Autoantibodies

Objective.To report baseline and followup data on the first 438 patients with systemic sclerosis (SSc) included in the Belgian Systemic Sclerosis Cohort.Methods.According to LeRoy and Medsger’s classification, 73 patients with limited SSc (lSSc), 279 with limited cutaneous SSc (lcSSc), and 86 with diffuse cutaneous SSc (dcSSc) were included. History was collected and clinical examination, blood tests, and paraclinical investigations were repeated. The Disease Activity Score (DAS) and Disease Severity Score (DSS) of several organ systems were computed. An organ system was considered to demonstrate SSc if the corresponding DSS was ≥ 1.Results.At baseline, patients with dcSSc had more general, joint/tendon, muscle, gastrointestinal, and kidney involvement. Mean DLCO was below normal in patients with lSSc, indicating unsuspected lung involvement. Patients with anti-Scl-70 had more vascular, skin, joint/tendon, and lung involvement. Patients with anti-RNA polymerase III had more skin and...

Various adsorption techniques are available to remove serum autoantibodies and subsequently detect the underlying alloantibody in previously transfused patients with autoimmune haemolytic anaemia. We planned to establish a suitable adsorption technique in our transfusion service which can remove all autoantibodies and detect underlying alloantibodies rapidly, cheaply and effectively. We evaluated 71 direct antiglobulin test-reactive patients with warm AIHA over a period of 20 months. Twenty-three of these 71 patients who had a previous history of blood transfusion or pregnancy and were confirmed carriers of autoantibodies (indirect antiglobulin test-reactive) were considered for the adsorption study. Depending on the adequacy of samples, history of blood transfusion and severity of anaemia either autoadsorption or alloadsorption or both using polyethylene glycol (PEG) or low ionic strength saline (LISS)-papain were performed. Underlying alloantibodies were detected in 7 of the 23 pa...

A complement fixing autoantibody reacting with certain renal collecting duct cells, possibly so called dark cells, is described in 113 patients. Clinically, the antibody was strongly associated with thyroid disorders and pernicious anaemia. The patients also showed a markedly increased frequency of thyroid antibodies and antibodies to gastric parietal cells and to intrinsic factor. One of the patients had a distal renal tubular acidosis (RTA) and pernicious anaemia. The antibody was also found in all of three other patients with either latent or manifest RTA. RTA is associated with various immunological diseases, and the renal collecting duct cell antibody may turn out to be a marker of this disorder, either involved in its pathogenesis or representing a secondary phenomenon.

Autoantibodies neutralizing human ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type 1 motif), the metalloprotease that physiologically cleaves von Willebrand factor, are a major cause of severe deficiency of the protease and of acquired thrombotic ...

Pemphigus is a group of potentially life-threatening diseases characterized by cutaneous and mucosal blistering. There is a fairly strong genetic background to pemphigus with linkage to HLA class II alleles. Certain ethnic groups, such as Ashkenazi Jews and those of Mediterranean origin, are especially liable to pemphigus. Pemphigus vulgaris (PV), the most common and important variant, is an autoimmune blistering disease characterized by circulating pathogenic IgG antibodies against desmoglein 3 (Dsg3), about half the patients also having Dsg1 autoantibodies. Oral lesions are initially vesiculobullous but readily rupture, new bullae developing as the older ones rupture and ulcerate. Biopsy of perilesional tissue, with histological and immunostaining examinations, is essential to the diagnosis. Serum autoantibodies to either Dsg1 or Dsg3 are best detected by both normal human skin and monkey esophagus or by enzyme-linked immunosorbent assay (ELISA). Before the introduction of cortico...

The pathophysiology of exocrine dysfunction observed in Sjögren's syndrome (SS) is not fully understood. The purpose of this study was to investigate whether autoan-tibodies against human AQP5 are present in the sera of SS patients. Frozen sections of mouse submandibular salivary glands, CHO cells over-expressing a human AQP5–GFP fusion protein or GFP, and MDCK cells over-expressing AQP5 were used in the indirect immunofluorescence assay to detect anti-AQP5 autoantibodies in the sera from patients with primary SS. The lysates of HEK-293 cells over-expressing the AQP5–GFP fusion protein or GFP were used for immuno-precipitation. Serum IgG from the SS patients but not from the control subjects stained acinar cells in the mouse salivary glands, the signals of which colocalized with those of AQP5-specific antibodies. Serum IgG from the SS patients also selectively stained AQP5–GFP expressed in CHO cells. However, both the control and SS sera immunoprecipitated the AQP5–GFP, suggesting that autoantibodies against AQP5 were also present in the control sera. The screening of 53 control and 112 SS samples by indirect immunofluorescence assay using the AQP5-expressing MDCK cells revealed the presence of significantly higher levels of anti-AQP5 IgG in the SS samples than in the control samples with sensitivity of 0.73 and a specificity of 0.68. Furthermore, the presence of anti-AQP5 autoantibodies was associated with low resting salivary flow in SS patients. In conclusion, anti-AQP5 autoantibodies were detected in the sera from SS patients, which could be a novel biomarker of SS and provide new insight into the pathogenesis of SS.

OBJECTIVES To establish the frequency of auto-antibodies anti-HSP 70 using ELISA and Western Blot (WB) methods and to compare the results of each method among patients with the Ménière's Disease (MD) and internal ear diseases (IED) who do not fulfill criteria for MD. Sensibility, specificity and predictive values of anti-HSP70 test in diagnosis of MD were calculated. STUDY Prospective, case-control. METHODS Blood samples were collected from 31 patients with MD and 78 patients with non Ménière IED. Data regarding cochlear and vestibular symptoms were obtained and blood sample was tested. RESULTS ELISA tests results were positive in 4(13%) patients and results of WB were positive in 8(26%) patients. Among patients with positive ELISA results, 1 patient presented active disease and in the remaining 3 patients the disease was inactive. Among the 8 WB positive patients, only 2 patients presented active disease. Statistical analyses did not establish any association between serologic ...

To determine celiac disease (CD) prevalence and associated manifestations or risk factors in healthy adult Emiratis. It is a cross-sectional prospective study, recruiting 1197 (573 women and 624 men) healthy Emiratis between September 2007 and April 2008 among those who went to Al Ain Hospital to undertake the prenuptial examination. Test for anti-tissue transglutaminase (tTG) IgA antibodies was used for CD diagnosis. Subjects with positive results in the anti tTG antibodies assay were also tested for anti-endomysial (EMA) IgA antibodies. A structured interview was used to collect basic demographic and clinical recall data including: information on name, contact address, age, gender, education status, previous diagnosis of CD, diagnosis of CD in 1(st) degree relatives and history of "chronic diarrhea, anemia, headache, hepatitis, diabetes, tumor, and thyroid disorder". Fourteen blood samples (1.17%; 14/1197) were seropositive for CD. The latent CD seropositive patients wer...

Susceptibility to systemic lupus erythematosus (SLE) is associated with genetic, hormonal, immunological, and environmental factors. Many genes have been related with the appearance of SLE, including several loci that code different complement components and their receptors. Some genetic deficiencies of complement molecules are strongly associated with SLE, probably because these deficiencies could cause decreased clearance of apoptotic cell material. As a consequence of the apoptotic material accumulation, high levels of autoantigens can be presented inappropriately to the immune system in an inflammatory context, resulting in an imbalance on the mechanisms of immunological tolerance, immune system activation, and autoantibody production. Recent studies proposed a role to the mannose-binding lectin (MBL) in the SLE physiopathogenesis. This protein activates the complement system, and the presence of several polymorphisms at the promoter and coding regions of the MBL-2 gene determines alterations at the plasma levels of MBL. Some of these polymorphisms have been associated with SLE susceptibility, as well as with clinical and laboratory typical features of this disease, cardiovascular events, and infections. Besides, it has been described that the presence of anti-MBL autoantibodies in sera of SLE patients can influence MBL plasma levels and its functional activity.

Abstract: There is strong evidence that non-immune chronic idiopathic neutropenia of adult is a cytokine-mediated syndrome characterized by (a) neutropenia of varying degree associated with a low number of lineage-specific CD34+ cells and increased production of inhibitors of hematopoiesis, including transforming growth factor-β1 and tumor necrosis factor-α; (b) lymphopenia due to selective loss of primed/memory T-cells and NK cells; (c) increased splenic volume on ultrasonography in 48.1% of patients; (d) osteopenia and/or osteoporosis in 60.0% of patients; (e) anemia, mostly of the type of anemia of chronic disease, in 15.6% of patients; (f) features of chronic antigenic stimulation, including increased proportion of bone marrow plasma cells, increased serum levels of IgG1 and/or IgA, increased frequency of monoclonal gammopathy of undetermined significance, increased frequency of antinuclear antibodies with specific reactivity, and increased serum levels of circulating immune complexes; and (g) increased concentrations of a variety of macrophage-derived pro-inflammatory cytokines and chemokines capable of affecting bone metabolism, bone marrow function, and leukocyte trafficking. All these findings are suggestive of the existence of an unrecognized low-grade chronic inflammatory process which may be involved in the pathogenesis of the disorder. Neutropenia in these patients is probably the result of a combination of at least three factors, reduced neutrophil production in bone marrow, enhanced neutrophil extravasation, and increased sequestration and/or extravasation of neutrophils into the spleen.

We analyzed our historic patient database at North Shore University Hospital and determined both the overall frequency of anti-Js(a) and the frequency at which it was detected in combination with other alloantibodies to red blood cell (RBC) antigens. Screening cells used currently are negative for Js(a). Our data suggest that anti-Js(a) would not be detected in 30 to 40 percent of patients in which it is the sole antibody present. Since 1996 the antibody was only detected when other antibodies were found in the screening process. We are exposing 1.7 percent of our patients (90 patients/year) to Js(a). The clinical significance of anti-Js(a) is apparent with previous literature, and our conclusion is that additional studies should be performed to determine whether Js(a) should be included in current antibody screening cells.

We investigated sera from elderly subjects with and without age-related macular degeneration (AMD) for presence of autoantibodies (AAbs) against human macular antigens and characterized their identity. Sera were collected from participants in the Age-Related Maculopathy Ancillary (ARMA) Study, a cross-sectional investigation ancillary to the Health ABC Study, enriched with participants from the general population. The resulting sample (mean age: 79.2±3.9 years old) included subjects with early to advanced AMD (n = 131) and controls (n = 231). Sera were tested by Western blots for immunoreactive bands against human donor macular tissue homogenates. Immunoreactive bands were identified and graded, and odds ratios (OR) calculated. Based on these findings, sera were immunoprecipitated, and subjected to 2D gel electrophoresis (GE). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify the targets recognized by circulating AAbs seen on 2D-GE, followed by ELISAs wi...

PRKDC encodes for DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a kinase that forms part of a complex (DNA-dependent protein kinase [DNA-PK]) crucial for DNA double-strand break repair and V(D)J recombination. In mice DNA-PK also interacts with the transcription factor autoimmune regulator (AIRE) to promote central T-cell tolerance. We sought to understand the causes of an inflammatory disease with granuloma and autoimmunity associated with decreasing T- and B-cell counts over time that had been diagnosed in 2 unrelated patients. Genetic, molecular, and functional analyses were performed to characterize an inflammatory disease evocative of a combined immunodeficiency. We identified PRKDC mutations in both patients. These patients exhibited a defect in DNA double-strand break repair and V(D)J recombination. Whole-blood mRNA analysis revealed a strong interferon signature. On activation, memory T cells displayed a skewed cytokine response typical of TH2 and TH1 but not TH...