to MCMV was detected by both assays as early as day 7, and high titers persisted as late as 6 months. In contrast to immunocompetent littermates, athymic nude mice did not develop antibody after infection. Mice lacking antibody detectable by ELISA were susceptible to lethal MCMV challenge. In a survey of animals from five commercial sources, MCMV antibody was not detected unless mice were experimentally infected. MCMV antibody determination by ELISA is a convenient method, comparable to the indirect immunofluorescence assay in sensitivity and specificity. PMID:3033015

Classen, D C; Morningstar, J M; Shanley, J D

1987-01-01

235

Antibody Therapy for Pediatric Leukemia  

PubMed Central

Despite increasing cure rates for pediatric leukemia, relapsed disease still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. Antibody therapies represent a form of targeted therapy that offers a new treatment paradigm. Monoclonal antibodies are active in pediatric acute lymphoblastic leukemia (ALL) and are currently in Phase III trials. Antibody-drug conjugates (ADCs) are the next generation of antibodies where a highly potent cytotoxic agent is bound to an antibody by a linker, resulting in selective targeting of leukemia cells. ADCs are currently being tested in clinical trials for pediatric acute myeloid leukemia and ALL. Bispecific T cell engager (BiTE) antibodies are a construct whereby each antibody contains two binding sites, with one designed to engage the patient’s own immune system and the other to target malignant cells. BiTE antibodies show great promise as a novel and effective therapy for childhood leukemia. This review will outline recent developments in targeted agents for pediatric leukemia including monoclonal antibodies, ADCs, and BiTE antibodies. PMID:24795859

Vedi, Aditi; Ziegler, David S.

2014-01-01

236

The prevalence of anti-acetylcholinesterase antibodies in autoimmune disease.  

PubMed

A robust and precise enzyme linked immunosorbent assay (ELISA) with proven sensitivity and specificity has been employed to detect human antibodies (allogenic/autogenic) to human acetylcholinesterase (AChE). The sensitivity of the method has been established using mouse monoclonal antibodies (0.8 ng/ml) and uniquely, human sera positive for anti-Yt(a) allogenic antibodies, to one phenotypic form (most common) of human AChE. The latter was also used as the positive human control to ensure functionality of the assay. The ELISA method was used to establish a normal distribution curve for absorbance values employing sera from healthy blood donors Subsequently, the ELISA was employed to investigate the prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease and patients with non-autoimmune thyroid disease (diseased control). The results indicate that there is not a high prevalence of anti-AChE antibodies in patients with confirmed autoimmune disease. The lack of anti-AChE autoantibodies in patients' with clinically apparent Graves' ophthalmopathy, mitigates against there being a causal role of such antibodies in Graves' associated eye disease. PMID:15763920

Geen, J; Howells, R C; Ludgate, M; Hullin, D A; Hogg, S I

2004-12-01

237

Immunofluorescent antibody test for diagnosis of gonorrhoea.  

PubMed Central

An indirect fluorescent antibody test was evaluated in 198 cases of a high-risk group with a culture prevalence of 37.3% and in 426 cases of a low-risk group with a culture prevalence of 1.16%. A sensitivity of 77.1% in the culture-positive patients with uncomplicated gonorrhoea, and a specificity of 88.7% in the culture- and history-negative cases, was obtained in the high-risk group. In this group, the sera from 88.8% of the patients with culture-proven gonorrhoea became positive in an indirect fluorescent antibody test within 3 weeks of last sexual contact. In the low-risk group, for which the sensitivity could not be determined due to various reasons, a specificity of 95.8% was obtained. Complement fixation test was positive in sera of only 17.6% of the culture-positive cases of the high-risk group. PMID:809468

Caloenescu, M; Clecner, B; Petrow, S; Kasatiya, S S

1975-01-01

238

Satellite positioning  

NASA Technical Reports Server (NTRS)

Developments in satellite positioning techniques and their applications are reviewed on the basis of the theoretical and practical work published by U.S. researchers in 1987-1990. Current techniques are classified into two main categories: satellite laser tracking and radio tracking. Particular attention is given to the Geoscience Laser Ranging System, the Lunar Laser Ranging concept; GPS ephemerides determination, fiducial networks, and reference frame; static GPS positioning; and kinematic GPS positioning.

Colombo, Oscar L.; Watkins, Michael M.

1991-01-01

239

Indirect ELISA and indirect immunofluorescent antibody assay for detecting the antibody against murine norovirus S7 in mice.  

PubMed

To evaluate murine norovirus (MNV) infection in laboratory mice, we attempted to develop an enzyme-linked immunosorbent assay (ELISA) system and an indirect immunofluorescent antibody (IFA) assay for detecting the anti-MNV-S7 antibody in mice. MNV-S7, which was isolated in Japan, was used in both assays. The antigen for ELISA was prepared by ultracentrifugation of culture supernatants of RAW 264 cells infected with MNV-S7. Positive sera were obtained from 6-week-old, female C57BL/6JJcl mice inoculated orally with MNV-S7. IFA against infected RAW 264 cells was able to discriminate positive sera from negative sera. Indirect ELISA was performed using 96-well ELISA plates coated with formalin-treated MNV-S7 antigen. In this ELISA system, mouse sera obtained 2 weeks after infection or later showed significantly high OD values and were judged positive. An equal level of anti-MNV-S7 antibody response was observed in BALB/cAJcl, C57BL/6JJcl, DBA/2JJcl, and Jcl:ICR mice; whereas, C3H/HeJJcl mice demonstrated slightly lower antibody production 4 weeks after infection. We also used this ELISA system to evaluate 77 murine serum samples obtained from 15 conventional mouse rooms in research facilities in Japan and found that approximately half of the serum samples contained antibody to MNV-S7. We found that some serum samples were negative for antibodies to mouse hepatitis virus and Mycoplasma pulmonis but positive for antibody to MNV-S7. The results suggest that the MNV infection is more prevalent than other infections such as mouse hepatitis virus and Mycoplasma pulmonis in conventional mouse colonies in Japan, as is the case in other areas of the world. PMID:20224169

Kitagawa, Yota; Tohya, Yukinobu; Ike, Fumio; Kajita, Ayako; Park, Sang-Jin; Ishii, Yoshiyuki; Kyuwa, Shigeru; Yoshikawa, Yasuhiro

2010-01-01

240

Antibody-mediated immunity against tuberculosis: implications for vaccine development.  

PubMed

There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity of antibody responses to mycobacteria, and address mechanism of protection. Based on these findings and discussions, we challenge the common belief that immunity against M. tuberculosis relies solely on cellular defense mechanisms, and posit that induction of antibody-mediated immunity should be included in TB vaccine development strategies. PMID:23498951

Achkar, Jacqueline M; Casadevall, Arturo

2013-03-13

241

Antibody-Mediated Immunity against Tuberculosis: Implications for Vaccine Development  

PubMed Central

There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity of antibody responses to mycobacteria, and address mechanism of protection. Based on these findings and discussions, we challenge the common belief that immunity against M. tuberculosis relies solely on cellular defense mechanisms, and posit that induction of antibody-mediated immunity should be included in TB vaccine development strategies. PMID:23498951

Achkar, Jacqueline M.; Casadevall, Arturo

2013-01-01

242

Leucine-rich glioma-inactivated protein 1 antibody encephalitis  

PubMed Central

Objective: To describe a case of leucine-rich glioma-inactivated protein 1 (LGI1) antibody–associated encephalitis. Methods: The clinical and ancillary data and brain MRIs were gathered retrospectively by chart review. Relevant literature on similar cases was also reviewed. Results: The diagnosis of LGI1 antibody–associated autoimmune encephalitis was based on the typical clinical presentation of seizures, psychiatric symptoms, and memory loss as well as negative diagnostic testing for cancer; the diagnosis was confirmed by positive LGI1 antibody. The patient responded favorably to treatment with IV immunoglobulin and continues to do well. Conclusion: LGI1 antibody–associated encephalitis has increasingly been recognized as a primary autoimmune disorder with good prognosis and response to treatment. PMID:25520958

Mayasi, Yunis; Takhtani, Deepak

2014-01-01

243

Automated Instrument for the Fluorescent Treponemal Antibody-Absorption Test and Other Immunofluorescence Tests  

PubMed Central

An automated diagnostic test instrument and its development program are described. The instrument automates the fluorescent treponemal antibody-absorption test for syphilis to the extent that only 4 hr of technician time is required to conduct approximately 200 tests daily. Evaluation to date suggests its efficacy. In addition, preliminary studies indicate the feasibility of detecting antibodies to Toxoplasma gondii, Plasmodium malariae, and nucleoprotein (antinuclear factor). The instrument would seem to have broad application for routine and research immunofluorescence testing. Two elements comprise the instrument: a slide processor and a microscope attachment. The slide processor is an electro-pneumatically actuated device which automatically feeds special laboratory slides, on which antigen or other reagents are prefixed, through a series of operations which provide reagent application, incubation, washing, drying, and stacking of the finished slides for readout. The instrument provides flexibility in that incubation time and temperature as well as point, sequence, and duration of reagent application can be varied to accommodate a variety of immunofluorescence techniques. The microscope attachment can be fitted to all conventional dark-field fluorescence microscopes and makes possible the reading of three to six slides per minute. The reacted slides from the processor are injected sequentially onto the stage of the microscope by movement of a lever. As injected, slides are automatically in visual focus; fine focus is occasionally required. Scanning of the reacted field is accomplished by means of the normal microscope controls. A buffered glycerol coupling is maintained between the darkfield condenser substage lens and the slide cover glass by means of a pushbutton-actuated feed system. Images PMID:4905605

Binnings, Gerald F.; Riley, Mel J.; Roberts, Merritt E.; Barnes, Richard; Pringle, Thomas C.

1969-01-01

244

Antibody biodistribution coefficients  

PubMed Central

Tissue vs. plasma concentration profiles have been generated from a physiologically-based pharmacokinetic model of monoclonal antibody (mAb). Based on the profiles, we hypothesized that a linear relationship between the plasma and tissue concentrations of non-binding mAbs could exist; and that the relationship may be generally constant irrespective of the absolute mAb concentration, time, and animal species being analyzed. The hypothesis was verified for various tissues in mice, rat, monkey, and human using mAb or antibody-drug conjugate tissue distribution data collected from diverse literature. The relationship between the plasma and various tissue concentrations was mathematically characterized using the antibody biodistribution coefficient (ABC). Estimated ABC values suggest that typically the concentration of mAb in lung is 14.9%, heart 10.2%, kidney 13.7%, muscle 3.97%, skin 15.7%, small intestine 5.22%, large intestine 5.03%, spleen 12.8%, liver 12.1%, bone 7.27%, stomach 4.98%, lymph node 8.46%, adipose 4.78%, brain 0.351%, pancreas 6.4%, testes 5.88%, thyroid 67.5% and thymus is 6.62% of the plasma concentration. The validity of using the ABC to predict mAb concentrations in different tissues of mouse, rat, monkey, and human species was evaluated by generating validation data sets, which demonstrated that predicted concentrations were within 2-fold of the observed concentrations. The use of ABC to infer tissue concentrations of mAbs and related molecules provides a valuable tool for investigating preclinical or clinical disposition of these molecules. It can also help eliminate or optimize biodistribution studies, and interpret efficacy or toxicity of the drug in a particular tissue. PMID:23406896

Shah, Dhaval K.; Betts, Alison M.

2013-01-01

245

Antibody Production by Single Cells  

Microsoft Academic Search

FAGREUS1 and others2,3 have shown that certain tissues from pre-sensitized animals can form antibody in vitro. This communication describes a technique whereby antibody production by single cells isolated in microdroplets can be detected. The technique is based on specific immobilization of Salmonella serotypes by anti-flagellar antibody. It was observed that single cells from a rat, simultaneously stimulated with two antigens,

G. J. V. Nossal; Joshua Lederberg

1958-01-01

246

Function-first antibody discovery  

PubMed Central

Therapeutic antibodies may mediate antineoplastic effects by altering the biological functions of their target, by directly stimulating the demise of cancer cells or by activating antibody-dependent immune effector mechanisms. We have recently provided in vivo proof-of-concept for a “function-first” target and drug discovery platform in which antibodies against a multitude of tumor-associated antigens are screened for biological effects in a target-unbiased manner. PMID:24083074

Frendéus, Björn

2013-01-01

247

Monoclonal antibody therapy of cancer  

Microsoft Academic Search

The most significant recent advances in the application of monoclonal antibodies (mAbs) to oncology have been the introduction and approval of bevacizumab (Avastin), an anti–vascular endothelial growth factor antibody, and of cetuximab (Erbitux), an anti–epidermal growth factor antibody. In combination with standard chemotherapy regimens, bevacizumab significantly prolongs the survival of patients with metastatic cancers of the colorectum, breast and lung.

Gregory P Adams; Louis M Weiner

2005-01-01

248

Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton  

PubMed Central

Objective: To examine the clinical features of pediatric CNS demyelination associated with positive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects of MOG antibody on oligodendrocyte cytoskeleton. Methods: We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3–15.3) followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on oligodendrocyte cytoskeleton using 3D deconvolution imaging. Results: MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first presentation, MOG antibody–positive patients were more likely to have bilateral than unilateral optic neuritis (ON) (9/10 vs 1/5, respectively, p = 0.03), less likely to have brainstem findings (2/31 vs 16/42, p = 0.005), more likely to have a raised erythrocyte sedimentation rate >20 mm/h (9/19 vs 3/21, p = 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p = 0.18), and less likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, p = 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON most likely to be seropositive. Two relapsing MOG antibody–positive patients treated with mycophenolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes incubated with purified IgG from MOG antibody–positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and ?-tubulin immunolabelings. Conclusions: MOG antibody may define a separate demyelination syndrome, which has therapeutic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton. PMID:25340056

Dale, Russell C.; Tantsis, Esther M.; Merheb, Vera; Kumaran, Raani-Yogeeta A.; Sinmaz, Nese; Pathmanandavel, Karrnan; Ramanathan, Sudarshini; Booth, David R.; Wienholt, Louise A.; Prelog, Kristina; Clark, Damien R.; Guillemin, Gilles J.; Lim, Chai K.; Mathey, Emily K.

2014-01-01

249

Comparison of monoclonal versus polyclonal calretinin antibodies for immunohistochemical diagnosis of malignant mesothelioma.  

PubMed

Of putative specific markers for diffuse malignant mesothelioma, nuclear staining with Zymed polyclonal calretinin antibody has shown the best specificity to date for epithelial diffuse malignant mesothelioma versus adenocarcinoma. We compared specificity and sensitivity of this polyclonal antibody for diagnosis of diffuse malignant mesothelioma with a new monoclonal antibody from DAKO. One hundred eighteen adenocarcinomas and 111 diffuse malignant mesotheliomas-70 epithelial, 22 sarcomatous, and 19 biphasic-were immunostained with calretinin antibodies from Zymed (polyclonal rabbit, prediluted, PAD:DC8) and DAKO(monoclonal mouse, 1:100, clone DAK Calret 1) using manufacturer-recommended procedures. Cases were blinded and assessed for nuclear versus cytoplasmic staining, percent positive cells, and background. Both antibodies showed similar positive predictive values for diffuse malignant mesothelioma by nuclear staining (Zymed=95%; DAKO=97%). False positives in 4 (3.4%) and 2 (1.7%) adenocarcinomas, respectively, stained greater than 10% of cells. Sensitivity for epithelial malignant mesothelioma was slightly less for DAKO antibody (Zymed=80%; DAKO=73%). Neither antibody performed well on sarcomatous malignant mesothelioma (Zymed=2/22; DAKO=1/22). Both antibodies are useful in the diagnosis of epithelial malignant mesothelioma, although monoclonal antibody is slightly less sensitive. PMID:15722797

Granville, Laura A; Younes, Mamoun; Churg, Andrew; Roggli, Victor L; Henderson, Douglas W; Cagle, Philip T

2005-03-01

250

Screening Autoimmune Anti-neuronal Antibodies in Pediatric Patients with Suspected Autoimmune Encephalitis  

PubMed Central

Background and Purpose: The aim of this study was to identify and describe the pediatric autoimmune encephalitis cases positive for anti-neuronal antibody tests. Methods: Screening of six anti-neuronal antibodies in 23 children with suspected autoimmune encephalitis was performed by cell-based indirect immunofluorescence test with patients’ serum or cerebrospinal fluid. Results: Among the 23 cases enrolled here, eight patients (35%) were positive for the anti-N-methyl-d-aspartate (NMDA) receptor antibody and one patient (4%) was positive for the anti-contactin-associated protein-like 2 (CASPR2) antibody. In the anti-NMDA receptor antibody-positive group, seizure and movement disorders were the most prominent features and were present in all patients. A tumor was present in only one patient. Three patients with infant- and toddler-onset disease did not exhibit a classic multistage illness. In addition to seizure and dyskinesia, aphasia or mutism without severe consciousness impairment was present in all three patients. These atypical clinical presentations may suggest different pathomechanism of anti-NMDA receptor encephalitis among these age groups. The patient who was positive for the anti-CASPR2 antibody was an 8-year-old girl who presented with fever, encephalopathy, and seizure. Neuromyotonia or other dyskinesia was not present. Conclusions: Eight anti-NMDA receptor antibody positive patients and one CASPR2 positive patient were identified from the screening of six anti-neuronal antibodies in pediatric patients suspected with autoimmune encephalitis. Developmental regression specifically for language skills was suggested as one of the atypical clinical features in infants and toddler onset anti-NMDA receptor antibody positive patients. PMID:25625089

Kim, Soo Yeon; Choi, Sun Ah; Ryu, Hye Won; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Chae, Jong-Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung; Lee, Soon-Tae; Chu, Kon; Lee, Sang Kun

2014-01-01

251

Monoclonal antibodies: versatile platforms for cancer immunotherapy  

Microsoft Academic Search

Antibodies are important therapeutic agents for cancer. Recently, it has become clear that antibodies possess several clinically relevant mechanisms of action. Many clinically useful antibodies can manipulate tumour-related signalling. In addition, antibodies exhibit various immunomodulatory properties and, by directly activating or inhibiting molecules of the immune system, antibodies can promote the induction of antitumour immune responses. These immunomodulatory properties can

Rishi Surana; Shangzi Wang; Louis M. Weiner

2010-01-01

252

Anti-flavin antibodies.  

PubMed Central

Antibodies were elicited to FAD by using the hapten N-6-(6-aminohexyl)-FAD conjugated to the immunogenic carrier protein bovine serum albumin. Cross-reactivity was determined by Ouchterlony double-diffusion analysis with N-6-(6-aminohexyl)-FAD coupled to rabbit serum albumin. Anti-FAD IgG was partially purified by (NH4)2SO4 precipitation followed by DEAE-cellulose/CM-cellulose and bovine serum albumin-agarose chromatography. The partially purified anti-FAD IgG fraction failed to inhibit the catalytic activities of the flavin-containing enzymes nitrate reductase, xanthine oxidase and succinate dehydrogenase, whereas enzyme activity could be inhibited by addition of antibodies elicited against the native proteins. However, the partially purified anti-FAD IgG fraction could be used as a highly sensitive and specific probe to detect proteins containing only covalently bound flavin, such as succinate dehydrogenase, p-cresol methylhydroxylase and monoamine oxidase, by immuno-blotting techniques. Detection limits were estimated to be of the order of femtomolar concentrations of FAD with increased sensitivity for the 8 alpha-N(3)-histidyl linkage compared with 8 alpha-O-tyrosyl substitution. Images Fig. 1. Fig. 3. Fig. 4. Fig. 5. Fig. 6. PMID:3109386

Barber, M J; Eichler, D C; Solomonson, L P; Ackrell, B A

1987-01-01

253

Antibody remodeling: a general solution to the design of a metal-coordination site in an antibody binding pocket.  

PubMed Central

To develop a general approach to designing cofactor-binding sites for catalytic antibodies, we characterized structural patterns in the binding sites of antibodies and zinc enzymes. Superposition of eight sets of antibody light- and heavy-chain variable domains identified structurally conserved sites within the sequence-variable complementarity determining regions. The pattern for catalytic zinc sites included two ligands close in sequence, a sequence-distant ligand, and a main-chain hydrogen bond joining two ligands. In both the light- and heavy-chain variable domains, the stereochemistry of five structurally conserved sites general to all known antibody structures matched that of the zinc ligands of carbonic anhydrase: three residues on two hydrogen-bonded antiparallel beta-strands. For one such general site, an antibody model replacing residue 34 on the first complementarity determining region of the light chain (L1) and residues 89 and 91 on the third complementarity determining region of the light chain (L3) with histidine ligands formed a zinc-binding site with an open coordination position at the bottom of the antibody binding pocket. For the anti-fluorescein antibody 4-4-20, this L1-L3 site placed the zinc ion about 4 A from the bound fluorescein, an indicator for metal binding. This predicted zinc-binding mutant was created in the single-chain variable domain construct, expressed, and found by fluorescence quenching to bind metal ion with an affinity constant of 10(6) M-1. Thus, our template-based multisite design proved successful for remodeling an antibody to contain a cofactor-binding site, without requiring further mutagenesis and screening. Combination of a specific light or heavy chain containing a catalytic metal site with a library of complementary chains raised to potential substrates or transition state analogs should greatly improve the production of catalytic antibodies with desired activities and specificities. Images PMID:2395868

Roberts, V A; Iverson, B L; Iverson, S A; Benkovic, S J; Lerner, R A; Getzoff, E D; Tainer, J A

1990-01-01

254

Catumaxomab: a bispecific trifunctional antibody.  

PubMed

The trifunctional bispecific monoclonal antibody catumaxomab has two binding specificities directed at epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells such as dendritic cells, macrophages and natural killer cells. The trifunctional approach thus leads to unrestricted but specific killing of epithelial tumor cells by major histocompatibility complex without the need for preactivation or external costimulation. The tumor-associated antigen EpCAM is strongly expressed in carcinomas of various origins including colon, rectum, ovarian, gastric, esophagus, lung, pancreas, breast and head and neck. Expression of EpCAM is often associated with an unfavorable prognosis in patients with breast cancer. Catumaxomab has been approved in Europe for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive epithelial tumors when standard therapy is not available or is no longer feasible. Basic preclinical and clinical findings with different routes of catumaxomab administration in various indications are summarized and discussed in this review. PMID:19927225

Sebastian, M; Kuemmel, A; Schmidt, M; Schmittel, A

2009-08-01

255

[Therapeutic monoclonal antibodies in oncology].  

PubMed

Advances in bioengineering have lead to the possibility to conduct large scale production of monoclonal antibodies (MoAB) and to reduce progressively the murine component from 30% (chimeric MoAB) to 5% (humanized MoAB) to 0% (human MoAB). Three types of extracellular components are targeted in solid tumours: (1) Growth factors with transmembrane tyrosine kinase receptors either of tumour cells (IGF1) or endothelial cells (Bevacizumab). Bevacizumab has activity additive to that of chemotherapy in advanced colorectal, non squamous lung, ovarian, metastatic breast cancers and glioblastomas; (2) Extracellular domain of those transmembrane receptors: EGFR in colorectal cancer if no activating of KRAS with cetuximab and panitumumab, head and neck carcinomas with radiotherapy, and probably squamous lung cancers. Anti-ERBB2 MoAb are now a constitutive part of therapy of ERBB2 positive breast cancers at any stage; (3) Differentiation cluster regulating relationship ot tumour and stromal cells and in particular immunologic effectors. This is the case of anti-CTLA4 MoAB ipilimumab which activates and amplifies immunological cytotoxic response against melanoma with improved survival. These activities are achieved to the expense of class, target related toxicity conditioned by expression of the target on normal cells and or mechanism of action (immunological toxicity with ipilimumab). Of note a synergistic or additive activity with valid treatment regimens of targeted cancers and now targeted small molecules. PMID:22863361

Bouzid, K; Bedairia, N; Marty, M

2012-08-01

256

Seropositivity of Dengue Antibodies during Pregnancy  

PubMed Central

Purpose. Malaysia a dengue endemic country with dengue infections in pregnancy on the rise. The present study was aimed at determining dengue seroprevalence (IgG or IgM) during pregnancy and its neonatal transmission in dengue seropositive women. Methods. Maternal with paired cord blood samples were tested for dengue antibodies (IgG and IgM) using an enzyme-linked immunosorbent assay (ELISA). Maternal age, parity, occupation, ethnic group, and gestational age were recorded. Data on neonatal Apgar score and admissions to the Neonatal Intensive Care Unit (NICU) were analyzed. Results. Out of 358 women recruited, about 128 (35.8%) patients were seropositive. Twelve patients (3.4%) had recent infections (IgM positive) and another 116 women (32.4%) were with past infections (IgG positive). All babies born to seropositive mothers had positive IgG paired cord blood; however, no IgM seropositivity was observed. All neonates had good Apgar scores and did not require NICU admission. Conclusion. In this study, 35.8% pregnant women were found to be dengue seropositive. However, transplacental transfer of IgG antibodies had no detrimental effect on the neonatal outcomes. PMID:25587564

Mohamed Ismail, Nor Azlin; Wan Abd Rahim, Wan Elly Rushima; Salleh, Sharifah Azura; Neoh, Hui-Min; Jamal, Rahman; Jamil, Muhammad Abdul

2014-01-01

257

Inflammatory myopathies associated with anti-mitochondrial antibodies.  

PubMed

Anti-mitochondrial antibodies, the characteristic markers of primary biliary cirrhosis, have been detected in most patients with this disease. However, the prevalence of these antibodies in inflammatory myopathies and their clinical and histopathological significance has not been determined. Sera from 212 consecutive patients with inflammatory myopathies were screened for anti-mitochondrial antibodies by enzyme-linked immunosorbent assay. The clinical and histopathological features of anti-mitochondrial antibody-positive patients were analysed and statistically compared with those of anti-mitochondrial antibody-negative patients. Twenty-four patients positive for anti-mitochondrial antibodies (seven patients with and 17 patients without primary biliary cirrhosis) were identified (11.3%). Thirteen patients had a clinically chronic disease course of >12 months before their diagnosis at hospitals. Six of these 13 patients (four asymptomatic patients with increased creatine kinase levels and two patients with arrhythmia) had not been aware of muscle weakness, but all 13 patients had muscle atrophy at initial presentation. As complications, eight patients had cardiac involvement including arrhythmias (five patients with supraventricular tachycardia; two with ventricular tachycardia; and one patient with atrioventricular block), six patients had moderately decreased ejection fraction and six patients had decreased vital capacity, two of whom required respiratory support. Regarding muscle histopathological findings, in addition to inflammation, 13 patients had chronic myopathic changes and six had granulomatous lesions. Statistical analysis showed that the clinical features of a chronic disease course, cardiac involvement and muscle atrophy, and the histopathological features of chronic myopathic changes and granulomatous inflammation, were significantly more frequently observed in patients with anti-mitochondrial antibody-positive inflammatory myopathy than in patients who were negative for anti-mitochondrial antibodies. Except for cardiac involvement, which is more frequently observed in patients with primary biliary cirrhosis, no significant differences in clinical or histopathological features were found between patients with or without primary biliary cirrhosis. Our study revealed that inflammatory myopathies associated with anti-mitochondrial antibodies were frequently found in patients with the clinical features of a chronic disease course, muscle atrophy and cardiopulmonary involvement, and the characteristic histopathological feature of granulomatous inflammation. Our study suggests that inflammatory myopathies associated with anti-mitochondrial antibodies form a characteristic subgroup. PMID:22561642

Maeda, Meiko Hashimoto; Tsuji, Shoji; Shimizu, Jun

2012-06-01

258

Tubulin assembly probed with antibodies to synthetic peptides.  

PubMed

Antibodies to synthetic peptides from the alpha and beta-tubulin sequences were employed to study zones of this protein active in microtubule assembly. In purified calf brain tubulin, six short sequences, selected according to their hydrophilicity and conservation, were found to be accessible to their affinity-purified immunoglobulin G (IgG) antibodies, in a competition radioimmunoassay performed under non-assembly native conditions. This indicated that the six sequences are exposed on the surface of the tubulin alpha beta heterodimer. IgG antibodies to the alpha(430-443) and beta(412-431) sequences perturbed substoichiometrically the assembly of purified tubulin, inducing microtubule bundling and the formation of opened up structures. These positions, which are close to the C termini, were accessible to the anti-peptide antibodies in taxol-induced microtubules, Zn2(+)-induced tubulin sheets, Mg2(+)-induced tubulin rings and in PtK2 cell microtubules. This, together with the comparison of the sizes and gross shapes of the antibody probes and microtubules, suggested that these sequences might be located at the protruding parts of the protofilaments. Antibodies to positions alpha(155-168) did not react with microtubules, while the equivalent zone beta(153-165) was accessible. The alpha(214-226) and beta(241-256) sequences were antigenically occluded in the taxol microtubules, Zn2(+)-induced sheets and Mg2(+)-induced ring arrays, as well as in native microtubules from PtK2 cells, though they became reactive by fixation. This result strongly suggested that these two zones are close to tubulin-tubulin contact sites. A working model is proposed in which the positions alpha(214-226) and beta(241-256) are close to the axial contacts between heterodimers, which lead to protofilament formation, while the positions alpha(241-256) and beta(214-226) are suggested to be related to the alpha-beta binding interface within the heterodimer. PMID:1695248

Arévalo, M A; Nieto, J M; Andreu, D; Andreu, J M

1990-07-01

259

Recent advances in the development of anti-HER2 antibodies and antibody-drug conjugates.  

PubMed

Human epidermal growth factor receptor 2 (HER2)-targeted therapies have revolutionized the treatment of HER2-positive breast cancer, both in the metastatic and early stage settings. While trastuzumab and lapatinib had been the mainstays of treatment in combination with chemotherapy, innate and acquired resistance to these therapies occur. More recently, two additional HER2-directed therapies have been approved for HER2-positive breast cancer. Pertuzumab is a humanized monoclonal antibody that binds to the extracellular portion of the receptor on a domain distinct from the binding site of trastuzumab. The addition of pertuzumab to trastuzumab results in synergistic tumor cell inhibition and has been shown to significantly improve clinical outcomes for patients with HER2-positive metastatic breast cancer (MBC) compared to trastuzumab plus chemotherapy alone. In addition, ado-trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate linking trastuzumab with the cytotoxic maytansinoid, DM1, is an effective treatment for HER2-positive breast cancer that has progressed on other HER2-directed therapies. Both pertuzumab and T-DM1 are relatively well tolerated. This review presents the mechanisms of action as well as phase I, II and III clinical data describing the safety and efficacy of pertuzumab and T-DM1 for HER2-positive breast cancer. PMID:25568875

Wong, Deborah J L; Hurvitz, Sara A

2014-12-01

260

Recent advances in the development of anti-HER2 antibodies and antibody-drug conjugates  

PubMed Central

Human epidermal growth factor receptor 2 (HER2)-targeted therapies have revolutionized the treatment of HER2-positive breast cancer, both in the metastatic and early stage settings. While trastuzumab and lapatinib had been the mainstays of treatment in combination with chemotherapy, innate and acquired resistance to these therapies occur. More recently, two additional HER2-directed therapies have been approved for HER2-positive breast cancer. Pertuzumab is a humanized monoclonal antibody that binds to the extracellular portion of the receptor on a domain distinct from the binding site of trastuzumab. The addition of pertuzumab to trastuzumab results in synergistic tumor cell inhibition and has been shown to significantly improve clinical outcomes for patients with HER2-positive metastatic breast cancer (MBC) compared to trastuzumab plus chemotherapy alone. In addition, ado-trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate linking trastuzumab with the cytotoxic maytansinoid, DM1, is an effective treatment for HER2-positive breast cancer that has progressed on other HER2-directed therapies. Both pertuzumab and T-DM1 are relatively well tolerated. This review presents the mechanisms of action as well as phase I, II and III clinical data describing the safety and efficacy of pertuzumab and T-DM1 for HER2-positive breast cancer. PMID:25568875

Wong, Deborah J.L.

2014-01-01

261

A revival of bispecific antibodies  

Microsoft Academic Search

Bispecific antibodies usually do not occur in nature but are constructed by recombinant DNA or cell-fusion technologies. Most are designed to recruit cytotoxic effector cells of the immune system effectively against pathogenic target cells. This complex task explains why, after more than 15 years of extensive research, many different formats of bispecific antibodies have been developed but only a few

Peter Kufer; Ralf Lutterbüse; Patrick A. Baeuerle

2004-01-01

262

Chemical generation of bispecific antibodies  

PubMed Central

Bispecific antibodies (BsAbs) are regarded as promising therapeutic agents due to their ability to simultaneously bind two different antigens. Several bispecific modalities have been developed, but their utility is limited due to problems with stability and manufacturing complexity. Here we report a versatile technology, based on a scaffold antibody and pharmacophore peptide heterodimers, that enables rapid generation and chemical optimization of bispecific antibodies, which are termed bispecific CovX-Bodies. Two different peptides are joined together using a branched azetidinone linker and fused to the scaffold antibody under mild conditions in a site-specific manner. Whereas the pharmacophores are responsible for functional activities, the antibody scaffold imparts long half-life and Ig-like distribution. The pharmacophores can be chemically optimized or replaced with other pharmacophores to generate optimized or unique bispecific antibodies. As a prototype, we developed a bispecific antibody that binds both vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang2) simultaneously, inhibits their function, shows efficacy in tumor xenograft studies, and greatly augments the antitumor effects of standard chemotherapy. This unique antiangiogenic bispecific antibody is in phase-1 clinical trials. PMID:21149738

Doppalapudi, Venkata R.; Huang, Jie; Liu, Dingguo; Jin, Ping; Liu, Bin; Li, Lingna; Desharnais, Joel; Hagen, Crystal; Levin, Nancy J.; Shields, Michael J.; Parish, Michelle; Murphy, Robert E.; Del Rosario, Joselyn; Oates, Bryan D.; Lai, Jing-Yu; Matin, Marla J.; Ainekulu, Zemeda; Bhat, Abhijit; Bradshaw, Curt W.; Woodnutt, Gary; Lerner, Richard A.; Lappe, Rodney W.

2010-01-01

263

Bispecific antibodies for cancer therapy  

PubMed Central

With 23 approvals in the US and other countries and four approvals outside US, antibodies are now widely recognized as therapeutic molecules. The therapeutic and commercial successes met by rituximab, trastuzumab, cetuximab and other mAbs have inspired antibody engineers to improve the efficacy of these molecules. Consequently, a new wave of antibodies with engineered Fc leading to much higher effector functions such as antibody-dependent cell-mediated cytotoxicity or complement-dependent cytotoxicity is being evaluated in the clinic, and several approvals are expected soon. In addition, research on a different class of antibody therapeutics, bispecific antibodies, has recently led to outstanding clinical results, and the first approval of the bispecific antibody catumaxomab, a T cell retargeting agent that was approved in the European Union in April 2009. This review describes the most recent advances and clinical study results in the field of bispecific antibodies, a new class of molecules that might outshine conventional mAbs as cancer immunotherapeutics in a near future. PMID:20073127

Baty, Daniel

2009-01-01

264

Detection of antibody to encephalomyocarditis virus in mummified or stillborn pigs.  

PubMed

Fetal sera or thoracic fluids of the abnormal fetuses from different swine farms were tested for the presence of antibody to encephalomyocarditis (EMC) virus. Sera of swine fetuses infected experimentally with EMC virus were also tested. High antibody titers ranging 1:128-4096 were detected in both field and experimental samples. Detection of the positive antibody was associated with clinical herd history of increased mummification, stillbirth and neonatal death. The results suggest that EMC virus may be a natural cause of swine reproductive failure and fetal infection can be diagnosed by detecting specific EMC virus antibody in either fetal sera or thoracic fluids. PMID:2839129

Joo, H S; Kim, H S; Leman, A D

1988-01-01

265

Endogenous Antibodies for Tumor Detection  

PubMed Central

The study of cancer immunology has provided diagnostic and therapeutic instruments through serum autoantibody biomarkers and exogenous monoclonal antibodies. While some endogenous antibodies are found within or surrounding transformed tissue, the extent to which this exists has not been entirely characterized. We find that in transgenic and xenograft mouse models of cancer, endogenous gamma immunoglobulin (IgG) is present at higher concentration in malignantly transformed organs compared to non-transformed organs in the same mouse or organs of cognate wild-type mice. The enrichment of endogenous antibodies within the malignant tissue provides a potential means of identifying and tracking malignant cells in vivo as they mutate and diversify. Exploiting these antibodies for diagnostic and therapeutic purposes is possible through the use of agents that bind endogenous antibodies. PMID:24875800

Rich, Barrie S.; Honeyman, Joshua N.; Darcy, David G.; Smith, Peter T.; Williams, Andrew R.; Lim, Irene Isabel P.; Johnson, Linda K.; Gönen, Mithat; Simon, Joel S.; LaQuaglia, Michael P.; Simon, Sanford M.

2014-01-01

266

Prevalence of Herpes Simplex Virus Antibodies in Dental Students.  

ERIC Educational Resources Information Center

A study of 125 sophomore preclinical dental students found that these young professionals, because of having a low prevalence of herpes simplex virus (HSV) antibodies, are at risk for acquiring a primary HSV infection when treating HSV positive patients and should take precautions to avoid virus transmission. (MSE)

Rodu, Brad; And Others

1992-01-01

267

Micromechanical antibody sensor  

DOEpatents

A sensor apparatus is provided using a microcantilevered spring element having a coating of a detector molecule such as an antibody or antigen. A sample containing a target molecule or substrate is provided to the coating. The spring element bends in response to the stress induced by the binding which occurs between the detector and target molecules. Deflections of the cantilever are detected by a variety of detection techniques. The microcantilever may be approximately 1 to 200 .mu.m long, approximately 1 to 50 .mu.m wide, and approximately 0.3 to 3.0 .mu.m thick. A sensitivity for detection of deflections is in the range of 0.01 nanometers.

Thundat, Thomas G. (Knoxville, TN); Jacobson, K. Bruce (Oak Ridge, TN); Doktycz, Mitchel J. (Knoxville, TN); Kennel, Stephen J. (Oak Ridge, TN); Warmack, Robert J. (Knoxville, TN)

2001-01-01

268

Red cell antibody problems in 1000 liver transplants  

PubMed Central

Liver transplant patients frequently require large amounts of blood. The frequency and nature of their red cell (RBC) antibody problems were examined. Records were reviewed in 496 adults and 286 children undergoing 1000 consecutive transplants. Twenty-two percent of adults and 14 percent of children had RBC alloantibodies. Antibodies of potential clinical significance were found before transplant in 6.3 percent of adults and 1.0 percent of children; despite immunosuppression, they appeared 1 to 5 weeks after transplant in an additional 7.5 and 5.2 percent respectively. These antibodies probably represented secondary immune responses. Of 58 transplant patients with prior potentially significant antibodies, 8 required 7 to 110 units of antigen-untyped blood after 8 to 28 units of antigen-negative blood; of these patients, one had subsequent hemolysis. Positive direct antiglobulin tests in 24 percent of adults and 10 percent of children were most often thought to be due to nonspecific adsorption of IgG. Anti-recipient ABO antibodies developed in 22 of 60 (37%) evaluable ABO-unmatched grafts; 13 cases had associated hemolysis. In all, 36 percent of adults and 20 percent of children had diverse RBC antibody problems. Resolution of these problems is an important part of the laboratory support necessary for a liver transplantation program. PMID:2660334

Ramsey, G.; Cornell, F. W.; Hahn, L. F.; Larson, P.; Issitt, L. B.; Starzl, T. E.

2010-01-01

269

Induction of immunity to a human tumor marker by in vivo administration of anti-idiotypic antibodies in mice.  

PubMed Central

Anti-idiotypic antibodies are described that were raised against murine monoclonal antibody 8.2, an antibody specific for a human melanoma-associated cell surface marker called p97. The 8.2 idiotopes recognized by this anti-idiotypic antiserum are binding site-associated and are shared by other monoclonal anti-p97 antibodies with the same specificity as antibody 8.2. Mice immunized with the anti-idiotype demonstrate delayed-type hypersensitivity reactions when challenged with melanoma (p97-positive) tumor cells. PMID:6609369

Nepom, G T; Nelson, K A; Holbeck, S L; Hellström, I; Hellström, K E

1984-01-01

270

Prevalence of antibodies to Leishmania infantum and Trypanosoma cruzi in wild canids from South Carolina.  

PubMed

Wild canids are reservoir hosts for Leishmania infantum and Trypanosoma cruzi. The present study examined the prevalence of antibodies to these zoonotic parasites in a population of wild canids from a nonagricultural setting in South Carolina. Sera from 26 gray foxes (Urocyon cinereoargenteus) and 2 coyotes (Canis latrans) were examined for antibodies to L. infantum and T. cruzi using the indirect immunofluorescent antibody test and commercially available parasite-specific immunochromatigraphic strip assays. Antibodies to L. infantum were not detected by either assay in gray foxes or coyotes. Two (8%) of 26 gray foxes were positive in both the T. cruzi immunofluorescent antibody and strip assays. Antibodies to T. cruzi were not detected in coyotes. Results from this study indicate that wild canids are exposed to T. cruzi, but not L. infantum. in this geographic region. PMID:17918387

Rosypal, Alexa C; Tidwell, Richard R; Lindsay, David S

2007-08-01

271

Application of phage display to high throughput antibody generation and characterization  

PubMed Central

We have created a high quality phage display library containing over 1010 human antibodies and describe its use in the generation of antibodies on an unprecedented scale. We have selected, screened and sequenced over 38,000 recombinant antibodies to 292 antigens, yielding over 7,200 unique clones. 4,400 antibodies were characterized by specificity testing and detailed sequence analysis and the data/clones are available online. Sensitive detection was demonstrated in a bead based flow cytometry assay. Furthermore, positive staining by immunohistochemistry on tissue microarrays was found for 37% (143/381) of antibodies. Thus, we have demonstrated the potential of and illuminated the issues associated with genome-wide monoclonal antibody generation. PMID:18047641

Schofield, Darren J; Pope, Anthony R; Clementel, Veronica; Buckell, Jenny; Chapple, Susan DJ; Clarke, Kay F; Conquer, Jennie S; Crofts, Anna M; Crowther, Sandra RE; Dyson, Michael R; Flack, Gillian; Griffin, Gareth J; Hooks, Yvette; Howat, William J; Kolb-Kokocinski, Anja; Kunze, Susan; Martin, Cecile D; Maslen, Gareth L; Mitchell, Joanne N; O'Sullivan, Maureen; Perera, Rajika L; Roake, Wendy; Shadbolt, S Paul; Vincent, Karen J; Warford, Anthony; Wilson, Wendy E; Xie, Jane; Young, Joyce L; McCafferty, John

2007-01-01

272

Antibody-mediated inhibition of ricin toxin retrograde transport.  

PubMed

Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin's binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. IMPORTANCE Ricin is the prototypic member of the AB family of medically important plant and bacterial toxins that includes cholera and Shiga toxins. Ricin is also a category B biothreat agent. Despite ongoing efforts to develop vaccines and antibody-based therapeutics against ricin, very little is known about the mechanisms by which antibodies neutralize this toxin. In general, it is thought that antibodies simply prevent toxins from attaching to cell surface receptors or promote their clearance through Fc receptor (FcR)-mediated uptake. In this report, however, we describe a neutralizing monoclonal antibody (MAb) against ricin's binding subunit (RTB) that not only associates with ricin after the toxin has bound to the cell's surface but actually enhances toxin uptake into host cells. Following endocytosis, the antibody-toxin complexes are then routed for degradation. The results of this study are important because they reveal a previously unappreciated role for B-subunit-specific antibodies in intracellular neutralization of ricin toxin. PMID:24713323

Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J

2014-01-01

273

Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5.  

PubMed Central

New Zealand black x New Zealand white (NZB/W) F1 mice spontaneously develop an autoimmune syndrome with notable similarities to human systemic lupus erythematosus. Female NZB/WF1 mice produce high titers of antinuclear antibodies and invariably succumb to severe glomerulonephritis by 12 months of age. Although the development of the immune-complex nephritis is accompanied by abundant local and systemic complement activation, the role of proinflammatory complement components in disease progression has not been established. In this study we have examined the contribution of activated terminal complement proteins to the pathogenesis of the lupus-like autoimmune disease. Female NZB/W F1 mice were treated with a monoclonal antibody (mAb) specific for the C5 component of complement that blocks the cleavage of C5 and thus prevents the generation of the potent proinflammatory factors C5a and C5b-9. Continuous therapy with anti-C5 mAb for 6 months resulted in significant amelioration of the course of glomerulonephritis and in markedly increased survival. These findings demonstrate an important role for the terminal complement cascade in the progression of renal disease in NZB/W F1 mice, and suggest that mAb-mediated C5 inhibition may be a useful approach to the therapy of immune-complex glomerulonephritis in humans. Images Fig. 3 Fig. 5 PMID:8710910

Wang, Y; Hu, Q; Madri, J A; Rollins, S A; Chodera, A; Matis, L A

1996-01-01

274

Fully Human Antagonistic Antibodies against CCR4 Potently Inhibit Cell Signaling and Chemotaxis  

PubMed Central

Background CC chemokine receptor 4 (CCR4) represents a potentially important target for cancer immunotherapy due to its expression on tumor infiltrating immune cells including regulatory T cells (Tregs) and on tumor cells in several cancer types and its role in metastasis. Methodology Using phage display, human antibody library, affinity maturation and a cell-based antibody selection strategy, the antibody variants against human CCR4 were generated. These antibodies effectively competed with ligand binding, were able to block ligand-induced signaling and cell migration, and demonstrated efficient killing of CCR4-positive tumor cells via ADCC and phagocytosis. In a mouse model of human T-cell lymphoma, significant survival benefit was demonstrated for animals treated with the newly selected anti-CCR4 antibodies. Significance For the first time, successful generation of anti- G-protein coupled chemokine receptor (GPCR) antibodies using human non-immune library and phage display on GPCR-expressing cells was demonstrated. The generated anti-CCR4 antibodies possess a dual mode of action (inhibition of ligand-induced signaling and antibody-directed tumor cell killing). The data demonstrate that the anti-tumor activity in vivo is mediated, at least in part, through Fc-receptor dependent effector mechanisms, such as ADCC and phagocytosis. Anti-CC chemokine receptor 4 antibodies inhibiting receptor signaling have potential as immunomodulatory antibodies for cancer. PMID:25080123

Géraudie, Solène; Scheffler, Ulrike; Griep, Remko A.; Reiersen, Herald; Duncan, Alexander R.; Kiprijanov, Sergej M.

2014-01-01

275

Offered: Offered: Position(s): Position(s)  

E-print Network

profitability and identifying variances Experience ?General Accounting and Financial Analysis experience in this position is responsible for supporting the Finance group in the monthly closings, variance analysis, sales analysis and providing assistance to division Financial Analysts. ?Support Finance group in General

New Hampshire, University of

276

Golgi Positioning  

PubMed Central

The Golgi apparatus in mammalian cells is positioned near the centrosome-based microtubule-organizing center (Fig. 1). Secretory cargo moves inward in membrane carriers for delivery to Golgi membranes in which it is processed and packaged for transport outward to the plasma membrane. Cytoplasmic dynein motor proteins (herein termed dynein) primarily mediate inward cargo carrier movement and Golgi positioning. These motors move along microtubules toward microtubule minus-ends embedded in centrosomes. Centripetal motility is controlled by a host of regulators whose precise functions remain to be determined. Significantly, a specific Golgi receptor for dynein has not been identified. This has impaired progress toward elucidation of membrane-motor-microtubule attachment in the periphery and, after inward movement, recycling of the motor for another round. Pericentrosomal positioning of the Golgi apparatus is dynamic. It is regulated during critical cellular processes such as mitosis, differentiation, cell polarization, and cell migration. Positioning is also important as it aligns the Golgi along an axis of cell polarity. In certain cell types, this promotes secretion directed to the proximal plasma membrane domain thereby maintaining specializations critical for diverse processes including wound healing, immunological synapse formation, and axon determination. PMID:21504874

Yadav, Smita; Linstedt, Adam D.

2011-01-01

277

Restricted diversity of antigen binding residues of antibodies revealed by computational alanine scanning of 227 antibody-antigen complexes.  

PubMed

Antibody molecules are able to recognize any antigen with high affinity and specificity. To get insight into the molecular diversity at the source of this functional diversity, we compiled and analyzed a non-redundant aligned collection of 227 structures of antibody-antigen complexes. Free energy of binding of all the residue side chains was quantified by computational alanine scanning, allowing the first large-scale quantitative description of antibody paratopes. This demonstrated that as few as 8 residues among 30 key positions are sufficient to explain 80% of the binding free energy in most complexes. At these positions, the residue distribution is not only different from that of other surface residues but also dependent on the role played by the side chain in the interaction, residues participating in the binding energy being mainly aromatic residues, and Gly or Ser otherwise. To question the generality of these binding characteristics, we isolated an antibody fragment by phage display using a biased synthetic repertoire with only two diversified complementarity-determining regions and solved its structure in complex with its antigen. Despite this restricted diversity, the structure demonstrated that all complementarity-determining regions were involved in the interaction with the antigen and that the rules derived from the natural antibody repertoire apply to this synthetic binder, thus demonstrating the robustness and universality of our results. PMID:25174334

Robin, Gautier; Sato, Yoshiteru; Desplancq, Dominique; Rochel, Natacha; Weiss, Etienne; Martineau, Pierre

2014-11-11

278

Antibody responses to deamidated gliadin peptide show high specificity and parallel antibodies to tissue transglutaminase in developing coeliac disease  

PubMed Central

Coeliac disease (CD) is an enteropathy induced in genetically susceptible individuals by gluten components, gliadin, hordein and secalin, polypeptides present in cereals such as wheat, barley and rye, respectively. Although the disease starts as intolerance to gliadins, antibodies to tissue transglutaminase (tTG) in the gut epithelium are characteristic of the disease. Whereas serum autoantibodies against tTG (tTGA) are highly specific for CD, antibodies to gliadin are less informative as they can also be detected in other enteropathies, and even in healthy individuals. However, it was shown recently that antibodies to certain gliadin peptides occur with high specificity in CD patient sera. We developed a solid phase lanthanide-based immunofluorometric assay for simultaneous detection of serum IgA and IgG antibodies to a synthetic peptide derived from gamma gliadin of wheat comprising amino acids 86–103. Three glutamine residues of this native 18-mer peptide were replaced by glutamic acids and the peptide was biotinylated. Sera from 87 individuals who had undergone duodenal biopsy and were diagnosed with CD and from 81 healthy individuals were analysed for the presence of both IgA and IgG anti-gliadin peptide antibodies. The performance of the peptide AGA assay was excellent, showing a specificity and sensitivity of 90% and 92% for IgA, and 98% and 75% for IgG, respectively. The corresponding values for conventional anti-gliadin antibody (AGA) enzyme-linked immunosorbent assay (ELISA) tests were 72% specificity and 87% sensitivity for IgA, and 64% specificity and 78% sensitivity for IgG. In a prospective study, almost all the tTGA-positive sera drawn from children who later developed CD were also positive for gliadin peptide antibodies. PMID:17803713

Ankelo, M; Kleimola, V; Simell, S; Simell, O; Knip, M; Jokisalo, E; Tarkia, M; Westerlund, A; He, Q; Viander, M; Ilonen, J; Hinkkanen, A E

2007-01-01

279

Anti-Gliadin Antibodies Identify Celiac Patients Overlooked by Tissue Transglutaminase Antibodies  

PubMed Central

For patients with suspected celiac disease, the American Gastroenterological Association recommends initial screening with anti-tissue transglutaminase antibody (tTG) and confirmation testing with small bowel biopsy. However, at Tripler Army Medical Center we routinely screen patients with both tTG and anti-gliadin antibodies (AGA) in combination. The purpose of this study was to evaluate whether this dual screening method adds to the evaluation of patients with suspected celiac disease or results in more false-positive results than tTG screening alone. A retrospective chart review of all tTG and AGA screening serologies at Tripler Army Medical Center between September 2008 and March 2012 was performed. For patients with positive serologic testing, small bowel biopsy results or reasoning for deferring biopsy were investigated. tTG was found to have a higher positive predictive value for celiac disease than AGA, however AGA identified 5 patients (19% of biopsy confirmed celiac disease) that had a negative tTG and would not have been identified by tTG screening alone. Using AGA in combination with tTG should be considered if the goal of screening is to identify all patients with celiac disease, with the understanding that this strategy will generate more false positive tests and result in additional patients undergoing small bowel biopsy. PMID:24052912

Mulder, Christopher J; Laczek, Jeffrey T

2013-01-01

280

POSTER PRESENTATION Open Access Genetic markers in clinical subtypes of juvenile  

E-print Network

cri- teria as antinuclear antibodies (ANA), age of beginning or uveitis. Our objective was to look developed an uveitis, especially when AAN are positive (14 associated with oligoarticular form). 38 were to be associated with the risk of uveitis, but this association is not significant. We did not find association

Paris-Sud XI, Université de

281

Acute eosinophilic ascites: An unusual form of an unusual case.  

PubMed

Eosinophilic gastroenteritis (EGE) is an uncommon disease characterised by eosinophilic infiltration in the gastrointestinal tract. EGE may involve more than one layer of the gastrointestinal tract. Clinical features depend on the layer and location which is involved. We report an unusual case of eosinophilic ascites associated with antinuclear antibody positivity, which is an unusual variety of serosal form of EGE. PMID:25315240

Kodan, Parul; Shetty, Meenakshi A; Pavan, Mr; Kariappa, Ahalya; Mahabala, Chakrapani

2015-01-01

282

Anti–JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy  

PubMed Central

Objective The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti–JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients. Methods The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody–positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated. Results Anti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody–positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p?antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time. Interpretation Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody–positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted. Ann Neurol 2014;76:802–812 PMID:25273271

Plavina, Tatiana; Subramanyam, Meena; Bloomgren, Gary; Richman, Sandra; Pace, Amy; Lee, Sophia; Schlain, Brian; Campagnolo, Denise; Belachew, Shibeshih; Ticho, Barry

2014-01-01

283

Antineutrophil cytoplasmic antibody-associated vasculitis with oculomotor nerve palsy.  

PubMed

We report a patient with antineutrophil cytoplasmic antibody-associated vasculitis with oculomotor nerve palsy. The patient presented with a high fever, diplopia, blepharoptosis and impairment of ocular movement of the left eye except for lateral gaze. Multiple erythematous and livedoid lesions were observed on the forehead, both cheeks and both legs. Laboratory examination showed positive results for myeloperoxidase antineutrophil cytoplasmic antibodies. Skin biopsy revealed leucocytoclastic vasculitis of the small arteries in the lower dermis. The patient was successfully treated with systemic corticosteroids. PMID:19187297

Seishima, M; Mizutani, Y; Shibuya, Y; Arakawa, C

2009-03-01

284

Schmallenberg virus antibody persistence in adult cattle after natural infection and decay of maternal antibodies in calves  

PubMed Central

Background Schmallenberg virus (SBV) has swept through the major part of Europe in the period 2011–2013. A vaccine against SBV has been developed and may be a possible preventive instrument against infection. Presently, there is no data available to refute the assumption that natural SBV infection results in long-term immunity. In that respect, it is of interest to know how long (protecting) virus-neutralizing antibodies are present in naturally infected animals. New-born calves acquire passive immunity from their dams by ingestion and absorption of antibodies present in colostrum, which can block the production of serum antibodies when vaccine is administered to calves with maternally derived antibodies. In that respect, it is useful to know how long it takes for maternal antibodies against SBV to disappear in young animals born from infected dams. Results Longitudinal whole-herd serological monitoring using virus neutralization test (VNT) indicated that 80% of adult dairy cows still had measurable antibodies against SBV at least 24 months after the estimated introduction of the virus into the herd. Median 2Log VNT titer of the adult dairy cows (?1 year) dropped from 8.6 to 5.6 in a period of 17 months. Median 2Log VNT maternal antibodies titers of calves sampled within 30 days after birth was 8. Calves lost their maternally-derived antibodies after 5–6 months. There was a definite positive relationship between the VNT titer of the dam and the VNT titer of the corresponding calf (age ? 30 days) of dam-calf combinations sampled on the same day: the higher the VNT titer of the dam, the higher the VNT titer (maternal antibodies) of the calf. Conclusions Our field data support the assumption that natural SBV infection in adult cows results in persistence of specific antibodies for at least two years. Based on the observed decay of maternally-derived antibodies in calves, it is presumed safe to vaccinate calves against SBV at an age of approximately 6 months. PMID:24885026

2014-01-01

285

Anti-phospholipase A2 receptor antibody in idiopathic membranous nephropathy: A report from Iranian population  

PubMed Central

Background: Idiopathic Membranous Nephropathy (iMN) is the most common cause of nephrotic syndrome in adults. Approximately one third of patients with iMN progress to end-stage renal disease. Anti-phospholipase A2-receptor (anti-PLA2R) antibodies are present in patients with iMN and appear to play a role in the pathogenesis of iMN. Objectives: In this study, we explored the prevalence of anti-PLA2R antibodies in a cohort of patients with iMN in Iran. We also sought to determine circulating levels of anti-secretory PLA2 (anti-sPLA2) antibodies in those with anti-PLA2R antibodies. Patients and Methods: Using an indirect immunofluorescence assay, we measured anti-PLA2R antibodies in a group of patients with iMN in Iran. The serum levels of anti-sPLA2 antibodies were also measured in those with positive results for anti-PLA2R antibodies. Results: We studied 23 patients with iMN (M/F 12/11, 34±9.8 year), two patients with secondary MN and five patients  with the nephrotic syndrome of other causes.Anti-PLA2R antibodies were detected in 17/23 (74%) of patients with iMN, but not in those with secondary MN or other forms of primary glomerular diseases. We found no correlation between anti-PLA2R antibody titer and the degree of proteinuria. We found high titers of anti-sPLA2 antibodies in a subset of patients with high levels of anti-PLA2R antibodies. Conclusions: Anti-PLA2R antibodies are specific for iMN. Proteinuria may also reflect glomerular structural damage rather than immunological activity of the disease. The preliminary idea of any presumptive role of anti-sPLA2antibodies in iMN needs further  investigation. PMID:24475456

Ardalan, MohammadReza; Ghafari, Ali; Hamzavi, Fatemeh; Nasri, Hamid; Baradaran, Behrooz; Majidi, Jafar; Nikbin, Behrooz

2013-01-01

286

FcalphaRI (CD89) as a novel trigger molecule for bispecific antibody therapy.  

PubMed

Promising results from clinical trials with unconjugated antibodies stimulated renewed interest in immune effector mechanisms of monoclonal antibodies (MoAbs). We investigated the potential of IgA as antibody isotype for cell- or complement-mediated tumor cell lysis and assessed the potential of its myeloid Fc receptor, FcalphaRI (CD89), as trigger molecule for bispecific antibody (BsAb)-mediated immunotherapy. Comparing hapten-directed antibodies of human IgA2 with IgG1 or IgG3 isotypes, we found all three to mediate effective killing of sensitized tumor target cells in whole blood assays. Analysis of effector mechanisms showed IgG-mediated lysis to be predominantly complement-dependent, whereas IgA-dependent killing was primarily effector cell-mediated. A comparison of effector cell populations in antibody-dependent cell-mediated cytotoxicity (ADCC) showed neutrophils to be most important for IgA-dependent tumor cell killing, involving FcalphaRI as shown with Fc receptor blocking antibodies. Reverse ADCC experiments against target cells sensitized with Fc receptor antibodies, or assays with FcalphaRI-directed bispecific antibodies confirmed FcalphaRI as effective trigger molecule in polymorphonuclear neutrophil (PMN)-mediated lysis. During granulocyte colony-stimulating factor (G-CSF ) therapy, (FcalphaRI x HER-2/neu) bispecific antibodies induced enhanced killing of HER-2/neu positive SK-BR-3 breast cancer cells in whole blood assays. This enhanced cytotoxicity was paralleled by increased PMN counts, which lead to higher effector to target cell ratios in G-CSF-primed blood. Furthermore, bispecific antibodies, directed to FcalphaRI and Candida albicans, enhanced neutrophils' phagocytosis of fungi. In summary, these results identify IgA as an effective antibody isotype for immunotherapy, working primarily via FcalphaRI on neutrophils. They suggest FcalphaRI-directed bispecific antibodies and G-CSF to be an attractive combination for malignant or infectious diseases. PMID:9373259

Valerius, T; Stockmeyer, B; van Spriel, A B; Graziano, R F; van den Herik-Oudijk, I E; Repp, R; Deo, Y M; Lund, J; Kalden, J R; Gramatzki, M; van de Winkel, J G

1997-12-01

287

Detection of Antibodies against Aspergillus fumigatus: Comparison between Double Immunodiffusion, ELISA and Immunoblot Analysis  

Microsoft Academic Search

The performance of ELISA to detect IgG and IgM antibodies to Aspergillus fumigatus has been evaluated in strongly precipitin-positive, weakly precipitin-positive and precipitin-negative patient sera, with immunoblot analysis as the confirmatory test. All strongly precipitin-positive sera contained increased IgG titers and showed clearly positive immunoblot patterns. Most of the weakly precipitin-positive sera contained ELISA titers within the normal range established

J. Brouwer

1988-01-01

288

Seroprevalence of bovine viral diarrhea virus neutralizing antibodies in finisher hogs in Ontario swine herds and targeted diagnostic testing of 2 suspect herds  

PubMed Central

A pilot study was initiated to determine the seroprevalence of bovine viral diarrhea virus (BVDV) neutralizing antibodies in finisher hogs in Ontario swine herds, including 2 swine herds with clinical syndromes suspicious of BVDV. No herds were positive for BVDV antibodies by virus neutralization. The 2 swine herds with clinical disease suggestive of pestivirus infection were also negative for antibodies to BVDV in indirect fluorescent antibody assays. Prevalence of BVDV in Ontario swine farms is negligible. PMID:22654141

O’Sullivan, Terri; Friendship, Robert; Carman, Susy; Pearl, David L.; McEwen, Beverly; Dewey, Catherine

2011-01-01

289

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease  

PubMed Central

Anti-Mycobacterium tuberculosis IgG antibodies may aid in the diagnosis of active M. tuberculosis disease. We studied whether anti-M. tuberculosis IgG antibodies are elevated in active M. tuberculosis disease and assessed factors contributing to false-positive and -negative results. A retrospective study of 2,150 individuals tested by the QuantiFERON-TB Gold In-Tube (QFT-GIT) assay was conducted at the University of Utah, ARUP Laboratories, November 2008 to December 2010. All samples were tested with the InBios Active TbDetect antituberculosis (anti-TB) IgG antibody assay. Of 1,044 patients with a positive QFT-GIT, 59 (5.7%) were positive for M. tuberculosis antibodies. Fourteen of 1,106 (1.3%) with a negative or indeterminate QFT-GIT were positive for M. tuberculosis antibodies. M. tuberculosis antibody tests were positive in 61.5% with confirmed active M. tuberculosis disease and other mycobacterial infections. Over half of the false-negative M. tuberculosis antibody tests occurred in patients ?90 years of age. False positives were seen in 12.9% of autoimmune patients. The odds ratio of being positive by the QFT-GIT and the InBios TB IgG assay increased with confirmed M. tuberculosis disease or highly suspected M. tuberculosis disease and was 86.7 (95% confidence interval [CI], 34.4 to 218.5) in these two groups compared to patients negative by both tests. Although anti-M. tuberculosis antibodies can be detected in patients with active M. tuberculosis disease, caution should be used with patients where immunoglobulin levels may be decreased or patients with autoantibodies. PMID:22301692

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

290

Bispecific Antibodies from Hybrid Hybridoma  

Microsoft Academic Search

\\u000a Hybrid hybridomas (also termed quadromas or tetradomas) are man-made cell lines that secrete bispecific antibodies (bsAb)\\u000a with two different specificities being able to crosslink two distinct molecules. Such antibodies do not occur in nature and\\u000a have been originally developed to improve immunohistochemical staining procedures and immunoassays (Milstein and Cuello 1983;\\u000a Suresh et al. 1986). Interestingly, the fusion of two immunoglobulin-producing

Gerhard Moldenhauer

291

Bispecific Antibodies and Gene Therapy  

Microsoft Academic Search

\\u000a Gene therapy is the transfer of therapeutic genes, via gene transfer vectors, into patients for therapeutic purposes. Different\\u000a gene therapy strategies are being pursued, including long-term gene correction of monogenetic diseases, eradication of tumor\\u000a cells in cancer patients, or genetic vaccination for infectious diseases. Bispecific antibodies and gene therapy are connected\\u000a in two ways. First, bispecific antibodies are tools of

Dirk M. Nettelbeck

292

Antiphospholipid antibodies: specificity and pathophysiology.  

PubMed

Antiphospholipid antibodies are autoantibodies that can be detected in plasma or serum with phospholipid-dependent coagulation tests or solid-phase immunoassays. The presence of these autoantibodies is strongly associated with an increased risk for arterial and venous thrombosis, recurrent fetal loss and thrombocytopenia. This paradoxical association of the in vitro prolongation of clotting assays and in vivo thrombosis has stimulated the search for the real antigen to which the autoantibodies are directed. A large number of potential pathological mechanisms have been proposed, and although disturbance of a certain metabolic pathway by the antibodies can explain a thrombotic tendency in one patient, no general pathological mechanism explaining thrombosis in the whole patient population has been found. This suggests that the antiphospholipid antibodies are a heterogeneous group of autoantibodies and is supported by the recent observations that antiphospholipid antibodies are not directed against phospholipids alone but against a combination of phospholipids and phospholipid-binding proteins. Both the phospholipid and the protein are part of the antigen. For the detection of antiphospholipids in an ELISA set-up, beta 2-glycoprotein I is the protein cofactor. In the coagulation tests, beta 2-glycoprotein, as well as prothrombin, can act as cofactor. However, the presence of these two proteins as a part of the epitope of the antiphospholipid antibodies does not explain the thrombotic tendency in the patient group. We have found that more physiologically relevant cofactors such as protein C and protein S, for which it is known that a partial deficiency is correlated with a thrombotic tendency, can also act as cofactors for the binding of antiphospholipid antibodies. It is concluded that antiphospholipid antibodies are a heterogeneous group of autoantibodies with varying affinity for different protein-phospholipid complexes and that inhibition of the biological activity of the protein part of the complex determines the pathological capacity of the antibodies. PMID:8025348

de Groot, P G; Oosting, J D; Derksen, R H

1993-09-01

293

Monoclonal antibodies to the human mammary gland  

Microsoft Academic Search

Mouse monoclonal antibodies have been raised to the human milk fat globule membrane. The distribution of the antigens detected by four of the antibodies has been examined in formalin-fixed, paraffin-embedded human tissues by light microscopic immunocytochemistry. The four antibodies stain lactating breast and normal resting breast. Two exclusively stain the luminal membranes of breast epithelial cells. A third antibody stains

C. S. Foster; P. A. W. Edwards; E. A. Dinsdale; A. M. Neville

1982-01-01

294

Antibodies to watch in 2015.  

PubMed

The commercial pipeline of recombinant antibody therapeutics is robust and dynamic. As of early December 2014, a total of 6 such products (vedolizumab, siltuximab, ramucirumab, pembrolizumab, nivolumab, blinatumomab) were granted first marketing approvals in 2014. As discussed in this perspective on antibodies in late-stage development, the outlook for additional approvals, potentially still in 2014 and certainly in 2015, is excellent as marketing applications for 7 antibody therapeutics (secukinumab, evolocumab, mepolizumab, dinutuximab, nivolumab, blinatumomab, necitumumab) are undergoing a first regulatory review in the EU or US. Of the 39 novel mAbs currently in Phase 3 studies, a marketing application for one (alirocumab) may be submitted in late 2014, and marketing application submissions for at least 4 (reslizumab, ixekizumab, ocrelizumab, obiltoxaximab) are expected in 2015. Other 'antibodies to watch' are those in Phase 3 studies with estimated primary completion dates in late 2014 or 2015, which includes 13 for non-cancer indications (brodalumab, bimagrumab, bococizumab, MABp1, gevokizumab, dupilumab, sirukumab, sarilumab, tildrakizumab, guselkumab, epratuzumab, combination of actoxumab + bezlotoxumab, romosozumab) and 2 (racotumomab and clivatuzumab tetraxetan) undergoing evaluation as treatments for cancer. In addition to the novel antibody therapeutics mentioned, biosimilar infliximab and biosimilar trastuzumab are 'antibodies to watch' in 2015 because of their potential for entry into the US market and regulatory review, respectively. PMID:25484055

Reichert, Janice M

2015-01-01

295

Antibodies to watch in 2014  

PubMed Central

Since 2010, mAbs has documented the biopharmaceutical industry’s progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the “Antibodies to watch” series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration’s Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

Reichert, Janice M

2014-01-01

296

Antibodies to watch in 2014.  

PubMed

Since 2010, mAbs has documented the biopharmaceutical industry's progress in transitioning antibody therapeutics to first Phase 3 clinical studies and regulatory review, and its success at gaining first marketing approvals for antibody-based products. This installment of the "Antibodies to watch" series outlines events anticipated to occur between December 2013 and the end of 2014, including first regulatory actions on marketing applications for vedolizumab, siltuximab, and ramucirumab, as well as the Fc fusion proteins Factor IX-Fc and Factor VIII-Fc; and the submission of first marketing applications for up to five therapeutics (secukinumab, ch14.18, onartuzumab, necitumumab, gevokizumab). Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab). Five antibodies with US Food and Drug Administration's Breakthrough Therapy designation (obinutuzumab, ofatumumab, lambrolizumab, bimagrumab, daratumumab) are also discussed. PMID:24284914

Reichert, Janice M

2014-01-01

297

Avian Diagnostic and Therapeutic Antibodies  

SciTech Connect

A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

Bradley, David Sherman [UND SMHS] [UND SMHS

2012-12-31

298

Detecting Lyme disease using antibody-functionalized carbon nanotubes  

NASA Astrophysics Data System (ADS)

We combine antibodies for Lyme flagellar protein with carbon nanotube transistors to create an electronic sensor capable of definitive detection of Lyme disease. Over 35,000 cases of Lyme disease are reported in the United States each year, of which more than 23 percent are originally misdiagnosed. Rational design of the coupling of the biological system to the electronic system gives us a flexible sensor platform which we can apply to several biological systems. By coupling these antibodies to carbon nanotubes in particular, we allow for fast, sensitive, highly selective, electronic detection. Unlike antibody or biomarker detection, bacterial protein detection leads to positive identification of both early and late stage bacterial infections, and is easily expandable to environmental monitoring.

Dailey, Jennifer; Lerner, Mitchell; Goldsmith, Brett; Brisson, Dustin; Johnson, A. T. Charlie

2011-03-01

299

Positioning apparatus  

DOEpatents

An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

Vogel, Max A. (Kennewick, WA); Alter, Paul (Richland, WA)

1986-01-01

300

Satellite positioning  

NASA Astrophysics Data System (ADS)

The Fifth International Geodetic Symposium on Satellite Positioning was held in Las Cruces, N.Mex., March 13-17, 1989. It was cosponsored by the Defense Mapping Agency and the National Geodetic Survey of the National Oceanic and Atmospheric Administration. More than 385 geodesists, engineers, scientists, surveyors, instrument manufacturers, and managers from 32 countries attended the symposium.The keynote address and 96 papers including 9 invited papers and 10 poster papers were presented in the 5-day meeting. In addition, there were three well-attended workshops with lively technical discussions. The invited guest presentations at the symposium luncheon and banquet provided very useful and interesting information.

Stein, William L.; Kumar, Muneendra

301

Positioning apparatus  

DOEpatents

An apparatus is provided for precisely adjusting the position of an article relative to a beam emerging from a neutron source disposed in a housing. The apparatus includes a support pivotably mounted on a movable base plate and freely suspended therefrom. The support is gravity biased toward the housing and carries an article holder movable in a first direction longitudinally of the axis of said beam and normally urged into engagement against said housing. Means are provided for moving the base plate in two directions to effect movement of the suspended holder in two mutually perpendicular directions, respectively, normal to the axis of the beam.

Vogel, M.A.; Alter, P.

1983-07-07

302

Antibody-targeted radiation cancer therapy  

Microsoft Academic Search

Several monoclonal antibodies are now approved for cancer therapy, such as rituximab, an anti-CD20 monoclonal antibody for the treatment of B-cell non-Hodgkin's lymphoma. Such 'naked' antibodies can recruit the body's immune effector mechanisms to kill cells expressing the target of the antibody. In recent years, the linking of radionuclides to antibodies to either augment inherent activity or to exploit the

Diane E. Milenic; Erik D. Brady; Martin W. Brechbiel

2004-01-01

303

Anti-voltage-gated potassium channel Kv1.4 antibodies in myasthenia gravis.  

PubMed

Myasthenia gravis (MG) is an autoimmune disease characterized by skeletal muscle weakness mainly caused by acetylcholine receptor antibodies. MG can be divided into generalized and ocular, and into early-onset (<50 years of age) and late-onset (?50 years of age). Anti-Kv1.4 antibodies targeting ?-subunits (Kv1.4) of the voltage-gated potassium K(+) channel occurs frequently among patients with severe MG, accounting for 18% of a Japanese MG population. The aim of this study was to characterize the clinical features and serological associations of anti-Kv1.4 antibodies in a Caucasian MG population with mild and localized MG. Serum samples from 129 Caucasian MG patients with mainly ocular symptoms were tested for the presence of anti-Kv1.4 antibodies and compared to clinical and serological parameters. There were 22 (17%) anti-Kv1.4 antibody-positive patients, most of them women with late-onset MG, and all of them with mild MG. This contrasts to the Japanese anti-Kv1.4 antibody-positive patients who suffered from severe MG with bulbar symptoms, myasthenic crisis, thymoma, myocarditis and prolonged QT time on electrocardiography, despite equal anti-Kv1.4 antibody occurrence in both populations. No other clinical or serological parameters influenced anti-Kv1.4 antibody occurrence. PMID:22167224

Romi, Fredrik; Suzuki, Shigeaki; Suzuki, Norihiro; Petzold, Axel; Plant, Gordon T; Gilhus, Nils Erik

2012-07-01

304

Enzyme Immunoassays for Measurement of Cytomegalovirus Immunoglobulin M Antibody  

PubMed Central

The diagnosis of congenital cytomegalovirus (CMV) infection is often accomplished by the detection of circulating antibody directed against CMV. We devised a method for measuring CMV-specific immunoglobulin M (IgM) based on the isolation of IgM antibody by reaction with a solid phase coated with antihuman IgM. The determination of IgM antibody specific for CMV was accomplished by the subsequent addition of CMV or control antigen and enzyme-labeled CMV antibody (solid phase-IgM method). We compared the sensitivity and specificity of this method with those of a conventional form of solid-phase enzyme immunoassay in which CMV antigen is bound to the solid phase (solid phase-antigen method). Both assay systems were capable of detecting CMV-specific IgM antibody in the sera of 10 babies with documented CMV infection and in those of the mothers of 4 of these babies. The solid phase-IgM method yielded negative results in all 66 sera available from babies who did not have congenital CMV infection. On the other hand, the solid phase-antigen system yielded false-positive results in 12 (18%) of these sera. In addition, the solid phase-antigen system yielded false-positive results in 8 of 12 sera obtained from patients with demonstrable rheumatoid factor. However, the solid phase-IgM system yielded negative results for the rheumatoid sera, provided that appropriate control reactions were performed. The solid phase-IgM system is thus a specific and sensitive method for the determination of CMV IgM antibody. PMID:6270191

Yolken, Robert H.; Leister, Flora J.

1981-01-01

305

Chlamydia pneumoniae antibodies and inflammatory reaction in patients with ischemic heart disease.  

PubMed

We studied the relationship between Chlamydia pneumoniae antibodies, C-reactive protein (CRP) and interleukine 8 (IL-8) in 87 patients with ischemic heart disease: 29 patients with acute myocardial infarction, 18 patients with unstable angina pectoris and 40 patients with stable effort angina. We determined in all patients IgG and IgA antibodies to Chlamydia pneumoniae, CRP and IL-8. Species specific antibodies to Chlamydia pneumoniae (IgG and IgA) were detected by indirect ELISA technique (Savyon Diagnostics Ltd, Israel). Interleukine-8 measured by a commercially available ELISA kit (CLB, Amsterdam, The Netherlands). CRP was determined by radial immunodiffusion (Mancini). The IgG antibodies were present in 25 patients (29%), the greatest percentage being noted in patients with unstable angina pectoris (50%). The IgA antibodies were present, as a sign of chronic Chlamydia pneumoniae infection, in 56% of the patients with IgG antibodies. CRP was positive in 52% of the 25 patients with positive IgG antibodies, but in only 34% of the 62 patients without IgG antibodies (p < 0.01). IL-8 was positive in 12% of the patients with IgG antibodies, and in 21% of the patients without IgG antibodies but the difference is not significant (p > 0.05). It is concluded that there is a relationship between the presence of the Chlamydia pneumoniae infection and inflammatory reaction in patients with ischemic heart disease, but the neutrophils are not implied in this process. PMID:15529571

Zdrenghea, D; Bodizs, G; Talo?, C; Stanciu, A; Ro?u, R; Timi?, D; Alua?, D

306

Benign positional vertigo  

MedlinePLUS

Vertigo - positional; Benign paroxysmal positional vertigo; BPPV: dizziness- positional ... Benign positional vertigo is also called benign paroxysmal positional ... ear has fluid-filled tubes called semicircular canals. When ...

307

Evolution of an HIV glycan–dependent broadly neutralizing antibody epitope through immune escape  

PubMed Central

Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful1-3, a minority of individuals naturally develop these antibodies after many years of infection4-7. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1–infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly underrepresented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes. PMID:23086475

Moore, Penny L; Gray, Elin S; Wibmer, C Kurt; Bhiman, Jinal N; Nonyane, Molati; Sheward, Daniel J; Hermanus, Tandile; Bajimaya, Shringkhala; Tumba, Nancy L; Abrahams, Melissa-Rose; Lambson, Bronwen E; Ranchobe, Nthabeleng; Ping, Lihua; Ngandu, Nobubelo; Karim, Quarraisha Abdool; Karim, Salim S Abdool; Swanstrom, Ronald I; Seaman, Michael S; Williamson, Carolyn; Morris, Lynn

2012-01-01

308

Evolution of an HIV glycan-dependent broadly neutralizing antibody epitope through immune escape.  

PubMed

Neutralizing antibodies are likely to play a crucial part in a preventative HIV-1 vaccine. Although efforts to elicit broadly cross-neutralizing (BCN) antibodies by vaccination have been unsuccessful, a minority of individuals naturally develop these antibodies after many years of infection. How such antibodies arise, and the role of viral evolution in shaping these responses, is unknown. Here we show, in two HIV-1-infected individuals who developed BCN antibodies targeting the glycan at Asn332 on the gp120 envelope, that this glycan was absent on the initial infecting virus. However, this BCN epitope evolved within 6 months, through immune escape from earlier strain-specific antibodies that resulted in a shift of a glycan to position 332. Both viruses that lacked the glycan at amino acid 332 were resistant to the Asn332-dependent BCN monoclonal antibody PGT128 (ref. 8), whereas escaped variants that acquired this glycan were sensitive. Analysis of large sequence and neutralization data sets showed the 332 glycan to be significantly under-represented in transmitted subtype C viruses compared to chronic viruses, with the absence of this glycan corresponding with resistance to PGT128. These findings highlight the dynamic interplay between early antibodies and viral escape in driving the evolution of conserved BCN antibody epitopes. PMID:23086475

Moore, Penny L; Gray, Elin S; Wibmer, C Kurt; Bhiman, Jinal N; Nonyane, Molati; Sheward, Daniel J; Hermanus, Tandile; Bajimaya, Shringkhala; Tumba, Nancy L; Abrahams, Melissa-Rose; Lambson, Bronwen E; Ranchobe, Nthabeleng; Ping, Lihua; Ngandu, Nobubelo; Abdool Karim, Quarraisha; Abdool Karim, Salim S; Swanstrom, Ronald I; Seaman, Michael S; Williamson, Carolyn; Morris, Lynn

2012-11-01

309

Increased Prevalence of Transglutaminase 6 Antibodies in Sera From Schizophrenia Patients  

PubMed Central

Gluten can cause extraintestinal manifestations with or without gastrointestinal symptoms and elevated antitissue transglutaminase 2 (tTG2) autoantibodies. Organ-specific gluten reaction involves immune response toward other transglutaminase (TG) isoforms including tTG3 (expressed in the skin, leading to dermatitis herpetiformis) and tTG6 (expressed in the brain, causing gluten ataxia). This analysis focuses on tTG6 antibodies, which have never been studied before in schizophrenia (SZ) and its relationships to tTG2 and to antigliadin antibodies. We previously showed an increased prevalence of tTG2 antibodies in gluten sensitive SZ patients compared with healthy controls (HC) that was not paralleled by an increased prevalence of antiendomysial antibody. To elucidate this discrepancy, we examined those tTG2 positive SZ patients for the presence of tTG6 antibody. We also searched for tTG6 antibodies in our sample of antigliadin (AGA) positive and AGA and tTG2 negative SZ patients. Seventy-four tTG2 positive SZ patients were compared with 148 age and gender-matched HC. Of the 74 tTG2 positive SZ patients, 16 were positive for tTG6 IgA for a prevalence of 22%. Only 4 HC were positive for tTG6 IgA for a prevalence of 2.7%. Among the AGA positive SZ patients, the prevalence of tTG6 IgA was 21.3% while 13.1% of the AGA and tTG2 negative SZ patients were positive for tTG6 IgA. The HC had a prevalence of 6%. Our results indicate a higher prevalence of tTG6 antibodies in SZ that may represent a biomarker useful to identify SZ patients who would benefit from a gluten-free diet. PMID:22516148

Cascella, Nicola G.; Santora, Debby; Gregory, Patricia; Kelly, Deanna L.; Fasano, Alessio; Eaton, William W.

2013-01-01

310

Monoclonal antibodies to type X collagen. Biosynthetic studies using an antibody to the amino-terminal domain.  

PubMed

Monoclonal antibodies to chick type X collagen have been used to study the structure, biosynthesis, and location of type X in cartilage. The antibodies were produced by injecting purified type X collagen into female SJL/J mice and then fusing their spleen cells with Sp2/0 myeloma cells. Hybridoma culture supernatants were screened for antibodies to type X collagen by enzyme-linked immunosorbent assay and Western blots. Positive supernatants did not cross-react with other collagen types (I, II, IX, XI) or with fibronectin. Three monoclonal antibodies were chosen for further characterization. Two of them (1A6 and 6F6) recognize a pepsin-sensitive domain of type X collagen. Rotary shadowing showed that 1A6 and 6F6 both recognize the same end of type X, probably the aminoterminal non-triple helical domain. Amino acid sequencing of the intact protein and of the epitope-containing peptide confirmed that the antibody recognition sites for 1A6 and 6F6 are within the amino-terminal domain. Monoclonal antibody 2B3 reacts with the pepsinized (45 kDa) and weakly with the nonpepsinized (59 kDa) forms of type X collagen. The monoclonal antibodies were used for immunolocalization of type X in hypertrophic chondrocytes and reacted only with tissue samples from areas undergoing endochondral ossification, e.g. growth plate and fracture callus. Antibody 6F6, when coupled to Sepharose, selectively binds to type X collagen from cell and organ cultures. In a pulse-chase experiment, no processing of the 59-kDa form of type X could be detected. Two components with molecular masses of approximately 70 and 85 kDa, arising from a disulfide-bonded aggregate, were synthesized by both the permanent and calcifying cartilage organ cultures but did not react with the antibody, suggesting that these proteins are not related to type X. In summary, the pulse-chase results and the immune precipitation with monoclonal antibody 6F6 did not detect biosynthetic precursors larger than 59 kDa or proteolytically processed forms of type X. PMID:2826450

Summers, T A; Irwin, M H; Mayne, R; Balian, G

1988-01-01

311

Preferential adsorption of cationic anti-DNA antibodies with immobilized polyanionic compounds, dextran sulfate.  

PubMed

It has been shown that cationic anti-DNA antibodies have nephritogenic potential in murine models of lupus nephritis. More recently, we have reported that there is a close relationship between the presence of circulating cationic anti-DNA antibodies and the development of lupus nephritis in humans, and that the cationic anti-DNA antibodies bind to heparan sulfate, a major glycosaminoglycan in glomerular basement membrane, much better than neutral anti-DNA antibodies. This suggests that cationic anti-DNA antibodies of the IgG class may be responsible for development of nephritis in vivo in patients with systemic lupus erythematosus. In this study, we first studied reactivity of anti-DNA antibodies with a panel of glycosaminoglycans in vitro using ELISA methods, and found that anti-DNA antibodies cross-react with dextran sulfate, hyaluronic acid and chrondroitin sulfate. The reactivity and selectivity of dextran sulfate with anti-DNA antibodies was confirmed by in vitro immunoadsorption of the patient's sera with dextran sulfate-fixed column; incubation of auto-antibody-positive sera with dextran sulfate cellulose column removed anti-DNA, but not anti-RNP, anti-Sm, anti-SSA and anti-SSB antibodies from the sera in vitro. Of note is that dextran sulfate cellulose column absorbed exclusively, if not all, cationic anti-DNA antibodies in their sera. Nonspecific binding of total immunoglobulins as well as total proteins to the column was marginal. It has been suggested that cationic anti-DNA antibodies in sera of patients with refractory lupus nephritis could be efficiently removed by apheresis using dextran sulfate column. PMID:7772700

Suzuki, N; Otuka, I; Harada, T; Mizushima, Y; Sakane, T

1994-01-01

312

Antibody-Mediated Inhibition of Ricin Toxin Retrograde Transport  

PubMed Central

ABSTRACT Ricin is a member of the ubiquitous family of plant and bacterial AB toxins that gain entry into the cytosol of host cells through receptor-mediated endocytosis and retrograde traffic through the trans-Golgi network (TGN) and endoplasmic reticulum (ER). While a few ricin toxin-specific neutralizing monoclonal antibodies (MAbs) have been identified, the mechanisms by which these antibodies prevent toxin-induced cell death are largely unknown. Using immunofluorescence confocal microscopy and a TGN-specific sulfation assay, we demonstrate that 24B11, a MAb against ricin’s binding subunit (RTB), associates with ricin in solution or when prebound to cell surfaces and then markedly enhances toxin uptake into host cells. Following endocytosis, however, toxin-antibody complexes failed to reach the TGN; instead, they were shunted to Rab7-positive late endosomes and LAMP-1-positive lysosomes. Monovalent 24B11 Fab fragments also interfered with toxin retrograde transport, indicating that neither cross-linking of membrane glycoproteins/glycolipids nor the recently identified intracellular Fc receptor is required to derail ricin en route to the TGN. Identification of the mechanism(s) by which antibodies like 24B11 neutralize ricin will advance our fundamental understanding of protein trafficking in mammalian cells and may lead to the discovery of new classes of toxin inhibitors and therapeutics for biodefense and emerging infectious diseases. PMID:24713323

Yermakova, Anastasiya; Klokk, Tove Irene; Cole, Richard; Sandvig, Kirsten; Mantis, Nicholas J.

2014-01-01

313

Mechanism of an antibody-catalysed allylic isomerization.  

PubMed Central

The catalytic antibody 4B2, which was generated against a substituted amidine 1, catalyses the allylic isomerization of beta, gamma-unsaturated ketones with an acceleration factor (k(cat)/k(uncat)) of 1.5x10(3). On the basis of the 'bait and switch' strategy, it was reasoned that the positively charged hapten could elicit, by charge complementarity, an acidic residue (Asp or Glu) in the antibody-binding site in the right position to catalyse this proton transfer reaction. The pH dependence curve of k(cat)/K(m) shows a bell-shaped feature with an optimum at approx. pH 4.5. By cloning and sequencing the light and heavy chains of the 4B2 antibody, we confirmed the presence of several Asp and Glu residues in the complementarity-determining region loops. The antibody catalyses the alpha-proton exchange on the same substrates, demonstrating the involvement of a dienol intermediate in the reaction mechanism. Kinetic studies with (2)H-NMR provide evidence that alpha-proton abstraction is stereospecific. Whether the process involves one or two acid/base residues in this simple proton transfer or whether it is a concerted mechanism is discussed. PMID:10698695

Gonçalves, O; Dintinger, T; Lebreton, J; Blanchard, D; Tellier, C

2000-01-01

314

Clinical Analysis of Thyroglobulin Antibody and Thyroid Peroxidase Antibody and their Association with Vitiligo  

PubMed Central

Background: Recently, the abnormal presence of thyroglobulin antibody (TG-Ab) and thyroid peroxidase antibody (TPO-Ab) has been reported in vitiligo patients, but presence of TG-Ab and TPO-Ab in patients of different ages and gender, and its association with vitiligo and thyroid autoimmunity has rarely been reported. The aim of our research was to determine whether vitiligo was associated with thyroid autoimmunity and figure out its relationship with age and gender. Materials and Methods: We analyzed TG-Ab, TPO-Ab in age and gender matched 87 vitiligo patients and 90 healthy controls, the patients of vitiligo who were positive for the presence of TG-Ab and TPO-Ab were followed up to confirm autoimmune thyroid disease subsequently. Results: Results showed that the frequencies of TG-Ab (23.0%, 20/87) positivity and TPO-AB (24.1%, 21/87) in vitiligo patients were significantly higher than that in healthy controls (P < 0.05). Moreover, The positivity for of TG-Ab and TPO-Ab was higher in 11-20-year age group and 21-40-year age group than that in age matched healthy controls. We found female patients with vitiligo had higher positive frequencies of TG-Ab and TPO-Ab than healthy female controls. (34.1% vs. 8.8% and 34.1% vs. 11.1%, P = 0.000 and P = 0.011). When 20 patients with TG-Ab and TPO-Ab positivity were followed up for three monthes, 14 of them (70%) were diagnosed as having autoimmune thyroid disease compared with age-matched healthy controls (16.7%, ?2 = 5.4, P = 0.02). Conclusion: TG-Ab and TPO-Ab are likely to be found in female teenagers with vitiligo, and are relevant with respect to subsequent development autoimmune thyroid disease. PMID:25071254

Yang, Yifen; Huang, Gan; Yan, Xiang; Qing, Zhiju

2014-01-01

315

Autoantibody potential of cancer therapeutic monoclonal antibodies.  

PubMed

We and others have reported that multiple autoantibodies are unmasked in human polyclonal antibody preparations after exposure to physiological oxidizing agents (hemin) or electromotive force. We now have asked if oxidation unmasks autoantibody reactivities in monoclonal antibodies (mAb). To do this, we have studied 9 FDA approved mAb used therapeutically, including 4 chimeric, 4 humanized and 1 chemically modified chimeric Fab that were exposed to the physiological oxidizing agent hemin at 36 degrees C for 20 hr. These mAb were studied for autoantibody activity to phospholipids and DNA before and after oxidation with hemin and found to develop autoantibody activities after oxidation, while retaining their original specificity as measured by mAb anti-glycophorin A binding of erythrocytes, CD 19 binding to B lymphocytes and anti-HLA-A29 binding to A29-positive lymphocytes. The finding that certain mAb have the potential to unmask autoantibody activities as a consequence of exposure to physiological redox reactions in vitro gives pause to our present understanding of the immunological basis of tolerance and concern for potential autoimmune side effects in patients receiving mAb for diagnosis or treatment. PMID:19904753

McIntyre, John A; Faulk, And W Page

2010-07-15

316

Production of recombinant antibodies using bacteriophages  

PubMed Central

Recombinant antibody fragments such as Fab, scFv, diabodies, triabodies, single domain antibodies and minibodies have recently emerged as potential alternatives to monoclonal antibodies, which can be engineered using phage display technology. These antibodies match the strengths of conventionally produced monoclonal antibodies and offer advantages for the development of immunodiagnostic kits and assays. These fragments not only retain the specificity of the whole monoclonal antibodies but also easy to express and produce in prokaryotic expression system. Further, these antibody fragments are genetically stable, less expensive, easy to modify in response to viral mutations and safer than monoclonal antibodies for use in diagnostic and therapeutic applications. This review describes the potential of antibody fragments generated using phage display and their use as diagnostic reagents. PMID:24883194

Shukra, A. M.; Sridevi, N. V.; Dev Chandran

2014-01-01

317

Uses of monoclonal antibody 8H9  

DOEpatents

This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

Cheung, Nai-Kong V.

2013-04-09

318

Differentiation of cytomegalovirus antigens by their reactivity with various classes of human antibodies in the indirect fluorescent antibody test.  

PubMed Central

Human sera containing immunoglobulin G (IgG), IgA, and IgM antibodies were tested by immunofluorescence for reactivity with cytomegalovirus-infected cell cultures and with early antigens of cytomegalovirus produced by treating the infected cultures with either bromodeoxyuridine or cytosine arabinoside. IgG antibody but not IgM antibody reacted with early antigens produced in bromodeoxyuridine-treated infected cultures. This observation on a small sample of sera suggested that a positive IgM reaction with an infected, nontreated culture and a negative reaction with a bromodeoxyuridine-treated infected culture may indicate a positive specific IgM reaction for cytomegalovirus, even in the presence of IgM rhematoid factor. The hyothesis requires further testing. The different classes of antibody did not all react or did not react to the same extent with early antigens produced in infected cells blocked with cytosine arabinoside or bromodeoxyuridine. This observation indicates that different antigens were being produced as a result of the two treatments. Images PMID:6243674

Riggs, J L; Cremer, N E

1980-01-01

319

Prevalence of Antibody to Toxic Shock Syndrome Toxin-1 in Burn Patients  

PubMed Central

Background Burn wounds lack normal barriers that protect against pathogenic bacteria, and burn patients are easily colonized and infected by Staphylococcus aureus. Toxic shock syndrome (TSS) is a rare but fatal disease caused by S. aureus. A lack of detectable antibodies to TSS toxin-1 (TSST-1) in serum indicates susceptibility to TSS. Methods A total of 207 patients (169 men and 38 women; median age, 42.5 yr) admitted to a burn center in Korea were enrolled in this study. The serum antibody titer to TSST-1 was measured by sandwich ELISA. S. aureus isolates from the patients' nasal swab culture were tested for TSST-1 toxin production by PCR-based detection of the TSST-1 toxin gene. Results One hundred seventy-four (84.1%) patients showed positive results for antibody against TSST-1. All patients aged ?61 yr (n=28) and <26 months (n=7) were positive for the anti-TSST-1 antibody. S. aureus was isolated from 70 patients (33.8%), and 58.6% of the isolates were methicillin resistant. Seventeen patients were colonized with TSST-1-producing S. aureus. The antibody positivity in these 17 carriers was 88.2%, and the positivity in the non-carriers was 83.7%. Conclusions Most burn patients had antibody to TSST-1, and nasal colonization with TSST-1-producing S. aureus was associated with positive titers of anti-TSST-1 antibody. Additionally, patients with negative titers of anti-TSST-1 antibody might be susceptible to TSS. PMID:25553286

Park, Ji-Young

2015-01-01

320

Epigenetics of the antibody response.  

PubMed

Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia. PMID:23643790

Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

2013-09-01

321

Molecular-specific urokinase antibodies  

NASA Technical Reports Server (NTRS)

Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

2009-01-01

322

Antibodies to watch in 2013  

PubMed Central

The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing evaluation in late-stage studies is 30. Recently announced study results for farletuzumab, naptumomab estafenatox, and tabalumab indicate that clinical endpoints were not met in some Phase 3 studies of these product candidates. PMID:23727858

Reichert, Janice M

2013-01-01

323

Intestinal biopsy is not always required to diagnose celiac disease: a retrospective analysis of combined antibody tests  

PubMed Central

Background The objective of this study was to compare celiac disease (CD)– specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of CD. Methods This retrospective study included sera from 149 CD patients and 119 controls, all with intestinal biopsy. All samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium. Results Tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Positive (76% vs. 93%) and negative (72% vs. 83%) predictive values were also higher for dpgli than for ngli. Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P < 0.00001). A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00. Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01. Conclusion Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium permitted diagnosis or exclusion of CD without intestinal biopsy in a high proportion of patients (78%). Jejunal biopsy would be necessary in patients with discordant antibody results (22%). With this two-step procedure, only patients with no CD-specific antibodies would be missed. PMID:23343249

2013-01-01

324

Prenatal passive transfer of Mycobacterium tuberculosis antibodies in Asian elephant (Elephas maximus) calves.  

PubMed

Asian elephant (Elephas maximus) dams and their newborn calves were tested for Mycobacterium tuberculosis antibodies in serum. Blood was drawn from dams prior to calving and from calves on their day of birth. All six calves born to tuberculosis-reactive dams were also tuberculosis reactive, suggesting prenatal passive placental transfer of tuberculosis antibodies. In contrast, all three calves born to tuberculosis-nonreactive dams lacked detectable tuberculosis antibodies in pre-suckling or day-of-birth blood samples. Of the living tuberculosis-reactive calves observed from 1 to 11 yr of age, none exhibited clinical signs of tuberculosis infection or became tuberculosis culture positive. This is the first report of prenatal passive placental transfer of tuberculosis antibodies in elephants and demonstrates that detectible tuberculosis antibodies in newborn elephant calves should not be assumed to correlate with clinical tuberculosis. PMID:25632691

McGee, Jennifer L; Wiedner, Ellen; Isaza, Ramiro

2014-12-01

325

Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.  

PubMed Central

Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with cardiolipin binding activity were subsequently eluted from these platelets. Total phospholipids extracted from platelets inhibited aCL activity, and the specific phospholipids bound were shown to be phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. It is concluded that aCL antibodies can bind phospholipids in platelet membranes but pertubation of the membrane must first occur. Images PMID:3196084

Khamashta, M A; Harris, E N; Gharavi, A E; Derue, G; Gil, A; Vázquez, J J; Hughes, G R

1988-01-01

326

Serologic survey of antibodies to Trypanosoma cruzi in coyotes and red foxes from Pennsylvania and Tennessee.  

PubMed

Trypanosoma cruzi is a zoonotic parasite of humans and other mammalian hosts with distribution throughout the Americas. Domestic and wild canine species are reservoirs for human T. cruzi infections. The present study examined the prevalence of antibodies to T. cruzi in wild canids from the United States. Sera from 13 red foxes (Vulpes vulpes) and 263 coyotes (Canis latrans), originating in Pennsylvania and Tennessee, were assayed for antibodies to T. cruzi with immunochromatographic tests. Antibodies to T. cruzi were found in 2 of 276 (0.72%) of all wild canids tested. Both T. cruzi-positive wild canids were coyotes and represented 2 of 21 (9.52%) wild canids assayed from Tennessee. Antibodies to T. cruzi were not detected in red fox. Anti-T. cruzi antibodies were not found in any wild canids from Pennsylvania. These results suggest that coyotes are exposed to T. cruzi in Tennessee but not in Pennsylvania. PMID:25632700

Rosypal, Alexa C; Smith, Trynecia; Alexander, Andrew; Weaver, Melanie; Stewart, Richard; Houston, Allan; Gerhold, Richard; Van Why, Kyle; Dubey, Jitender P

2014-12-01

327

Gene silencing results in instability of antibody production in transgenic plants.  

PubMed

The stability of antibody and Fab expression was assessed in five different homozygous transgenic Arabidopsis lines. Each of these lines showed silencing of the transgenes that encode the antibody polypeptides, leading to instability of antibody production. However, each line had a different and specific instability profile. The characteristic variation in the level of antibody accumulation in each line as a function of developmental stage indicated that the T-DNA integration pattern played a role in triggering silencing, and also that the history and the integration position of simple transgene loci can influence the susceptibility to epigenetic silencing. In different lines with low antibody accumulation levels, methylation was found either in the promoter alone, in both the promoter and the transcribed region, in the transcribed region only, or in the transcribed region and downstream sequences. In conclusion, our data suggest that epigenetic effects result in different transgene expression profiles in each of the five Arabidopsis lines analyzed. PMID:9928938

De Neve, M; De Buck, S; De Wilde, C; Van Houdt, H; Strobbe, I; Jacobs, A; Van Montagu; Depicker, A

1999-01-01

328

Immunotypes of a Quaternary Site of HIV-1 Vulnerability and Their Recognition by Antibodies?  

PubMed Central

HIV-1 is neutralized by a class of antibodies that preferentially recognize a site formed on the assembled viral spike. Such quaternary structure-specific antibodies have diverse neutralization breadths, with antibodies PG16 and PG9 able to neutralize 70 to 80% of circulating HIV-1 isolates while antibody 2909 is specific for strain SF162. We show that alteration between a rare lysine and a common N-linked glycan at position 160 of HIV-1 gp120 is primarily responsible for toggling between 2909 and PG16/PG9 neutralization sensitivity. Quaternary structure-specific antibodies appear to target antigenic variants of the same epitope, with neutralization breadth determined by the prevalence of recognized variants among circulating isolates. PMID:21325411

Wu, Xueling; Changela, Anita; O'Dell, Sijy; Schmidt, Stephen D.; Pancera, Marie; Yang, Yongping; Zhang, Baoshan; Gorny, Miroslaw K.; Phogat, Sanjay; Robinson, James E.; Stamatatos, Leonidas; Zolla-Pazner, Susan; Kwong, Peter D.; Mascola, John R.

2011-01-01

329

Limited interlaboratory comparison of Schmallenberg virus antibody detection in serum samples.  

PubMed

Eight veterinary institutes in seven different countries in Europe participated in a limited interlaboratory comparison trial to evaluate laboratory performances of Schmallenberg virus (SBV) antibody detection in serum. Seven different sheep sera and three different cattle sera were circulated, and all participating institutes were asked to test these sera using SBV antibody detection assay(s) in place in their laboratories. All laboratories within the trial performed a virus neutralisation test (VNT) as well as one or two ELISAs on all samples, and swiftly detected SBV antibodies using these assays. VNT was more sensitive in detecting SBV antibodies than several of the used ELISA assays. Based on the test results, one cattle and one sheep SBV antibody-positive serum were selected to serve as reference sera, which now can be supplied to other laboratories on request. PMID:24591480

van der Poel, W H M; Cay, B; Zientara, S; Steinbach, F; Valarcher, J F; Bøtner, A; Mars, M H; Hakze-van der Honing, R; Schirrmeier, H; Beer, M

2014-04-12

330

Anti-HLA and Anti-MICA Antibodies in Liver Transplant Recipients: Effect on Long-Term Graft Survival  

PubMed Central

Objective. Presence of anti-HLA antibodies has a well-known impact on kidney grafts survival; however their role in liver transplantation has not been fully elucidated. We conducted a 7-year prospective study to show correlation between presence of anti-HLA and anti-MICA antibodies and liver graft survival. Methods. Blood samples from 123 liver transplant recipients were collected during patients routine visits. Time from transplantation to blood sample collection was different for each patient. Blood samples were tested for anti-HLA (separately class I and II) and MICA antibodies using Luminex assays. Results. There were 32 (26%) patients with positive anti-HLA and 37 (30%) with positive anti-MICA antibodies. Graft loss occurred in 7 cases (23%) in anti-HLA positive group compared to 20 (22%) in anti-HLA negative group (P = ns) and in 8 cases (22%) in anti-MICA positive group but 19 (23%) in anti-MICA negative group (P = ns). No correlations were detected between presence of antibodies and acute graft rejection (AGR). Presence of any antibodies (anti-HLA or anti-MICA antibodies) correlated with late graft rejection (P = 0.04). Conclusion. Presence of anti-HLA or anti-MICA had no impact on long-term liver graft survival; however, detection of any antibodies was correlated with episodes of late graft rejection. PMID:24369475

Foroncewicz, Bartosz; Mucha, Krzysztof; ?ochowska, Dorota; Ziarkiewicz-Wróblewska, Bogna; Krawczyk, Marek; P?czek, Leszek

2013-01-01

331

Antibodies to egg?drop syndrome 76 virus in wild birds in possible conjunction with egg?shell problems  

Microsoft Academic Search

Antibodies against egg drop syndrome 1976 (EDS 76) virus (strain 127) were detected with the aid of the haemagglutination inhibition test and virus neutralisation test in serum samples of two out of 381 owls, in one out of four storks, in one out of two swans and in one out of 18 wild geese. The antibody positive two owls and

E. F. Kaleta; S. E. D. Khalaf; O. Siegmann

1980-01-01

332

Monoclonal Antibodies for the Treatment of Cancer  

PubMed Central

Over the past decade, the clinical utility of monoclonal antibodies has been realized and antibodies are now a mainstay for the treatment of cancer. Antibodies have the unique capacity to target and kill tumor cells while simultaneously activating immune effectors to kill tumor cells through the complement cascade or antibody-dependent cellular cytotoxicity (ADCC). This multifaceted mechanism of action combined with target specificity underlies the capacity of antibodies to elicit anti-tumor responses while minimizing the frequency and magnitude of adverse events. This review will focus on mechanisms of action, clinical applications and putative mechanisms of resistance to monoclonal antibody therapy in the context of cancer. PMID:22245472

Shuptrine, Casey; Surana, Rishi; Weiner, Louis M.

2012-01-01

333

Single-domain antibody-based and linker-free bispecific antibodies targeting Fc?RIII induce potent antitumor activity without recruiting regulatory T cells.  

PubMed

Antibody-dependent cell-mediated cytotoxicity, one of the most prominent modes of action of antitumor antibodies, suffers from important limitations due to the need for optimal interactions with Fc? receptors. In this work, we report the design of a new bispecific antibody format, compact and linker-free, based on the use of llama single-domain antibodies that are capable of circumventing most of these limitations. This bispecific antibody format was created by fusing single-domain antibodies directed against the carcinoembryonic antigen and the activating Fc?RIIIa receptor to human C? and CH1 immunoglobulin G1 domains, acting as a natural dimerization motif. In vitro and in vivo characterization of these Fab-like bispecific molecules revealed favorable features for further development as a therapeutic molecule. They are easy to produce in Escherichia coli, very stable, and elicit potent lysis of tumor cells by human natural killer cells at picomolar concentrations. Unlike conventional antibodies, they do not engage inhibitory Fc?RIIb receptor, do not compete with serum immunoglobulins G for receptor binding, and their cytotoxic activity is independent of Fc glycosylation and Fc?RIIIa polymorphism. As opposed to anti-CD3 bispecific antitumor antibodies, they do not engage regulatory T cells as these latter cells do not express Fc?RIII. Studies in nonobese diabetic/severe combined immunodeficient gamma mice xenografted with carcinoembryonic antigen-positive tumor cells showed that Fab-like bispecific molecules in the presence of human peripheral blood mononuclear cells significantly slow down tumor growth. This new compact, linker-free bispecific antibody format offers a promising approach for optimizing antibody-based therapies. PMID:23757164

Rozan, Caroline; Cornillon, Amélie; Pétiard, Corinne; Chartier, Martine; Behar, Ghislaine; Boix, Charlotte; Kerfelec, Brigitte; Robert, Bruno; Pèlegrin, André; Chames, Patrick; Teillaud, Jean-Luc; Baty, Daniel

2013-08-01

334

Catalytic antibodies with acetylcholinesterase activity.  

PubMed

We describe three catalytic cholinesterase-like catalytic antibodies (Ab1), as well as anti-idiotypic (Ab2) and idiotypic (Ab3) antibodies, to one of the Ab1s. The Ab1s were raised against the human erythrocyte acetylcholinesterase (AChE), and are unusual in that they both recognise and resemble acetylcholinesterase in their catalytic activity. No contamination of the antibody preparations with either acetylcholinesterase or butyrylcholinesterase (BChE) was found. None of the Ab2s showed catalytic activity, whereas four Ab3s did (an incidence of 1.26% of all Ab3s). Although there is considerable resemblance between Ab1s and Ab3s, there are significant differences between the two groups. All the antibodies were inhibited by phenylmethylsulphonyl fluoride (PMSF), indicating the presence of a serine residue in their active sites, and were inhibited by the cholinesterase active site inhibitors iso-OMPA and pyridostigmine, suggesting the similarity of the sites to those of cholinesterases. The Ab3s resemble the Ab1s in their ability to hydrolyse both acetyl and butyrylthiocholine (BTCh). However, the Ab3s appear to be better catalysts, having significantly reduced K(m) values (for acetyl, but not for butyrylthiocholine) and increased turnover numbers (K(cat)), rate enhancements (K(cat)/K(uncat)) and K(cat)/K(m) ratios, for both substrates, although these values by no means approach those of the natural enzymes. The Ab1s appear to have structures resembling the anionic sites of cholinesterases, as shown by their reaction with the anionic site inhibitors (edrophonium and tetramethylammonium). No such reactions were observed in the Ab3s. None of the antibodies show evidence of the sites resembling the peripheral anionic site (PAS) of acetylcholinesterase. All the antibodies recognise, to varying degrees, the peripheral anionic site of acetylcholinesterase. This was shown by their ability to inhibit acetylcholinesterase, to compete with peripheral site inhibitors, and to block acetylcholinesterase-mediated cell adhesion, a property of this site. The results indicate idiotypic mimicry of a catalytic antibody's active site, and suggest that the development of the catalytic activity in the anti-acetylcholinesterase antibodies may be related to the structural features of the peripheral anionic site of acetylcholinesterase. PMID:12379349

Johnson, Glynis; Moore, Samuel W

2002-11-01

335

Pre-existing anti-HLA antibodies negatively impact survival of pediatric aplastic anemia patients undergoing HSCT.  

PubMed

Graft failure and survival are the major problems for patients with aplastic anemia undergoing hematopoietic stem cell transplantation (HSCT). Previous studies showed that anti-HLA antibodies negatively impact engraftment in HSCT. This retrospective study of 51 pediatric patients with acquired aplastic anemia who underwent allogeneic HSCT at a single institution between 2006 and 2012 investigated the influence of anti-HLA antibodies on the outcome of HSCT. Serum samples collected before HSCT were tested for the presence of anti-HLA antibodies. Pre-existing anti-HLA antibodies were detected in 54.9% (28/51) of patients, among whom 39.2% (20/51) had anti-HLA class I antibodies. Anti-HLA antibodies were associated with worse five-yr survival (78.6% vs. 100%, p = 0.021) and higher treatment-related mortality (21.4% vs. 0%, p = 0.028) compared with antibody-negative patients. Anti-HLA class I antibody-positive patients had poorer five-yr survival (75.0%) than anti-HLA class I&II antibody-positive and antibody-negative patients (87.5% and 100.0%, respectively, p = 0.039). Presence of anti-HLA class I antibodies (p = 0.024) and older age (10 yr or more; p = 0.027) significantly increased the risk of post-HSCT mortality. Pre-existing anti-HLA antibodies negatively affect the outcome of HSCT in pediatric patients with aplastic anemia. Routine testing for anti-HLA antibodies concurrent with efficient treatment should be conducted prior to HSCT. PMID:25123053

Zhu, Hua; He, Jun; Cai, Junchao; Yuan, Xiaoni; Jiang, Hua; Luo, Changying; Wang, Jianmin; Luo, Chengjuan; Pan, Zhijuan; Terasaki, Paul I; Ding, Lixia; Chen, Jing

2014-11-01

336

B cell responses to HIV and the development of human monoclonal antibodies.  

PubMed Central

In this review B cell responses in HIV-infected individuals are summarized together with the techniques used to date to produce human monoclonals to HIV and the properties of these antibodies. Profound disturbances in B cell responses are apparent both in vivo and in vitro. While there is evidence in vivo of marked polyclonal B cell activation, primary and secondary antibody responses are impaired. Similarly these cells exhibit spontaneous immunoglobulin secretion upon in vitro culture but do not readily respond to B cell mitogens and recall antigens including HIV. Furthermore, certain of these defects can be reproduced in normal B cells in vitro by incubation with HIV or HIV coded peptides. Individuals infected with HIV develop antibodies to HIV structural proteins (e.g. p17, p24, gp41 and gp120) and regulatory proteins (e.g. vif, nef, RT). Autoantibodies against a number of immunologically important molecules are also frequently observed. The anti-HIV antibodies are predominantly of the IgG1 isotype and exhibit a variety of effects on the virus in vitro. To date, using conventional immortalization strategies, an appreciable number of human monoclonals to HIV have been developed. These have been specific for gp41, gp120 and gag with antibodies of the former specificity predominating. The majority of these antibodies have been of the IgG1 isotype. Only a small number of the antibodies neutralize virus in vitro and most of these react with gp120. The neutralizing antibodies recognize conformational and carbohydrate epitopes or epitopes in amino acid positions 306-322. The predominant epitopes recognized by the anti-gp41 antibodies were in amino acid positions 579-620 and 644-662. A high percentage (congruent to 25%) of these antibodies enhance viral growth in vitro. The problems relating to the production of human monoclonals to HIV are discussed together with strategies that could be used in the future. PMID:1572084

Boyd, J E; James, K

1992-01-01

337

Seroprevalence of Sarcoptes scabiei var canis antibodies among aborigines in peninsular Malaysia.  

PubMed

The Aborigines or Orang Asli in Peninsular Malaysia who are still seminomadic are known to have a close association with dogs. In this study, enzyme-linked immunosorbent assay (ELISA) was used to detect anti-Sarcoptes scabiei var canis antibodies in this community as a measure of exposure to the mite. Out of 312 Orang Asli tested, 24.7% were positive for polyvalent anti-Sarcoptes antibodies. No significant difference was found between the positive rates in males (26.1%) and females (23.6%). Only 1.9% were positive for IgA and none was positive for IgE anti-Sarcoptes antibodies. Since there were very few patients with clinical manifestation of scabies, there is a possibility that continuous exposure to the dogs mite confers cross-protective immunity in the community against human scabies. PMID:9031401

Normaznah, Y; Saniah, K; Nazma, M; Mak, J W; Krishnasamy, M; Hakim, S L

1996-03-01

338

Crescentic Glomerulonephritis with Anti-GBM and p-ANCA Antibodies.  

PubMed

We are presenting a case of renal failure with anti-GBM and p-ANCA antibodies positive. Patients with dual antibodies are considered to be a vasculitis-variant of anti-GBM antibody nephritis. These patients may have atypical presentation and it may delay diagnosis and treatment. Recurrence rate is higher in these patients. We reviewed the literature of cases and studies on cresenteric glomerulonephritis with anti-GBM and p-ANCA positive patients. We recommend that patients suspected with pulmonary-renal syndrome should be checked for anti-GBM and p-ANCA antibodies, should undergo renal biopsy and should should have close long term follow up to watch for recurrence. PMID:24527239

Javed, Tariq; Vohra, Parag

2012-01-01

339

Crescentic Glomerulonephritis with Anti-GBM and p-ANCA Antibodies  

PubMed Central

We are presenting a case of renal failure with anti-GBM and p-ANCA antibodies positive. Patients with dual antibodies are considered to be a vasculitis-variant of anti-GBM antibody nephritis. These patients may have atypical presentation and it may delay diagnosis and treatment. Recurrence rate is higher in these patients. We reviewed the literature of cases and studies on cresenteric glomerulonephritis with anti-GBM and p-ANCA positive patients. We recommend that patients suspected with pulmonary-renal syndrome should be checked for anti-GBM and p-ANCA antibodies, should undergo renal biopsy and should should have close long term follow up to watch for recurrence. PMID:24527239

Javed, Tariq; Vohra, Parag

2012-01-01

340

Antibody response to Hepatozoon canis in experimentally infected dogs.  

PubMed

Canine hepatozoonosis is a disease caused by the tick-borne protozoan Hepatozoon canis. Five puppies were inoculated by ingestion of Rhipicephalus sanguineus ticks experimentally infected with H. canis, and all became infected with H. canis: gametocytes were detected in blood smears from four dogs and schizonts were observed in the spleen and bone marrow of the fifth. Antibodies reactive with H. canis gametocytes were detected by the indirect fluorescent antibody test (IFA), with IgM detected initially in all dogs 16 to 39 days post infection (PI) and IgG 22 to 43 days PI. The presence of gametocytes was first observed within peripheral blood neutrophils in Giemsa-stained blood smears between days 28 and 43 PI. Gametocyte-reactive antibodies were detected before the appearance of blood gametocytes in three of the four parasitemic dogs and also in a dog with no observed parasitemia. The detection of serum antibodies prior to the detection of blood gametocytes, or without apparent parasitemia, suggests that antibodies reactive with gametocytes may be formed against earlier forms of the parasite developing in the parenchymal tissues. Sera of dogs experimentally infected with Babesia canis, Babesia gibsoni and Ehrlichia canis exhibited no reactivity when tested with H. canis antigen. Additionally, sera positive for H. canis were not reactive with antigens of Toxoplasma gondii, Neospora caninum, Leishmania donovani and E. canis. In conclusion, incoculation of dogs with ticks infected with H. canis results in production of antibodies reactive with peripheral blood gametocytes. Detection of IgG titres would be beneficial for the diagnosis of progressive infections with undetectable parasitemia, for seroprevalence studies, and as an adjunct to IgM titres in early infections. PMID:9561714

Baneth, G; Shkap, V; Samish, M; Pipano, E; Savitsky, I

1998-01-31

341

Serum antibodies to oral Bacteroides asaccharolyticus (Bacteroides gingivalis): relationship to age and periondontal disease.  

PubMed Central

An enzyme-linked immunosorbent assay microplate method was used for measuring levels of antibody specific for the oral serotype of Bacteroides asaccharolyticus (Bacteroides gingivalis) in serum samples obtained from umbilical cords, infants, children, periodontally normal adults, and edentulous adults. Serum from patients with various periodontal diseases, including adult periodontitis, localized juvenile periodontitis, generalized juvenile periodontitis, post-localized juvenile periodontitis, and acute necrotizing ulcerative gingivitis, were also studied. A positive correlation between increase in age and increase in both prevalence and level of specific antibody in the G, A, and M classes of immunoglobulins was observed. This indicates that antibodies reactive with oral B. asaccharolyticus found in up to 84% of normal adults are natural antibodies, presumably with a protective role. Among the patient groups, those with adult periodontitis were found to have levels of immunoglobulin G antibodies to oral B. asaccharolyticus that were five times higher than the antibody levels found in control subjects. The levels of IgG antibodies to this organism in the other patient groups were comparable to the levels found in the control group. However, 50% of the individuals in the generalized juvenile periodontitis group had high levels of immunoglobulin G antibodies to B. asaccharolyticus, suggesting heterogeneity with respect to immune response in these patients. These results indicate that antibodies to oral B. asaccharolyticus (B. gingivalis) occur at low levels in most normal children and adults and that the rise in titer of the specific antibodies of each major class of immunoglobulins parallels the ontogenic change in serum levels of that isotype. In contrast, there is a marked increase in titer of immunoglobulin G antibodies to oral B. asaccharolyticus in the group of patients with adult periodontitis and in patients with the generalized form of juvenile periodontitis. Images PMID:7216444

Mouton, C; Hammond, P G; Slots, J; Genco, R J

1981-01-01

342

Prevalence of Strongyloides stercoralis antibodies among a rural Appalachian population--Kentucky, 2013.  

PubMed

We investigated whether Strongyloides infection remains endemic in rural Kentucky's Appalachian regions; 7 of 378 (1.9%) participants tested positive for Strongyloides antibodies. We identified no statistically significant association between a positive test and travel to a known endemic country (P = 0.58), indicating that transmission in rural Kentucky might be ongoing. PMID:25157122

Russell, Elizabeth S; Gray, Elizabeth B; Marshall, Rebekah E; Davis, Stephanie; Beaudoin, Amanda; Handali, Sukwan; McAuliffe, Isabel; Davis, Cheryl; Woodhall, Dana

2014-11-01

343

Characterization of antibodies directed against platelet cryptantigens detected during the immunological study of 356 consecutive patients with presumed autoimmune thrombocytopenia (AITP).  

PubMed

Cryptic antigens are detected by antibodies present in a wide spectrum of patients with or without thrombocytopenia, and even in healthy individuals. They are produced for unknown reasons and do not react with antigens of native platelets, but only with altered platelets. Cryptantigen antibodies may not only result in spuriously low platelet counts, but also in 'falsely' positive tests for platelet antibodies. We report our experience in the characterization of the different types of antibodies directed against cryptantigens of platelets: EDTA-dependent antibodies, PFA-dependent antibodies, EDTA-PFA-dependent antibodies and cold agglutinins. These antibodies were detected in the course of the serological study of 37 patients from a group of 356 (10%) whose blood was sent to our laboratory for platelet antibody testing. Pseudothrombocytopenia was diagnosed in 24 cases. Twenty-one of these showed EDTA-dependent or EDTA-PFA-dependent platelet agglutination and three were due to the presence of cold agglutinins. In 13 patients the thrombocytopenia was genuine. Eleven of these presented EDTA-dependent or EDTA-PFA-dependent antibodies in their serum and in the two remaining cases PFA-dependent antibodies were found. Cryptantigen antibodies were also detected in 9 out of 228 (4%) blood donors who were used as healthy controls in the platelet immunofluorescence test. In the light of the results obtained we put forward some guidelines to detect the presence of these antibodies and establish an accurate serological and clinical diagnosis of the autoimmune thrombocytopenias. PMID:8593522

Muñiz-Diaz, E; Madoz, P; Pujol-Moix, N; Pastoret, C; Arilla, M; Ibañez, M; Guanyabens, C; Domingo-Albós, A

1995-09-01

344

Evaluation of antibodies reactive with Campylobacter jejuni in Egyptian diarrhea patients.  

PubMed Central

Serum and stool samples were collected from 128 individuals: 96 diarrhea patients and 32 apparently healthy controls. Stool specimens were cultured for enteric bacterial pathogens, while sera were screened by enzyme-linked immunosorbent assay for Campylobacter jejuni-reactive antibodies. Of 28 diarrhea patients who demonstrated C. jejuni-reactive antibodies (titers, > 100), 14 were culture positive for this organism. The 32 healthy controls showed significantly lower antibody titers (P < 0.05) with the exception of 10 subjects who were culture positive for C. jejuni and had reactive immunoglobulin M (IgM) (6 subjects) and IgG (7 subjects). IgA was not detected in those 10 individuals (asymptomatic). Avidity was expressed as the thiocyanate ion concentration required to inhibit 50% of the bound antibodies. The avidity was higher in symptomatic patients than asymptomatic healthy controls. IgG was less avid (0.92 M) compared to IgM (0.1 M) and IgA (1.1 M), with no correlation between antibody titer and avidity. However, the thiocyanate ion concentration required for the complete inhibition of IgG (5 M)-bound antibodies was higher than that of IgA (2 M) and IgM (3 M). This study also shows that C. jejuni antibodies were variably cross-reactive with Escherichia coli, Shigella flexneri, Shigella sonnei, and Neisseria meningitidis in addition to Campylobacter coli and Campylobacter rectus. PMID:9302201

Ismail, T F; Wasfy, M O; Oyofo, B A; Mansour, M M; El-Berry, H M; Churilla, A M; Eldin, S S; Peruski, L F

1997-01-01

345

New Insights into the Functional Behavior of Antibodies as Revealed by Binding Studies on an Anti-Uranium Monoclonal Antibody  

SciTech Connect

As part of an ongoing effort to develop immunoassays for chelated uranium(VI) on a hand-held flow fluorimeter, an anti-uranium monoclonal antibody designated as 8A11 was fluorescently labeled using two different strategies. When 8A11 was coupled via reactive lysines to either ALEXATM 488 or Cy5TM, the resulting fluorescent antibody conjugate exhibited positive cooperativity in the presence of its antigen, U(VI) chelated with 2,9-dicarboxy-1,10-phenanthroline (U(VI)-DCP). That is, when one of the two binding sites on the covalently modified 8A11 was occupied with bound antigen, the affinity of the remaining site on the antibody for U(VI)-DCP appeared to increase. Unmodified 8A11 bound U(VI)-DCP with the expected hyperbolic dependence on the concentration of antigen, consistent with independent and equal binding of ligand at both sites. Proteolytic cleavage of the fluorescently conjugated 8A11 to produce the fluorescent monovalent Fab fragment yielded an active preparation that now bound U(VI)-DCP with no evidence of positive cooperativity. Although, in principle, any divalent antibody has the potential to exhibit positive cooperativity in its binding interactions with its antigen, very little literature precedent for this type of behavior exists. Native 8A11 was also noncovalently labeled with highly fluorescent ZENONTM reagents. These reagents are fluorescently-labeled Fab fragments of goat anti-mouse antibodies that bind to the Fc portion of 8A11. These high-affinity, monovalent fluorescent reagents permitted the intact 8A11 mouse antibody to be labeled in situ with no covalent modifications. Incubation of the 8A11 with ZENON 647 produced a fluorescent protein complex that showed an 8-fold higher affinity for U(VI)-DCP than did the free 8A11 alone. Again, very few literature precedents exist for this phenomenon, where agents that bind to the Fc portion of an intact antibody change the affinity of the antibody for the antigen at the structurally distant Fab portion of the molecule. The addition of protein G, a bacterial protein that also binds to the Fc portion of mouse IgG, to the covalently modified 8A11 produced an antibody preparation that showed a lower affinity for U(VI)-DCP than that observed in the absence of protein G. This protein G-dependent decrease in the affinity of 8A11for U(VI)-DCP was dose-dependent. Similarly, U(VI)-DCP was observed to decrease the affinity between 8A11 and protein G, also in a dose-dependent manner. These reciprocal binding effects between protein G and U(VI)-DCP were taken as further evidence that binding to the Fc portion on the intact 8A11 antibody could influence the strength of the interaction at the antigen binding sites on the Fab portions of the protein, and vice versa. These practical, development-driven binding experiments have revealed a fundamental facet of antibody functional behavior that appears to have been largely unnoticed. The binding phenomena described for the first time in this report may have physiological relevance and can be purposefully exploited to improve the sensitivity and utility of selected immunoassays.

Blake, Diane A.; Xia Li; Haini Yu; Blake, Robert C.

2004-03-17

346

[Neuroimmunological diseases associated with VGKC complex antibodies].  

PubMed

Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. PMID:23777104

Watanabe, Osamu

2013-05-01

347

Antiphospholipid Antibodies: Findings at Arteriography  

Microsoft Academic Search

PURPOSE: The purpose of this study was to determine the frequency and types of abnor- malities at arteriography in patients with antiphospholipid antibodies (APA) and ischemic cerebrovascular events. METHODS: Twenty-three patients with APA and ischemic cerebrovascular events who un- derwent arteriography were identified. Patients over the age of 65 years were excluded. No patients met diagnostic criteria for systemic lupus

James M. Provenzale; Daniel P. Barboriak; Nancy B. Allen; Thomas L. Ortel

348

Serologic survey for Coxiella burnetii phase II antibodies among slaughterhouse workers in Kerman, southeast of Iran  

PubMed Central

Objective To determine the presence of antibodies against phase II among slaughterhouse workers in Kerman, southeast of Iran. Methods The antibody titers of the serum samples were measured by enzyme-linked immuno sorbent assay using phase II Coxiella burnetii as the antigen [kit (Virion\\Serion, Wurzburg, Germany) according to the manufacturer's protocol]. Results The positive rate of IgG antibody was 68% in the slaughterhouse workers. Conclusions Our findings suggest that slaughterhouse workers in Kerman area have a higher risk of infection and should consider potential infection with Coxiella burnetii. PMID:25183082

Khalili, Mohammad; Mosavi, Morteza; Diali, Hamzeh Ghobadian; Mirza, Hossein Norouzian

2014-01-01

349

TNF-? and antibodies to periodontal bacteria discriminate between Alzheimer’s disease patients and normal subjects  

PubMed Central

The associations of inflammation/immune responses with clinical presentations of Alzheimer’s disease (AD) remain unclear. We hypothesized that TNF-? and elevated antibodies to periodontal bacteria would be greater in AD compared to normal controls (NL) and their combination would aid clinical diagnosis of AD. Plasma TNF-? and antibodies against periodontal bacteria were elevated in AD patients compared with NL and independently associated with AD. The number of positive IgG to periodontal bacteria incremented the TNF-? classification of clinical AD and NL. This study shows that TNF-? and elevated numbers of antibodies against periodontal bacteria associate with AD and contribute to the AD diagnosis. PMID:19767111

Kamer, Angela R.; Craig, Ronald G.; Pirraglia, Elizabeth; Dasanayake, Ananda P.; Norman, Robert G.; Boylan, Robert J.; Nehorayoff, Andrea; Glodzik, Lidia; Brys, Miroslaw; de Leon, Mony J.

2009-01-01

350

Mammalian cell display for the discovery and optimization of antibody therapeutics.  

PubMed

Recent advances are described for the isolation and affinity maturation of antibodies that couple in vitro somatic hypermutation (SHM) with mammalian cell display, replicating key aspects of the adaptive immune system. SHM is dependent on the action of the B cell specific enzyme, activation-induced cytidine deaminase (AID). AID-directed SHM in vitro in non-B cells, combined with mammalian display of a library of human antibodies, initially naïve to SHM, can be used to isolate and affinity mature antibodies via iterative cycles of fluorescence-activated cell sorting (FACS) under increasingly stringent sort conditions. SHM observed in vitro closely resembles SHM observed in human antibodies in vivo in both mutation type and positioning in the antibody variable region. In addition, existing antibodies originating from mouse immunization, in vivo based libraries, or alternative display technologies such as phage can also be affinity matured in a similar manner. The display system has been developed to enable simultaneous high-level cell surface expression and secretion of the same protein through alternate splicing, where the displayed protein phenotype remains linked to genotype, allowing soluble secreted antibody to be simultaneously characterized in biophysical and cell-based functional assays. This approach overcomes many of the previous limitations of mammalian cell display, enabling direct selection and maturation of antibodies as full-length, glycosylated IgGs. PMID:23792919

Bowers, Peter M; Horlick, Robert A; Kehry, Marilyn R; Neben, Tamlyn Y; Tomlinson, Geoffery L; Altobell, Larry; Zhang, Xue; Macomber, John L; Krapf, Irina P; Wu, Betty F; McConnell, Audrey D; Chau, Betty; Berkebile, Ashley D; Hare, Eric; Verdino, Petra; King, David J

2014-01-01

351

Clinical and therapeutic aspects associated to phospholipid binding antibodies (lupus anticoagulant and anticardiolipin antibodies).  

PubMed

Antiphospholipid antibodies (APA) comprise a family of immunoglobulins characterized by their pattern of reactivity in a number of laboratory tests. Included in this family are lupus anticoagulant (LA) anticardiolipin antibodies (ACA) and antibodies causing biologic false positive serologic tests for syphilis (BFP-STS). LA and ACA occur in a variety of conditions, including other autoimmunes disorders, infectious diseases, neoplasic disorders, in association with certain drugs and in otherwise healthy individuals. Clinical interest in LA and ACA is increasing. Antiphospholipid antibody syndrome is characterized by a triad of clinical features which include fetal loss, thromboembolic disease and thrombocytopenia. Other clinical manifestations related with APA are livedo reticularis, cutaneous necrosis, hemolytic anemia, heart valve disease, chorea, migraine and obstetric problems as fetal growth retardation, pre-eclampsia, post-partum serositis or neonatal thrombosis or catastrophic antiphospholipid syndrome. Therapy is mainly directed against the widespread and diverse manifestations associated with the obstruction of small and large vessels. Long-term treatment with oral anticoagulation therapy is advised, even if the venous or arterial occlusion occurred many years previously. In patients with primary antiphospholipid syndrome there is no evidence that the prophylactic administration of steroids or immunosuppression will prevent thromboembolic events. Although the administration of more energetic immunosuppression with cyclophosphamide in pulse form is effective in reducing elevated antibody levels, there is usually a rapid rebound to pretreatment levels shortly after discontinuation of the therapy. A history of recurrent fetal loss requires mandatory treatment during pregnancy. Although the actual prospective risk of pregnancy loss in women with antiphospholipid syndrome and prior pregnancy loss is unknown, it may exceed 60%. Because of this many investigators have treated women with antiphospholipid syndrome with either antiplatelet agents, immunosuppressive agents, or anticoagulants in an attempt to improve pregnancy outcome. Unfortunately, there is no unequivocal proof that any of these therapies are fully efficacious. Despite varying treatment protocols, the live birth rate with treatment was 70%, similar to that reported in the recent randomized clinical trial. Thrombocytopenia and autoimmune hemolytic anemia in patients with APA are treated similarly as patients without APA. Treatment of asymptomatic patients isn't indicated, because only approximately 10-15% of patients with APA developed complications. PMID:7988946

Ordi-Ros, J; Pérez-Pemán, P; Monasterio, J

1994-01-01

352

Antiphospholipid Antibodies and Stroke in Young Women  

Microsoft Academic Search

Background and Purpose—Antiphospholipid antibodies have been associated with ischemic stroke in some but not all studies. Methods—We performed a population-based case-control study examining antiphospholipid antibodies (anticardiolipin antibodies and lupus anticoagulants) using stored frozen sera and plasma in 160 cases and 340 controls enrolled in the Stroke Prevention in Young Women study. We evaluated for the presence of anticardiolipin antibody (IgG,

Robin L. Brey; Christian L. Stallworth; David L. McGlasson; Marcella A. Wozniak; Robert J. Wityk; Barney J. Stern; Michael A. Sloan; Roger Sherwin; Thomas R. Price; Richard F. Macko; Constance J. Johnson; Christopher J. Earley; David W. Buchholz; J. Richard Hebel; Steven J. Kittner

353

Therapeutic antibodies for autoimmunity and inflammation  

Microsoft Academic Search

The development of therapeutic antibodies has evolved over the past decade into a mainstay of therapeutic options for patients with autoimmune and inflammatory diseases. Substantial advances in understanding the biology of human diseases have been made and tremendous benefit to patients has been gained with the first generation of therapeutic antibodies. The lessons learnt from these antibodies have provided the

Andrew C. Chan; Paul J. Carter

2010-01-01

354

Anti-DNA antibodies in SLE  

SciTech Connect

This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

Voss, E.W.

1988-01-01

355

Original article Monoclonal antibodies against goldfish  

E-print Network

immunoglobulin and antibody levels by ELISA in carp (Cyprinus carpio) AK Siwicki C Vergnet J Charlemagne M Dunier decreased until day 28. monoclonal antibody / ELISA / ELISPOT / antibody-secreting cells / Cyprinus carpio suite. anticorps monoc/ona//EL/S/Cyprinus carpio

Paris-Sud XI, Université de

356

Impact of anti-peroxynitrite-damaged-thymidine- monophosphate antibodies on disease activity in patients with systemic lupus erythematosus.  

PubMed

Present study probes the role of peroxynitrite (ONOO(-))-modified thymidine-5'-monophosphate (TMP) in SLE patients with different disease activity scores according to the SLE Disease Activity Index (SLEDAI). Serum analysis showed significant increased number of subjects positive for anti-ONOO(-)-TMP-protein antibodies in SLE patients with different SLEDAI scores. Interestingly, the levels of these antibodies were significantly higher among SLE patients, whose SLEDAI scores were ?20. In addition, a significant correlation was observed between the levels of anti-ONOO(-)-TMP-protein antibodies and the SLEDAI score (r = 0.595, p < 0.0001). In short, this study shows a positive association between anti-ONOO(-)-TMP-protein antibodies and SLEDAI. The stronger response observed in patients with higher SLEDAI scores suggests that anti-ONOO(-)-TMP-protein antibodies may be useful in evaluating the progression of SLE and in elucidating the mechanisms of disease pathogenesis. PMID:25513864

Alghasham, Abdullah; Al Salloom, Abdulaziz Am; Alghamadi, Ahmed Ss; Rasheed, Zafar

2015-01-01

357

Anti-thyroid peroxidase antibody in vitiligo: a prevalence study.  

PubMed

Aim. The aim of the study was to study the relation of vitiligo with demographic data like age, sex, and duration and determine the prevalence of thyroid autoimmunity in vitiligo patients. Materials and Methods. This study was a cross sectional study consisting of 100 patients clinically diagnosed (old and new) as having vitiligo irrespective of age or sex. Patients with known thyroid disease on supplementation therapy, or who had undergone thyroid surgery, those on antithyroid medication, patients with other causes of leukoderma, and cases who do not provide informed consent were excluded from the study. Serum TSH and anti-TPO antibodies were measured in all the patients. Results. The prevalence of anti-TPO antibody positivity was found to be 28%. Conclusion. According to our study, none of our vitiligo patients had symptoms or signs of thyroid disease at the time of presentation but, on biochemical evaluation, anti-TPO antibodies were found in a considerable number of patients. Hence, we recommend screening of these patients with thyroid antibodies. PMID:25653881

Dash, R; Mohapatra, A; Manjunathswamy, B S

2015-01-01

358

Anti-Thyroid Peroxidase Antibody in Vitiligo: A Prevalence Study  

PubMed Central

Aim. The aim of the study was to study the relation of vitiligo with demographic data like age, sex, and duration and determine the prevalence of thyroid autoimmunity in vitiligo patients. Materials and Methods. This study was a cross sectional study consisting of 100 patients clinically diagnosed (old and new) as having vitiligo irrespective of age or sex. Patients with known thyroid disease on supplementation therapy, or who had undergone thyroid surgery, those on antithyroid medication, patients with other causes of leukoderma, and cases who do not provide informed consent were excluded from the study. Serum TSH and anti-TPO antibodies were measured in all the patients. Results. The prevalence of anti-TPO antibody positivity was found to be 28%. Conclusion. According to our study, none of our vitiligo patients had symptoms or signs of thyroid disease at the time of presentation but, on biochemical evaluation, anti-TPO antibodies were found in a considerable number of patients. Hence, we recommend screening of these patients with thyroid antibodies. PMID:25653881

Dash, R.; Mohapatra, A.; Manjunathswamy, B. S.

2015-01-01

359

Recombinant antibodies and their use in biosensors.  

PubMed

Inexpensive, noninvasive immunoassays can be used to quickly detect disease in humans. Immunoassay sensitivity and specificity are decidedly dependent upon high-affinity, antigen-specific antibodies. Antibodies are produced biologically. As such, antibody quality and suitability for use in immunoassays cannot be readily determined or controlled by human intervention. However, the process through which high-quality antibodies can be obtained has been shortened and streamlined by use of genetic engineering and recombinant antibody techniques. Antibodies that traditionally take several months or more to produce when animals are used can now be developed in a few weeks as recombinant antibodies produced in bacteria, yeast, or other cell types. Typically most immunoassays use two or more antibodies or antibody fragments to detect antigens that are indicators of disease. However, a label-free biosensor, for example, a quartz-crystal microbalance (QCM) needs one antibody only. As such, the cost and time needed to design and develop an immunoassay can be substantially reduced if recombinant antibodies and biosensors are used rather than traditional antibody and assay (e.g. enzyme-linked immunosorbant assay, ELISA) methods. Unlike traditional antibodies, recombinant antibodies can be genetically engineered to self-assemble on biosensor surfaces, at high density, and correctly oriented to enhance antigen-binding activity and to increase assay sensitivity, specificity, and stability. Additionally, biosensor surface chemistry and physical and electronic properties can be modified to further increase immunoassay performance above and beyond that obtained by use of traditional methods. This review describes some of the techniques investigators have used to develop highly specific and sensitive, recombinant antibody-based biosensors for detection of antigens in simple or complex biological samples. PMID:22159424

Zeng, Xiangqun; Shen, Zhihong; Mernaugh, Ray

2012-04-01

360

Comparison of two rapid diagnostic assays for detection of immunoglobulin M antibodies to dengue virus.  

PubMed

Two easy-to-use commercial diagnostic assays, a dipstick enzyme-linked immunosorbent assay (ELISA) (Integrated Diagnostics, Baltimore, Md.) and an immunochromatographic card assay (PanBio, Brisbane, Australia) were evaluated for detection of immunoglobulin M (IgM) antibody to dengue virus with an in-house IgM antibody capture microplate ELISA as a reference assay. The dipstick ELISA was based on the indirect-ELISA format using dengue 2 virus as the only antigen and enzyme-labeled goat anti-human IgM antibody as the detector. The total assay time was 75 min. The immunochromatographic card assay was based on the antibody capture format and separately measured both anti-dengue virus IgM and IgG in the same test. Colloidal-gold-labeled anti-dengue virus monoclonal antibody bound with dengue virus 1 to 4 antigen cocktail was the detector, and anti-human IgM and IgG were the capture antibodies. The total assay time was <10 min. Sera from 164 individuals classified as either anti-dengue virus IgM positive (94) or anti-dengue virus IgM negative (70) in the reference microplate ELISA with a dengue virus 1 to 4 antigen cocktail were tested in the two commercial assays. The dipstick ELISA missed 7 of 94 positive samples, for a sensitivity of 92.6%, while the immunochromatographic card assay missed two positive samples, for a sensitivity of 97.9%. Of the 70 negative samples, four were false positive by the dipstick ELISA and two were false positive in the immunochromatographic card assay, resulting in specificities of 94.3 and 97.1%, respectively. Both commercial assays provide sensitive and specific detection of anti-dengue virus IgM antibody and could prove useful in settings where the microplate ELISA is impractical. PMID:10618287

Wu, S J; Paxton, H; Hanson, B; Kung, C G; Chen, T B; Rossi, C; Vaughn, D W; Murphy, G S; Hayes, C G

2000-01-01

361

Helicobacter pylori Antibodies and Iron Deficiency in Female Adolescents  

PubMed Central

Objective Iron deficiency (ID) is a common clinical problem worldwide, affecting primarily females. Helicobacter pylori (HP) infection has been shown to be associated with ID. The objective of this study was to define the prevalence of HP antibodies in female adolescents, and to find out if there was a correlation between HP infection and ID. The secondary aim was to study if regularly performed sporting activity, have any association to HP infection, in itself. Design A controlled clinical trial. Setting A senior high school in Gothenburg, Sweden. Subjects All female athletes at a senior high school for top-level athletes were offered to take part, and 56 athletes took part in the study. The control group consisted of a random sample of age-matched non-athlete students of which 71 entered the study. Main outcome measures Iron deficiency (ID) and iron deficiency anaemia (IDA) were defined by the use of levels of haemoglobin, serum iron, total iron-binding capacity, transferrin saturation, and serum ferritin, as previously described. HP IgG-antibodies were detected by ELISA. Results 18 of 127 (14%) adolescent females had antibodies against HP. Only 3% had IDA, while 50% had ID. In total, 66% of the HP positive females had ID compared to 48% of the negative females (p?=?0.203). No correlation between sporting activity and HP infection was found. Regarding ethnicity, 11/28 of subjects from medium-high risk areas were HP-positive, compared to 7/99 coming from low-risk areas (p<0.001). Conclusion The main finding of this study is that the prevalence of HP IgG antibodies was 14% in adolescent females. We could not find any difference regarding frequency of ID and IDA, between HP positive and negative individuals. Ethnicity is of great importance for the risk of HP infection, while sporting activity itself seems to have no association to HP-infection. PMID:25409451

Sandström, Göran; Rödjer, Stig; Kaijser, Bertil; Börjesson, Mats

2014-01-01

362

Studies Of Positive-Position-Feedback Control  

NASA Technical Reports Server (NTRS)

Report discusses theoretical and experimental studies of positive-position-feedback control for suppressing vibrations in large flexible structures. Positive-position-feedback control involves placement of actuators and sensors on structure; control voltages applied to actuators in response to outputs of sensors processed via compensator algorithm. Experiments demonstrate feasibility of suppressing vibrations by positive position feedback, and spillover of vibrational energy into uncontrolled modes has stabilizing effect if control gain sufficiently small.

Fanson, James L.; Caughey, Thomas K.

1992-01-01

363

Production of Monoclonal Antibody against Human Nestin  

PubMed Central

We have employed a peptide-based antibody generation protocol for producing antibody against human nestin. Using a 12-mer synthetic peptide from repetitive region of human nestin protein devoid of any N- or O-glyco-sylation sequences, we generated a mouse monoclonal antibody capable of recognizing human, mouse, bovine, and rat nestin. A wide variety of nestin proteins ranging from 140–250 kDa was detected by this antibody. This antibody is highly specific and functional in applications such as ELISA, flow cytometry, immunocytochemistry, and Western blot assays. PMID:23407796

Hadavi, Reza; Zarnani, Amir Hassan; Ahmadvand, Negah; Mahmoudi, Ahmad Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Sadeghi, Mohammad-Reza; Soltanghoraee, Haleh; Akhondi, Mohammad Mehdi; Tarahomi, Majid; Jeddi-Tehrani, Mahmood; Rabbani, Hodjattallah

2010-01-01

364

A method to quantitate the neutralizing capacity of anti-therapeutic protein antibodies in serum and their correlation to clinical impact.  

PubMed

A robust, quantitative method for assessing the neutralizing capacity of anti-therapeutic protein antibodies was developed and tested using 4 analytical assay platforms typically used for detection of anti-drug neutralizing antibodies. The method described here utilized titration of increasing concentrations of therapeutic protein into serum containing anti-therapeutic protein antibodies, either positive control antibodies or clinical samples. Neutralizing capacities were calculated by determining the EC50 from the titration curves. The neutralizing capacity of purified anti therapeutic protein antibodies was expressed in terms of "?g of drug neutralized per ?g of anti-TP antibody" present. In the case of serum originating from clinical study subjects, the neutralizing capacity of the samples was expressed as "?g of drug neutralized per mL of serum". A relative shift in EC50 values was observed as the amount of serum or antibody was changed resulting in a proportional shift of the calculated neutralizing capacity. Application of this approach using different assay platforms was consistent providing evidence for its potential to be a useful approach to characterize, qualify and compare neutralizing positive control antibody preparations or clinical samples. Using this methodology, we were able to draw a clear correlation between the neutralizing capacity and the effect of these antibodies on a clinical pharmacodynamic (PD) marker. Determination of the neutralizing capacity of antibody positive samples from subjects in a clinical study indicated direct correlation of pharmacodynamic results with non-response, partial response and response to high, mid and low neutralizing capacities respectively. PMID:25279937

Kaliyaperumal, Arunan; Pennucci, Jason; Nagatani, Janice; Juan, Gloria; Swanson, Steven; Gupta, Shalini

2015-01-01

365

SERUM ANTIBODIES TO BORRELIA BURGDORFERI, ANAPLASMA PHAGOCYTOPHILUM, AND BABESIA MICROTI IN RECAPTURED WHITE-FOOTED MICE  

PubMed Central

A mark-release-recapture study was conducted during 2007 through 2010 in six, tick-infested sites in Connecticut, United States to measure changes in antibody titers for Borrelia burgdorferi sensu stricto, Anaplasma phagocytophilum, and Babesia microti in Peromyscus leucopus (white-footed mice). There was an overall recapture rate of 40%, but only four tagged mice were caught in ?2 yr. Sera from 561 mice were analyzed for total antibodies to B. burgdorferi and A. phagocytophilum by using whole-cell or recombinant (VlsE or protein 44) antigens in a solid-phase enzyme-linked immunosorbent assay or to whole-cell B. microti by indirect fluorescent antibody staining. Antibody prevalences were highly variable for B. burgdorferi (from 56% to 98%), A. phagocytophilum (from 11% to 85%), and B. microti (from 11% to 84%) depending on the site and time of sampling. Of 463 mice with antibodies, 206 (45%) had antibodies to all three pathogens. Changes in antibody status for some mice from negative to positive (117 seroconversions) or from positive to negative (55 reversions) were observed. Seroconversions were observed in 10.1% of 417 mice for B. burgdorferi, 18.0% of 306 mice for A. phagocytophilum, and 6.6% of 304 mice for B. microti; reversion rates were 5.3, 5.9, and 4.9%, respectively. Antibodies to all pathogens persisted in some mice over several weeks while, in others, there were marked declines in titration end points to negative status. The latter may indicate elimination of a certain pathogen, such as A. phagocytophilum, or that mouse immune systems ceased to produce antibodies despite an existing patent infection. PMID:23568904

Magnarelli, Louis A.; Williams, Scott C.; Norris, Steven J.; Fikrig, Erol

2013-01-01

366

Application of the Filariasis CELISA Antifilarial IgG4 Antibody Assay in Surveillance in Lymphatic Filariasis Elimination Programmes in the South Pacific  

PubMed Central

Elimination of lymphatic filariasis (LF) in the Pacific Island Countries and Territories (PICT) has been defined as <0.1% circulating filarial antigen (CFA) prevalence in children born after the implementation of successful mass drug administrations (MDAs). This research assessed the feasibility of CFA and antibody testing in three countries; Tonga, Vanuatu, and Samoa. Transmission is interrupted in Vanuatu and Tonga as evidenced by no CFA positive children and a low antibody prevalence and titre. Transmission is ongoing in Samoa with microfilaraemic (Mf) and CFA positive children and a high antibody prevalence and titre. Furthermore, areas of transmission were identified with Mf positive adults, but no CFA positive children. These areas had a high antibody prevalence in children. In conclusion, CFA testing in children alone was not useful for identifying areas of residual endemicity in Samoa. Thus, it would be beneficial to include antibody serology in the PICT surveillance strategy. PMID:21961018

Joseph, Hayley; Maiava, Fuatai; Naseri, Take; Taleo, Fasihah; ‘Ake, Malakai; Capuano, Corinne; Melrose, Wayne

2011-01-01

367

Solubility evaluation of murine hybridoma antibodies  

PubMed Central

The successful development of antibody therapeutics depends on the molecules having properties that are suitable for manufacturing, as well as use by patients. Because high solubility is a desirable property for antibodies, screening for solubility has become an essential step during the early candidate selection process. In considering the screening process, we formed a hypothesis that hybridoma antibodies are filtered by nature to possess high solubility and tested this hypothesis using a large number of murine hybridoma-derived antibodies. Using the cross-interaction chromatography (CIC) method, we screened the solubility of 92 murine hybridoma-derived monoclonal antibodies and found that all of these molecules exhibited CIC profiles that are indicative of high solubility (>100mg/mL). Further investigations revealed that variable region N-linked glycosylation or isoelectric parameters are unlikely to contribute to the high solubility of these antibodies. These results support the general hypothesis that hybridoma monoclonal antibodies are highly soluble. PMID:22531448

Spencer, Stacey; Bethea, Deidra; Raju, T. Shantha; Giles-Komar, Jill; Feng, Yiqing

2012-01-01

368

Monoclonal antibodies to intermediate filament proteins of human cells: unique and cross- reacting antibodies  

PubMed Central

Monoclonal antibodies were generated against the intermediate filament proteins of different human cells. The reactivity of these antibodies with the different classes of intermediate filament proteins was determined by indirect immunofluorescence on cultured cells, immunologic indentification on SDS polyacrylamide gels (“wester blot” experiments), and immunoperoxidase assays on intact tissues. The following four antibodies are described: (a) an antivimentin antibody generated against human fibroblast cytoskeleton; (b), (c) two antibodies that recognize a 54-kdalton protein in human hepatocellular carcinoma cells; and (d) an antikeratin antibody made to stratum corneum that recognizes proteins of molecular weight 66 kdaltons and 57 kdaltons. The antivimentin antibody reacts with vimentin (58 kdaltons), glial fibrillary acidic protein (GFAP), and keratins from stratum corneum, but does not recognize hepatoma intermediate filaments. In immunofluorescence assays, the antibody reacts with mesenchymal cells and cultured epithelial cells that express vimentin. This antibody decorates the media of blood vessels in tissue sections. One antihepatoma filament antibody reacts only with the 54 kdalton protein of these cells and, in immunofluorescence and immunoperoxidase assays, only recognizes epithelial cells. It reacts with almost all nonsquamous epithelium. The other antihepatoma filament antibody is much less selective, reacting with vimentin, GFAP, and keratin from stratum corneum. This antibody decorates intermediate filaments of both mesenchymal and epithelial cells. The antikeratin antibody recognizes 66-kdalton and 57-kdalton proteins in extracts of stratum corneum and also identifies proteins of similar molecular weights in all cells tested. However, by immunofluorescence, this antibody decorates only the intermediate filaments of epidermoid carcinoma cells. When assayed on tissue sections, the antibody reacts with squamous epithelium and some, but not all, nonsquamous epithelium. Therefore this antistratum corneum antibody and the anti-54-kdalton antibody identify unique epitopes present in the various cytokeratin molecules of epithelial cells. None of the hybridoma antibodies react with neurofilament proteins. The different patterns of reactivity of these antibodies suggest that many of the immunologically distinct intermediate filament proteins contain common antigenic determinants. PMID:6183272

Gown, AM; Vogel, AM

1982-01-01

369

Mechanistic insights into the neutralization of cytotoxic abrin by the monoclonal antibody D6F10.  

PubMed

Abrin, an A/B toxin obtained from the Abrus precatorius plant is extremely toxic and a potential bio-warfare agent. Till date there is no antidote or vaccine available against this toxin. The only known neutralizing monoclonal antibody against abrin, namely D6F10, has been shown to rescue the toxicity of abrin in cells as well as in mice. The present study focuses on mapping the epitopic region to understand the mechanism of neutralization of abrin by the antibody D6F10. Truncation and mutational analysis of abrin A chain revealed that the amino acids 74-123 of abrin A chain contain the core epitope and the residues Thr112, Gly114 and Arg118 are crucial for binding of the antibody. In silico analysis of the position of the mapped epitope indicated that it is present close to the active site cleft of abrin A chain. Thus, binding of the antibody near the active site blocks the enzymatic activity of abrin A chain, thereby rescuing inhibition of protein synthesis by the toxin in vitro. At 1?10 molar concentration of abrin:antibody, the antibody D6F10 rescued cells from abrin-mediated inhibition of protein synthesis but did not prevent cell attachment of abrin. Further, internalization of the antibody bound to abrin was observed in cells by confocal microscopy. This is a novel finding which suggests that the antibody might function intracellularly and possibly explains the rescue of abrin's toxicity by the antibody in whole cells and animals. To our knowledge, this study is the first report on a neutralizing epitope for abrin and provides mechanistic insights into the poorly understood mode of action of anti-A chain antibodies against several toxins including ricin. PMID:23922965

Bagaria, Shradha; Ponnalagu, Devasena; Bisht, Shveta; Karande, Anjali A

2013-01-01

370

Mechanistic Insights into the Neutralization of Cytotoxic Abrin by the Monoclonal Antibody D6F10  

PubMed Central

Abrin, an A/B toxin obtained from the Abrus precatorius plant is extremely toxic and a potential bio-warfare agent. Till date there is no antidote or vaccine available against this toxin. The only known neutralizing monoclonal antibody against abrin, namely D6F10, has been shown to rescue the toxicity of abrin in cells as well as in mice. The present study focuses on mapping the epitopic region to understand the mechanism of neutralization of abrin by the antibody D6F10. Truncation and mutational analysis of abrin A chain revealed that the amino acids 74–123 of abrin A chain contain the core epitope and the residues Thr112, Gly114 and Arg118 are crucial for binding of the antibody. In silico analysis of the position of the mapped epitope indicated that it is present close to the active site cleft of abrin A chain. Thus, binding of the antibody near the active site blocks the enzymatic activity of abrin A chain, thereby rescuing inhibition of protein synthesis by the toxin in vitro. At 1?10 molar concentration of abrin:antibody, the antibody D6F10 rescued cells from abrin-mediated inhibition of protein synthesis but did not prevent cell attachment of abrin. Further, internalization of the antibody bound to abrin was observed in cells by confocal microscopy. This is a novel finding which suggests that the antibody might function intracellularly and possibly explains the rescue of abrin’s toxicity by the antibody in whole cells and animals. To our knowledge, this study is the first report on a neutralizing epitope for abrin and provides mechanistic insights into the poorly understood mode of action of anti-A chain antibodies against several toxins including ricin. PMID:23922965

Bagaria, Shradha; Ponnalagu, Devasena; Bisht, Shveta; Karande, Anjali A.

2013-01-01

371

Development of Anti-donor Antibody Directed Toward Non-MHC Antigens in Tolerant Animals  

PubMed Central

Background The clinical significance of antibodies directed against antigens other than MHC antigens is poorly understood and there are few large animal models in which such antibodies can be examined. We studied, both retrospectively and prospectively, the development of antibodies to non-MHC antigens in tolerant miniature swine. Methods Our database was assessed for cases of anti-donor antibody formation in tolerant animals over the last 20 years. Flow cytometry, absorption assays and familial analyses for inheritance pattern of the gene(s) potentially responsible for the antibody reactivities were carried out and an animal determined to be negative for this reactivity was immunized by a skin graft and subcutaneous injections of PBMCs from an antigen-positive donor. Results Sixteen of 469 tolerant animals tested were found to have developed anti-donor antibodies. These antibodies were found to be specific for the same, presumably single, non-MHC antigen. Familial analyses indicated that the gene encoding this antigen was expressed in an autosomal dominant manner in approximately 95% of the herd. In a prospective study, anti-donor antibodies with the same specificity as those observed retrospectively were successfully induced in an antigen-negative animal after immunization with PBMCs. Conclusions To our knowledge, this is the first report of the development of antibodies to a highly prevalent, non-MHC antigen present on peripheral blood mononuclear cells and developing in tolerant animals without signs of graft dysfunction. Considering the concern often raised by the appearance of anti-donor antibodies in transplant recipients, these data could have important implications for clinical transplantation. PMID:24933456

Scalea, Joseph R.; Villani, Vincenzo; Gillon, Bradford C.; Weiner, Joshua; Gianello, Pierre; Turcotte, Nicole; Arn, J. Scott; Yamada, Kazuhiko; Sachs, David H.

2014-01-01

372

Thrombotic microangiopathic haemolytic anaemia and antiphospholipid antibodies  

PubMed Central

Objective: To analyse the clinical and laboratory features of patients with thrombotic microangiopathic haemolytic anaemia (TMHA) associated with antiphospholipid antibodies (aPL). Methods: A computer assisted (PubMed) search of the literature was performed to identify all cases of TMHA associated with aPL from 1983 to December 2002. Results: 46 patients (36 female) with a mean (SD) age at presentation of TMHA of 34 (15) years were reviewed. Twenty eight (61%) patients had primary antiphospholipid syndrome (APS). TMHA was the first clinical manifestation of APS in 26 (57%) patients. The clinical presentations were haemolytic-uraemic syndrome (26%), catastrophic APS (23%), acute renal failure (15%), malignant hypertension (13%), thrombotic thrombocytopenic purpura (13%), and HELLP (haemolysis, elevated liver enzymes, and low platelet count in association with eclampsia) syndrome (4%). Lupus anticoagulant was detected in 86% of the episodes of TMHA, and positive anticardiolipin antibodies titres in 89%. Steroids were the most common treatment (69% of episodes), followed by plasma exchange (PE) (62%), anticoagulant or antithrombotic agents (48%), immunosuppressive agents (29%), and immunoglobulins (12%). Recovery occurred in only 10/29 (34%) episodes treated with steroids, and in 19/27 (70%) episodes treated with PE. Death occurred in 10/46 (22%) patients. Conclusions: The results emphasise the need for systematic screening for aPL in all patients with clinical and laboratory features of TMHA. The existence of TMHA in association with an APS forces one to rule out the presence of the catastrophic variant of this syndrome. PE is indicated as a first line of treatment for all patients with TMHA associated with aPL. PMID:15140782

Espinosa, G; Bucciarelli, S; Cervera, R; Lozano, M; Reverter, J; de la Red, G; Gil, V; Ingelmo, M; Font, J; Asherson, R

2004-01-01

373

For anti-HLA-specific donor antibodies detection by flow cytometry cytotoxic crossmatches comparison of methods.  

PubMed

Anti-HLA-specific donor antibodies induce rapid, irreversible destruction of the transplant (hyperacute rejection) that today happens rarely due to immunologic studies-prospective crossmatch-of patients awaiting the kidney graft. The usual approach for pretransplant donor/recipient evaluation is based on 2 methods: (1) the cytotoxic complement crossmatch (CDC) and (2) the flow cytometric crossmatch (FCX). The CDC crossmatch is positive when complement-fixing antibodies are present, an absolute contraindication to kidney transplantation. The more sensitive FCX-positive crossmatch detects low concentrations of unable to fix performed antibodies complement. It is an "index" of possible damage due to accelerated rejection. The target of our study was to develop a cytotoxic flow cytometry crossmatch (cFCX) that detected cytotoxic antibodies move sensitively than the traditional CDC method and also was less subjective and more standardized for interpretation studying sera from 23 patients; the cFCX showed the requested efficiency characteristics even in an emergency. In addition, the new method permited one to calculate a cutoff for positivity (average value of the negative control + 2 standard deviations), assuring an "objective" interpretation of the results that agreed with the CDC but was more sensitive and accurate allowing solution of ambiguous results for cases of "doubt"-positive CDC crossmatch. Furthermore, our aim was to correlate the effect of the strength of the anti-HLA antibodies determined by mean fluorescence intensity value of LabScreen Single Antigen beads with results of CDC, cFCX, and FCX methods. PMID:24034042

Cervelli, C; Pisani, F; Aureli, A; Azzarone, R; Scimitarra, M; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Famulari, A; Papola, F

2013-09-01

374

Rubella antibodies detected by several commercial immunoassays in hemagglutination inhibition-negative sera.  

PubMed Central

Although a very good correlation was found between the level of rubella antibodies measured by a standard hemagglutination inhibition (HI) test and by an enzyme-linked immunosorbent assay (ELISA) procedure (Cordia R), an appreciable proportion (31%) of ELISA-positive specimens were encountered among HI-negative sera. The reverse was rarely seen. Many of the HI-negative, ELISA-positive sera were also found to be positive for rubella antibodies by one or more other assay methods, including an immunofluorescence assay (IFA) procedure (FIAX), passive hemagglutination (PHA) (Rubacell and PHAST), latex agglutination (Rubascan), and a second ELISA procedure (Rubelisa). The specificity of all of the ELISA-positive HI-negative specimens was substantiated by absorption experiments. In these tests, the ELISA reactivities were blocked by rubella antigens, but not by a variety of tissue culture control antigens or by influenza virus grown on the same cell line. The findings indicate that many of the newer methods available for rubella antibody detection are more sensitive than HI for detecting low levels of rubella antibodies. Until more clinical information is available concerning the protective nature of these low levels of antibody, caution should be exercised in assessing the significance of these results. PMID:6643666

Kleeman, K T; Kiefer, D J; Halbert, S P

1983-01-01

375

Leptospirosis in beef herds from western Canada: Serum antibody titers and vaccination practices  

PubMed Central

One study described the frequency of pre-breeding vaccination for leptospirosis in 205 cow-calf herds from across western Canada and the prevalence of positive Leptospira antibody titers in unvaccinated, weaned calves from 61 of these herds. The percentages of herds vaccinated for leptospirosis were 13.7% in 2001 and 8.4% in 2002. Of 1539 calves examined, 13 (0.8%) had a positive antibody titer for a Leptospira serovar; the most common serovar detected was hardjo. A second study examined the prevalence of positive Leptospira antibody titers during the summer grazing season in 313 vaccinated and 478 unvaccinated cows from 40 cow-calf herds in southern Saskatchewan. Antibody titers for 7 Leptospira serovars were measured during the grazing season. Of the non-vaccinated cows, 9.6% were positive in the spring for serovar pomona, 6.7% for serovar grippotyphosa, and 6.1% for serovar icterohaemorrhagiae; the corresponding percentages for the fall were 5.5%, 3.0%, and 1.3%, respectively. Of 781 vaccinated and unvaccinated cows that were sampled twice, 11.3% of vaccinated cows and 2.3% of unvaccinated cows had increases in Leptospira antibody titers during the grazing season. PMID:22131577

Van De Weyer, Leanne M.; Hendrick, Steve; Rosengren, Leigh; Waldner, Cheryl L.

2011-01-01

376

Radiolabeling antibodies with holmium-166.  

PubMed

We report the preliminary results from radiolabeling of a chelate-conjugated antibody with 166Ho produced from the beta(-)-decay of 166Dy. Ho-166 was separated from mg quantities of Dy target by reverse phase ion-exchange chromatography employing a cation exchange HPLC column and 0.085 M alpha-HIBA at pH = 4.3 as eluent. Evaporation to dryness of 166Ho fraction (up to 25 mL) and thermal decomposition of alpha-HIBA yielded 166Ho in a dry state which was then solubilized in 0.5 mL of 0.1 M HCl. Subsequent radiolabeling of CHX-B-DTPA conjugated 135-14 monoclonal antibodies with purified 166 Ho was readily achieved with approximately 80% efficiency and with a specific activity of 3-4 mCi of 166Ho per mg of protein. 166Ho-antibody conjugates are stable with regards to transferrin challenge for a period of 50 h. Further, it was shown that any Fe3+ ions present in alpha-HIBA as an impurity interfere with the labeling. PMID:9106989

Dadachova, E; Mirzadeh, S; Smith, S V; Knapp, F F; Hetherington, E L

1997-04-01

377

Single-Chain Antibody Library  

DOE Data Explorer

Researchers at Pacific Northwest National Laboratory (PNNL) have constructed a nonimmune library consisting of 109 human antibody scFv fragments, which have been cloned and expressed on the surface of yeast. Nanomolar-affinity scFvs are routinely obtained by magnetic bead screening and flow cytometric sorting. The yeast library can be amplified 1010 fold without measurable loss of clonal diversity. This allows for indefinite expansion of the library. All scFv clones can be assessed directly on the yeast cell surface by immunofluorescent labeling and flow cytometry, obviating separate subcloning, expression, and purification steps. The ability to use multiplex library screening demonstrates the utility of this approach for high-throughput antibody isolation for proteomic applications. The yeast library may be used for research projects or teaching performed for U.S. Government purposes only. If you would like to request an aliquot of the single-chain antibody library for your research, please print and fill out the Materials Transfer Agreement (MTA) [PDF, 20K]. The website provides the contact information for mailing the MTA. [copied from http://www.sysbio.org/dataresources/singlechain.stm

Baird, Cheryl

378

Improved monoclonal antibodies to halodeoxyuridine  

DOEpatents

The development, method of production, characterization and methods of use of two hybridomas, CIdU-1 (ATCC Accession No. HB-8321) and CIdU-2 (ATCC Accession No. HB-8320), are described. These secrete IgG/sub 1/(K) immunoglobulins that react with halodeoxyuridine (HdU or halodU) such as bromo, chloro, fluoro and iodo deoxyuridine (BrdU, CldU, FdU and IdU), whether these are free in solution or incorporated into single stranded DNA in whole cells. The antibodies do not react with naturally occurring free nucleic acids or with deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) polymers. These antibodies are suitable for use in enzyme immunoassays for free CldU, FdU, IdU and BrdU and for detecting cells with these nucleotides incorporated into them. The monoclonal antibodies are useful in the detection of the sensitivity of tumor cells to specific chemotherapeutic agents, in the measurement of the rate of cellular DNA synthesis, in the measurement of the rate of proliferation of normal and malignant cells and in the detection of HPRT deficiency in cells. 1 tab.

Vanderlaan, M.; Dolbeare, F.A.; Gray, J.W.; Thomas, C.B.

1983-10-18

379

Detection of antibodies to HIV-1 in serum and saliva.  

PubMed

In this study we report the detection of antibodies to HIV-1 in paired serum and saliva collected from 118 HIV-1 infected patients and 80 normal controls in Madras, South India. Saliva was collected using Omnisal (R) collection device. All the reactive samples were confirmed by Western blot test (WB), while all the control serum and saliva were negative for HIV-1 antibodies. 107 (90.6%) HIV individual's serum and saliva contained antibodies to HIV-1. When these reactive samples were tested by WB test for confirmation the following results were obtained; 68% HIV individuals' paired serum and saliva were positive; while 9% of serum samples were positive and the saliva specimens were negative on WB. 3% of paired samples showed indeterminate Western blot pattern in contrast to 10% of serum showed full WB pattern while the saliva result was indeterminate. It is suggested that saliva testing may be appropriate for surveillance and epidemiological studies. However, if used for individual HIV diagnosis it is imperative to use a confirmatory test. PMID:12521084

Samuel, N M; Chandrasekaran, A; Paul, S A

1997-04-01

380

Epitope Mapping of Antibodies to Alpha-Synuclein in LRRK2 Mutation Carriers, Idiopathic Parkinson Disease Patients, and Healthy Controls  

PubMed Central

Alpha-synuclein (Snca) plays a major role in Parkinson disease (PD). Circulating anti-Snca antibodies has been described in PD patients and healthy controls, but they have been poorly characterized. This study was designed to assess the prevalence of anti-Snca reactivity in human subjects carrying the LRRK2 mutation, idiopathic PD (iPD) patients, and healthy controls and to map the epitopes of the anti-Snca antibodies. Antibodies to Snca were detected by ELISA and immunoblotting using purified recombinant Snca in plasma from individuals carrying LRRK2 mutations (104), iPD patients (59), and healthy controls (83). Epitopes of antibodies were mapped using recombinant protein constructs comprising different regions of Snca. Clear positive anti-Snca reactivity showed no correlation with age, sex, years of evolution, or the disability scores for PD patients and anti-Snca reactivity was not prevalent in human patients with other neurological or autoimmune diseases. Thirteen of the positive individuals were carriers of LRRK2 mutations either non-manifesting (8 out 49 screened) or manifesting (5 positive out 55), three positive (out of 59) were iPD patients, and five positive (out of 83) were healthy controls. Epitope mapping showed that antibodies against the N-terminal (a.a. 1–60) or C-terminal (a.a. 109–140) regions of Snca predominate in LRRK2 mutation carriers and iPD patients, being N122 a critical amino acid for recognition by the anti-C-terminal directed antibodies. Anti-Snca circulating antibodies seem to cluster within families carrying the LRRK2 mutation indicating possible genetic or common environmental factors in the generation of anti-Snca antibodies. These results suggest that case-controls’ studies are insufficient and further studies in family cohorts of patients and healthy controls should be undertaken, to progress in the understanding of the possible relationship of anti-Snca antibodies and PD pathology. PMID:25076905

Alvarez-Castelao, Beatriz; Gorostidi, Ana; Ruíz-Martínez, Javier; López de Munain, Adolfo; Castaño, José G.

2014-01-01

381

Generation of monospecific antibodies based on affinity capture of polyclonal antibodies.  

PubMed

A method is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. Polyclonal antibodies directed towards four proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers, were selected and antibodies to several non-overlapping epitopes were generated and subsequently validated by Western blot, immunohistochemistry, and immunofluorescence. For all four proteins, a dramatic difference in functionality could be observed for these monospecific antibodies directed to the different epitopes. In each case, at least one antibody was obtained with full functionality across all applications, while other epitope-specific fractions showed no or little functionality. These results present a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies, providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies. PMID:21898641

Hjelm, Barbara; Forsström, Björn; Igel, Ulrika; Johannesson, Henrik; Stadler, Charlotte; Lundberg, Emma; Ponten, Fredrik; Sjöberg, Anna; Rockberg, Johan; Schwenk, Jochen M; Nilsson, Peter; Johansson, Christine; Uhlén, Mathias

2011-11-01

382

Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations  

PubMed Central

Background: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera. Objective: To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations. Methods: Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA. Results: In population 1, we defined adapted cut offs corresponding to a specificity of ?98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations. Conclusion: A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies. PMID:15547083

De Rycke, L; Peene, I; Hoffman, I; Kruithof, E; Union, A; Meheus, L; Lebeer, K; Wyns, B; Vincent, C; Mielants, H; Boullart, L; Serre, G; Veys, E; De Keyser, F

2004-01-01

383

Antibodies reactive to Ehrlichia spp. Are common in Oklahoma horses.  

PubMed

Abstract Tick infestations and infection with tick-borne agents are commonly recognized in horses in North America, but equine infection with true Ehrlichia spp. has not been described. To determine the degree to which horses in the south-central United States are naturally exposed to and infected with tick-borne disease agents, serum samples were collected at random (n=240) or from horses with active tick infestations (n=73) and tested by immunofluorescence antibody assay (IFA) and/or enzyme-linked immunosorbent assay (ELISA) for evidence of antibodies reactive to Ehrlichia spp., Anaplasma spp., and Borrelia burgdorferi. Positive samples were further evaluated by species-specific serology for antibodies reactive to E. canis and E. chaffeensis, and whole blood samples were tested by PCR for evidence of infection with E. canis, E. chaffeensis, E. ewingii, and an E. ruminantium-like organism referred to as the Panola Mountain Ehrlichia. Antibodies reactive to Ehrlichia spp. were identified in 8.75% (21/240) of the randomly acquired samples and 24.7% (18/73) of the serum samples from tick-infested horses, but species-specific ELISA and PCR failed to confirm exposure to or infection with any known Ehrlichia spp. Antibodies to Anaplasma spp. (5/313; 1.6%) and B. burgdorferi (3/313; 1.0%) were uncommon. These data suggest that horses in the south-central United States are likely exposed to a novel Ehrlichia sp. Further research is needed to identify the etiologic agent responsible for the serologic activity seen and to determine the clinical significance, if any, of this finding. PMID:25072984

Carmichael, Robert C; Duell, Jason R; Holbrook, Todd C; Herrin, Brian H; Leutenegger, Christian M; O'Connor, Thomas P; Little, Susan E

2014-08-01

384

Antibody-drug conjugate (ADC) clinical pipeline: a review.  

PubMed

Biological therapies play an increasing role in cancer treatment, although the number of naked antibodies showing clinical efficacy as single agent remains limited. One way to enhance therapeutic potential of antibodies is to conjugate them to small molecule drugs. This combination is expected to bring together the benefits of highly potent drugs on the one hand and selective binders of specific tumor antigens on the other hand. However, designing an ADC is more complex than a simple meccano game, requiring thoughtful combination of antibody, linker, and drugs in the context of a target and a defined cancer indication. Lessons learned from the first-generation antibody-drug conjugate (ADC) and improvement of the technology guided the design of improved compounds which are now in clinical trials. Brentuximab vedotin (Adcetris(®)), an anti-CD30 antibody conjugated to a potent microtubule inhibitor for the treatment of Hodgkin's lymphoma and anaplastic large cell lymphomas, is the only marketed ADC today. A total of 27 ADC are currently undergoing clinical trials in both hematological malignancies and solid tumor indications. Among them, T-DM1 (trastuzumab emtansine), an ADC comprised of trastuzumab conjugated to DM1, via a non-cleavable linker, is showing very promising results in phase III for the treatment of HER2-positive refractory/relapsed metastatic breast cancer. Other compounds, such as CMC-544, SAR3419, CDX-011, PSMA-ADC, BT-062, and IMGN901 currently in clinical trials, targeting varied antigens and bearing different linker and drugs, contribute to the learning curve of ADC, as do the discontinued ADC. Current challenges include improvement of the therapeutic index, linked to a careful selection of the targets, a better understanding of ADC mechanism of action, the management and understanding of ADC off-target toxicities, as well as the selection of appropriate clinical settings (patient selection, dosing regimen) where these molecules can bring highest clinical benefit. PMID:23913138

Sassoon, Ingrid; Blanc, Véronique

2013-01-01

385

An immunohistological study of testicular germ cell tumours using two different monoclonal antibodies against placental alkaline phosphatase.  

PubMed Central

Using two monoclonal antibodies directed against placental alkaline phosphatase (H17E2 and D20L) the immunohistological staining of testicular germ cell tumours was compared with that of a wide range of normal and malignant tissues. All seminomas and malignant teratomas tested gave strong positive labelling with H17E2 but were either negative or only patchily positive with D20L. Neither antibody gave any positive reaction on the normal tissues tested. All other malignancies were negative with both antibodies apart from two cases of ovarian and one case of endometrical cancer (strongly stained by H17E2) and three cases of colonic carcinoma (weakly and patchily stained by both H17E2 and D20L). This indicates that germ cell neoplasms generally express a form of placental alkaline phosphatase recognised by antibody H17E2. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:6362705

Epenetos, A. A.; Travers, P.; Gatter, K. C.; Oliver, R. D.; Mason, D. Y.; Bodmer, W. F.

1984-01-01

386

Prevalence of IgG antibodies to Ebola virus in individuals during an Ebola outbreak, Democratic Republic of the Congo, 1995.  

PubMed

During the 1995 outbreak of Ebola (EBO) hemorrhagic fever in Kikwit, Democratic Republic of Congo, two surveys using a new ELISA for EBO (subtype Zaire) virus antigen were conducted to assess the prevalence of EBO IgG antibodies among residents of Kikwit and the surrounding area. The first study determined the proportion of antibody-positive individuals who were self-identified forest and city workers from the Kikwit area. Serum samples from 9 (2.2%) of 414 workers had IgG EBO antibodies. The second study determined the proportion of EBO antibody-positive individuals who lived in villages surrounding Kikwit. The prevalence of IgG EBO antibodies in this population was 9.3% (151161). The difference in the overall prevalence of EBO antibodies may indicate that villagers have a greater chance of exposure to EBO virus compared with those living in and in close proximity to cities. PMID:9988172

Busico, K M; Marshall, K L; Ksiazek, T G; Roels, T H; Fleerackers, Y; Feldmann, H; Khan, A S; Peters, C J

1999-02-01

387

ANTIBODY SYNTHESIS AT THE CELLULAR LEVEL  

PubMed Central

The specific suppressing activity of passively administered antibody on 7S antibody synthesis against sheep and chicken red blood cells has been investigated at the cellular level using the indirect hemolytic agar-plaque technique. 7S antibody production was found to be sensitive to antibody-induced suppression. No inhibitory effect of transferred antibody was seen until 48 to 72 hr after administration. This indicates that the action of antibody is not by direct suppression of synthesis of already committed cells but rather by removal from the system of the stimulus for maintenance of 7S synthesis. The sensitivity of the 7S system to inhibition decreases with time after immunization but significant specific suppression could still be obtained if transfer of antibody was delayed until 40 days after immunization. The present findings emphasize the role of antibody as a feedback factor during a substantial postpeak period of 7S antibody synthesis and suggest an important role of antigen in stab