Autoantibodies In Individuals Research Articles

Prevalence of Autoantibodies in patients with Hereditary Alpha Tryptasemia.

Hereditary alpha-tryptasemia (HT) is associated with postural orthostatic tachycardic syndrome (POTS), hypermobile Ehlers Danlos Syndrome (hEDS), and mast cell activation syndrome (MCAS). While POTS, hEDS and MCAS have all demonstrated increased prevalence of autoimmunity, this has not been investigated in HT populations. Our objective was to describe the prevalence of autoantibodies in individuals with HT. We retrospectively studied a cohort of patients with positive genotyping for HT at a tertiary care allergy clinic. Demographic data including previous autoimmune history and autoantibody serologies were extracted on chart review. A literature search was conducted to determine the prevalence of specific autoimmune and autoantibody prevalences in the general population. We compared the proportions of autoantibody positivity and established autoimmune diseases in our cohort of HT individuals against those in general populations. We identified 101 patients with HT. Median age was 43 years (range 15-75) and most were female (87/101; 86.1%). Prevalence of self-reported drug hypersensitivity was 52/101 (52.5%) patients. The proportion of individuals with HT with positive tTG antibody (3/61, 4.9%) was significantly higher than that reported in the general population (133/16667, 0.8%) (p<0.001). The prevalence of SLE (1/101, 1%) and celiac disease (5/101, 5%) in our cohort were found to be significantly higher than the prevalence in the general population [194/96996, 0.2% (p=0.035) and 26/2845, 0.9% (p<0.001), respectively]. Patients with HT have increased prevalence of celiac disease, SLE and positive anti-tTG serology as well as self-reported drug hypersensitivity, relative to general populations.

KIR2DL5+CD8+ T cells associate with dietary lipid intake and are active in type 1 diabetes

BackgroundRecent studies have shown that KIR+CD8+ T cells play a role in suppressing autoimmunity by eliminating pathogenic CD4+ T cells. However, their specific role in type 1 diabetes (T1D) remains unclear. MethodsIn this study, we enrolled 108 patients diagnosed with T1D and 86 healthy individuals. We conducted flow cytometric analysis to examine the various subtypes of KIR+CD8+ T cells derived from peripheral blood mononuclear cells. Additionally, CD8+ T cells were isolated from the peripheral blood of T1D patients to assess the functions of different KIR+CD8+ T cell subtypes. To investigate the influence of lipids on the characteristics and activities of these T cell subtypes, the isolated CD8+ T cells were cultured with varying concentrations of palmitic acid (PA). Furthermore, we utilized an NSG (NOD scid gamma) mouse adoptive transfer model to assess the impact of dietary lipid intake on the functionality of KIR2DL5+CD8+ T cells in vivo. ResultsWe observed variations in circulating KIR+CD8+ T cell subtypes between patients with T1D and healthy controls. Notably, we observed a significant negative correlation between the frequencies of circulating KIR+CD8+ T cells and the titers of ZnT8 autoantibodies in individuals with T1D. Among these subtypes, KIR2DL5+CD8+ T cells demonstrated a positive association with dietary fat intake, characterized by increased perforin expression and reduced PD-1 expression. Importantly, KIR2DL5+CD8+ T cells exhibited enhanced proliferative capacity compared to other KIR+CD8+ T cell subsets. Palmitic acid (PA) was found to enhance the activation of KIR2DL5+CD8+ T cells and strengthened their ability to suppress CD4+ T cell proliferation in T1D patients. Moreover, dietary lipid intake significantly enhanced the functionality of KIR2DL5+CD8+ T cells in an NSG mouse adoptive transfer model. ConclusionOur findings suggest that lipid intake enhances the functionality of human KIR2DL5+CD8+ T cells and may offer implications for immunotherapy in T1D.

The interlink between thyroid autoimmunity and type 1 diabetes and the impact on male and female fertility.

The aim of this review is to discuss the several interconnections between thyroid autoimmunity and type 1 diabetes in terms of epidemiology, immunoserology, genetic predisposition, and pathogenic mechanisms. We will also analyze the impact of these conditions on both male and female fertility. A literature search was carried out using the MEDLINE/PubMed, Scopus, Google Scholar, ResearchGate, and Clinical Trials Registry databases with a combination of keywords. It was found that the prevalence of thyroid autoantibodies in individuals with type 1 diabetes (T1DM) varied in different countries and ethnic groups from 7 to 35% in both sexes. There are several types of autoantibodies responsible for the immunoserological presentation of autoimmune thyroid diseases (AITDs) which can be either stimulating or inhibiting, which results in AITD being in the plus phase (thyrotoxicosis) or the minus phase (hypothyroidism). Different types of immune cells such as T cells, B cells, natural killer (NK) cells, antigen presenting cells (APCs), and other innate immune cells participate in the damage of the beta cells of the islets of Langerhans, which inevitably leads to T1D. Multiple genetic and environmental factors found in variable combinations are involved in the pathogenesis of AITD and T1D. In conclusion, although it is now well-known that both diabetes and thyroid diseases can affect fertility, only a few data are available on possible effects of autoimmune conditions. Recent findings nevertheless point to the importance of screening patients with immunologic infertility for AITDs and T1D, and vice versa.

Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis - a cohort study of 70 adult patients with myositis in a single center.

Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort. Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features. Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected. The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.

Role of IL-27 in Epstein-Barr virus infection revealed by IL-27RA deficiency.

Epstein-Barr virus (EBV) infection can engender severe B cell lymphoproliferative diseases1,2. The primary infection is often asymptomatic or causes infectious mononucleosis (IM), a self-limiting lymphoproliferative disorder3. Selective vulnerability to EBV has been reported in association with inherited mutations impairing T cell immunity to EBV4. Here we report biallelic loss-of-function variants in IL27RA that underlie an acute and severe primary EBV infection with a nevertheless favourable outcome requiring a minimal treatment. One mutant allele (rs201107107) was enriched in the Finnish population (minor allele frequency = 0.0068) and carried a high risk of severe infectious mononucleosis when homozygous. IL27RA encodes the IL-27 receptor alpha subunit5,6. In the absence of IL-27RA, phosphorylation of STAT1 and STAT3 by IL-27 is abolished in T cells. In in vitro studies, IL-27 exerts a synergistic effect on T-cell-receptor-dependent T cell proliferation7 that is deficient in cells from the patients, leading to impaired expansion of potent anti-EBV effector cytotoxic CD8+ T cells. IL-27 is produced by EBV-infected B lymphocytes and an IL-27RA-IL-27 autocrine loop is required for the maintenance of EBV-transformed B cells. This potentially explains the eventual favourable outcome of the EBV-induced viral disease in patients with IL-27RA deficiency. Furthermore, we identified neutralizing anti-IL-27 autoantibodies in most individuals who developed sporadic infectious mononucleosis and chronic EBV infection. These results demonstrate the critical role of IL-27RA-IL-27 in immunity to EBV, but also the hijacking of this defence by EBV to promote the expansion of infectedtransformed B cells.

Pancreatic autoantibodies in individuals with a clinical diagnosis of type 2 diabetes mellitus

Objectives: It can be challenging to accurately diagnose type 2 diabetes (T2D) in children based on clinical features alone. We aimed to describe pediatric patients with a clinical diagnosis of T2D who are positive for pancreatic autoantibodies and compare their clinical features to patients with T2D without autoantibodies. Material and Methods: This cross-sectional study and medical record review included patients aged 10–30 years with T2D seen at our pediatric diabetes clinic between January 01, 2013, and December 31, 2020. We compared the characteristics of autoantibody-positive patients with autoantibody-negative patients using Chi-square tests for binary variables and t-tests for continuous variables. Results: Eleven out of 87 (12.6%) patients with a clinical diagnosis of T2D had positive autoantibody results. The groups with and without antibodies were not significantly different in terms of age, sex, and body mass index (BMI) Z-score. However, the hemoglobin A1c (HbA1c) closest to the time of the first autoantibody test was significantly lower in the autoantibody-positive group. Two of the 11 antibody-positive patients had two positive autoantibodies and one had four positive autoantibodies. The other eight patients were positive for one autoantibody only. One of the 11 antibody-positive patients had an episode of diabetic ketoacidosis (DKA). Conclusion: While age, sex, and BMI were similar in both groups, patients with autoantibodies had significantly lower HbA1c at the time of antibody testing and one patient went into DKA. Autoantibodies should be measured in all patients diagnosed with diabetes to avoid the consequences of potential misclassification.

Prevalence of Positivity for Diabetes-Associated Autoantibodies in Individuals with Type 2 Diabetes and Their Further Characterisation: Cross-sectional Study from Slovakia.

Individuals initially diagnosed with type 2 diabetes (T2D) might exhibit positivity for diabetes-associated autoantibodies (DAA +). We investigated the prevalence of DAA positivity in a group of individuals with T2D who were referred to a tertiary diabetes centre within a pre-specified period of time. We aimed to identify characteristics linked with DAA positivity by comparing DAA + individuals with their DAA-negative counterparts. This was a cross-sectional study into which all T2D patients referred to the NationalInstitute of Endocrinology and Diabetology, Ľubochňa, Slovakia, between 1 January and 30 June 2016 were included. Data on > 70 participants' characteristics, including antibodies against glutamic acid decarboxylase (anti-GAD65), insulinoma-associated antigen IA-2 (IA-2A) and insulin (IAA), were collected. Six hundred and ninety-two individuals (387, 55.6% female) with a median (range) age of 62 (24-83) years, HbA1c of 8.9 (5.0-15.7)% [74 (31-148mmol/mol)] and diabetes duration of 13.0 (0-42) years were analysed. One hundred and forty-five (145/692, 21.0%) tested positive for at least one DAA; 136/692 (19.7%) were positive for anti-GAD65, 21/692 (3.0%) were positive for IA-2A and 9/692 (1.3%) were positive for IAA. Only 84.9% of the DAA + individuals aged > 30years at the time of diabetes diagnosis met the current diagnostic criteria for latent autoimmune diabetes of adults (LADA). DAA + differed from DAA- individuals in multiple characteristics, including the incidence of hypoglycaemia. Several pathological processes linked with distinct types of diabetes can develop in parallel, including insulin resistance and autoimmune insulitis. In this single-centre cross-sectional study from Slovakia, we report a higher than previously published prevalence of DAA positivity in agroup ofindividualswith a formal diagnosis of T2D.

190-LB: Differences in Postprandial and Counterregulatory Glucagon Excursions in Healthy Relatives to Type 1 Diabetes with Different Number of Islet Autoantibodies

Background and aims: Early changes in glucagon during the progression to type 1 diabetes (T1D) are not well understood. We investigate whether the glucagon responses to a mixed meal and hypoglycemia depend on the number of islet autoantibodies (Ab) in individuals at risk for T1D. Methods: Sixty healthy relatives of T1D with mean±SD age of 23.7±10.7 years, HbA1c of 5.3±0.3%, and BMI of 23.8±5.6 kg/m2 and zero (N=21), one (N=18), and ≥2 (N=21) Ab, were enrolled in an ancillary study from the NIH-funded TrialNet Pathway to Prevention study. Participants underwent a clinical test consisting of a mixed meal tolerance test (MMTT) followed by insulin-induced hypoglycemia. Glucagon was measured from -30 to 120 min around the MMTT and 0 to 40 min during hypoglycemia to estimate the Ab group differences in the meal and counter-regulatory glucagon responses assessed via the glucagon incremental area under the curve (iAUC). Results: There were significant differences in the net iAUC of the glucagon responses to the MMTT (p=0.024), while the group difference in the glucagon counter-regulation estimated via the total AUC approached significance (p=0.08). Conclusion: The study suggests that the glucagon responses to a meal and possibly, hypoglycemia, may be altered during the very early stages of the progression to T1D. Disclosure T. Igbe: None. E. Montaser: None. M. D. Breton: Consultant; Dexcom, Inc. Research Support; Dexcom, Inc. Consultant; Tandem Diabetes Care, Inc. Research Support; Tandem Diabetes Care, Inc., Novo Nordisk. Consultant; Roche Diabetes Care, Sanofi, Arecor. S. A. Brown: Research Support; Dexcom, Inc., Insulet Corporation, Tandem Diabetes Care, Inc. M. D. DeBoer: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. A. L. McCall: None. B. Kovatchev: Speaker's Bureau; Tandem Diabetes Care, Inc. Research Support; Dexcom, Inc., Novo Nordisk, Tandem Diabetes Care, Inc. Other Relationship; Dexcom, Inc., Johnson &amp; Johnson Medical Devices Companies, Novo Nordisk, Sanofi. L. Farhy: Research Support; Dexcom, Inc., Novo Nordisk. Funding National Institute of Diabetes and Digestive and Kidney Diseases (DP3DK106907); Commonwealth Research Commercialization Fund (MF20-007-LS); The Leona M. and Harry B. Helmsley Charitable Trust (2204-05134); JDRF (2-SRA-2022-1260-S-B)

Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.

The study of autoantibody isotypes in autoimmune diseases is useful for identifying clinically relevant endotypes. This study was undertaken to study the prevalence and clinical significance of different isotypes and IgG subclasses of anti-peptidylarginine deiminase 4 (anti-PAD4) autoantibodies in individuals with rheumatoid arthritis (RA). In 196 RA subjects and 64 healthy controls, anti-PAD4 antibody types were determined using enzyme-linked immunosorbent assay. We investigated associations between anti-PAD4 antibodies and clinical outcomes, and relevant features were confirmed in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG2, anti-PAD4 IgG3, anti-PAD4 IgG4, anti-PAD4 IgA, and anti-PAD4 IgE antibodies were more frequent in RA patients than healthy controls (P < 0.001). Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE were associated with distinct clinical features. Anti-PAD4 IgG1 was predictive of progressive radiographic joint damage (odds ratio [OR] 4.88, P=0.005), especially in RA patients without baseline joint damage (40% versus 0%, P=0.003) or in those negative for anti-cyclic citrullinated peptide and/or rheumatoid factor (OR 32; P=0.009). IgG1 was also associated with higher levels of C-reactive protein (P=0.006) and interleukin-6 (P=0.021). RA patients with anti-PAD4 IgG3 had higher baseline joint damage scores (median Sharp/van der Heijde score 13 versus 7, P=0.046), while those with anti-PAD4 IgE had higher Disease Activity Score in 28 joints (median 4.0 versus 3.5, P=0.025), more frequent rheumatoid nodules (31% versus 16%, P=0.025), and more frequent interstitial lung disease (ground-glass opacification) (24% versus 9%, P=0.014). Anti-PAD4 IgG1 antibody associations with joint damage were corroborated in an independent RA cohort. Anti-PAD4 IgG1, anti-PAD4 IgG3, and anti-PAD4 IgE antibodies identify discrete disease subsets in RA, suggesting that heavy chain usage drives distinct effector mechanisms of anti-PAD4 antibodies in RA.

Serum autoantibodyome reveals that healthy individuals share common autoantibodies

SUMMARYAutoantibodies are a hallmark of both autoimmune disease and cancer, but they also occur in healthy individuals. Here, we perform a meta-analysis of nine datasets and focus on the common autoantibodies shared by healthy individuals. We report 77 common autoantibodies based on the protein microarray data obtained from probing 182 healthy individual sera on 7,653 human proteins and an additional 90 healthy individual sera on 1,666 human proteins. There is no gender bias; however, the number of autoantibodies increase with age, plateauing around adolescence. We use a bioinformatics pipeline to determine possible molecular-mimicry peptides that can contribute to the elicitation of these common autoantibodies. There is enrichment of intrinsic properties of proteins like hydrophilicity, basicity, aromaticity, and flexibility for common autoantigens. Subcellular localization and tissue-expression analysis reveal that several common autoantigens are sequestered from the circulating autoantibodies.

Temporal Dynamics of Anti-Type 1 Interferon Autoantibodies in Patients With Coronavirus Disease 2019.

Binding levels and neutralization activity of anti–type 1 interferon autoantibodies peaked during acute coronavirus disease 2019 and markedly decreased thereafter. Most patients maintained some ability to neutralize type 1 interferon into convalescence despite lower levels of binding immunoglobulin G. Identifying these autoantibodies in healthy individuals before the development of critical viral disease may be challenging.

A 1,035-Subject Study Suggesting a History of Bone Fracture as a Possible Factor Associated with the Development of Anti-BP180 Autoantibodies

Bullous pemphigoid (BP) is an autoimmune blistering disorder that presents as tense blister formation on the body (Schmidt and Zillikens, 2013). BP autoantibodies target two hemidesmosomal components in basal keratinocytes: BP180 and BP230 (Schmidt and Zillikens, 2013). In BP, 80‒90% of autoantibodies target the NC16A domain of BP180 (Ishiko et al., 1993). It remains largely unclear why anti-BP180 autoantibodies develop in certain individuals, and there is limited information about the prevalence of anti-BP180 autoantibodies in healthy individuals.

Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.

Association of Environmental Exposures and Socioeconomic Status with Presymptomatic Type 1 Diabetes Incidence in Children in Bavaria, Germany

BACKGROUND AND AIM: Increasing incidence of early-onset type 1 diabetes (T1D) has been reported worldwide. Evidence shows that environmental exposures contribute to developing pancreatic islet autoantibodies in individuals with predisposing genes. This study aimed to investigate the effect of environmental exposures and socioeconomic levels on childhood presymptomatic T1D incidence (defined as having at least 2 islet autoantibodies) in Bavaria, Germany. METHODS: Long-term exposure to air pollution (nitrogen dioxide (NO2), Ozone (O3) and particulate matter with a diameter 2.5 μm (PM2.5)) and ambient temperature as well as surrounding greenness and area-level socioeconomic status (SES) were assigned to the residential addresses of 52,636 children (6 years of age) participating in the Fr1da study from 2015 to 2019. Information on demographic characteristics was extracted from self-administered questionnaires. We applied generalized additive models to examine the association of environmental factors and SES with presymptomatic T1D incidence adjusting for sex, age and family history of diabetes. We inspected single as well as multi-exposure models. RESULTS:225 children were diagnosed with presymptomatic T1D. Higher age at the time of diagnosis and having family history of diabetes was related to developing presymptomatic T1D (p0.00). An interquartile range (IQR) increase in O3 was associated with significantly higher odds of developing presymptomatic T1D (IQR: 5.06, Odds ratio (OR): 1.26; 95% confidence interval (CI): 1.08-1.48). One IQR increase in ambient temperature had an inverse association (IQR: 0.92, OR: 0.78, 95% CI: 0.66-0.93). Multi-exposure models indicated similar results, though both effects estimates were slightly shifted to the null. Other exposures were not associated with presymptomatic T1D. CONCLUSIONS:Exposure to higher levels of O3 and low ambient temperature may predispose to T1D development in children. KEYWORDS: Air pollution, Long-term exposure, Ozone, Temperature, Green space, Socio-economic factors

IgM and IgA augmented autoantibody signatures improve early-stage detection of colorectal cancer prior to nodal and distant spread.

ObjectivesTumor‐associated autoantibodies (AAbs) in individuals with cancer can precede clinical diagnosis by several months to years. The objective of this study was to determine whether the primary immune response in form of IgM and gut mucosa‐associated IgA can aid IgG AAbs in the detection of early‐stage colorectal cancer (CRC).MethodsWe developed a novel protein array comprising 492 antigens seropositive in CRC. The array was used to profile IgG, IgM and IgA antibody signatures in 99 CRC patients and 99 sex‐ and age‐matched non‐cancer controls. A receiver operating curve (ROC), Kaplan–Meier survival analysis and univariate and multivariate Cox regression analyses were conducted.ResultsWe identified a panel of 16 multi‐isotype AAbs with a cumulative sensitivity of 91% and specificity of 74% (AUC 0.90, 95% CI: 0.850–0.940) across all CRC stages. IgM and IgG isotypes were conversely associated with disease stage with IgM contributing significantly to improved stage I and II sensitivity of 96% at 78% specificity (AUC 0.928, 95% CI: 0.884–0.973). A single identified IgA AAb reached an overall sensitivity of 5% at 99% specificity (AUC 0.520, 95% CI: 0.440–0.601) balanced across all CRC stages. Kaplan–Meier analysis revealed that se33‐1 (ZNF638) IgG AAbs were associated with reduced 5‐year overall survival (log‐rank test, P = 0.012), whereas cumulative IgM isotype signatures were associated with improved 5‐year overall survival (log‐rank test, P = 0.024).ConclusionIgM AAbs are associated with early‐stage colorectal cancer. Combining IgG, IgM and IgA AAbs is a novel strategy to improve early diagnosis of cancers.

Cardiospecific autoantibodies in people with vibration disease and type 2 diabetes mellitus

Background . Metabolic syndrome and diabetes mellitus (DM), as well as a number of environmental factors increase the risk of cardiovascular diseases, which are the leading causes of mortality among working population. Objective . To assess the levels of specific autoantibodies in individuals with vibration disease and type 2 DM. Design and methods . People with vibration disease (group I), patients with type 2 DM (group II), and patients with vibration disease and type 2 DM (group III) were examined. The serum level content of autoantibodies related to vascular state was studied using enzyme immunoassay. Results . More than a quarter of all examined patients had elevated levels of antibodies to the РАРР-А. The changes in the serum level of cardiospecific autoantibodies indicate endothelial damage, alterations of thrombus formation and vascular inflammation. People with vibration disease showed increased incidence of hypoimmunoreactivity of antibodies to collagen, nitric oxide synthase, platelet membrane components, neutrophil and endotheliocyte cytoplasm. Patients with DM had the highest levels of autoantibodies to collagen, nitric oxide synthase, and platelet membrane components. In these patients, increased level of specific autoantibodies to nitric oxide synthase and collagen were found more common. Patients with comorbid pathology showed similar changes: higher rate of reduced level of antibodies to platelet membrane components, nitric oxide synthase and increased level of autoantibodies to nitric oxide synthase and collagen.

Comparative assessment of cardiac-specific autoantibodies levels in persons with occupational pathology caused by exposure to physical and chemical factors

Introduction. The pathology of the cardiovascular system is one of the dominant causes of mortality. It has been established that exposure to vibration and mercury is associated with the development of heart and vascular diseases. Specific autoantibodies can be used as markers of exposure effects. The aim of the work was a comparative assessment of the levels of cardiac-specific autoantibodies in individuals with vibrational disease (VD) and chronic mercury intoxication. Material and methods. We examined VD patients, with chronic mercury intoxication (CMI), who work in contact with a toxicant and in the long-term post-exposure period, and the comparison group. The relative content of specific autoantibodies to nitric oxide synthase (NOS), platelet membrane components (PMC), neutrophil cytoplasm, and vascular endothelial cell antigens (c-ANCA), plasminogen, collagen, and PAPP-A protein were studied in the patient’s blood serum. Results. In individuals with CMI, the levels of autoantibodies PCM, c-ANCA are lower for plasminogen and higher for collagen than in the comparison group and in VD patients. Elevated levels of anti-collagen antibodies were found in 70% of individuals with CMI. Among patients with CMI, elevated levels of antibodies to NOS were found in 60% of persons exposed to mercury and were not detected in the long-term post-exposure period. Discussion. The high frequency of elevated levels of antibodies to collagen and correlations between their level and the rest of the indices may indicate its important role in the development of endothelial dysfunction in persons with CMI. Elevated levels of autoantibodies to NOS in patients exposed to mercury are accompanied by a decrease in NO levels and may be an important part of the pathogenesis of endothelial dysfunction. Conclusion. The profile of cardiac-specific autoantibodies in VD patients is similar to that in the comparison group. Elevated levels of antibodies to collagen and decreased levels of antigens of platelets and plasminogen play an important role in the development of endothelial dysfunction in patients with CMI. The high frequency of hyper immunoreactivity of autoantibodies to NOS and c-ANCA, which is observed in patients with CMI who are in contact with a toxicant, decreases in the long-term post-exposure period.

Arthritis autoantibodies in individuals without rheumatoid arthritis: follow-up data from a Dutch population-based cohort (Lifelines).

ObjectivesTo assess whether the presence of arthritis autoantibodies alongside IgG ACPA predicts clinically suspect arthralgia in ACPA-positive subjects without RA.MethodsIn the population-based Lifelines cohort (n = 40 136), 308 IgG ACPA-positive individuals without RA were present. Serum levels of IgA ACPA, IgA and IgM RF, and IgG anti-carbamylated antibodies were measured at baseline. Individuals were divided based on the Connective tissue disease Screening Questionnaire after 2 years follow-up. Antibodies to Porphyromonas gingivalis were determined at baseline and related to presence of periodontitis and joint complaints at 2 years follow-up.ResultsOf 308 subjects 53.6% were also seropositive for IgA ACPA, 42.2% for IgM RF, 23.7% for IgA RF and 13.6% for anti-carbamylated antibodies. We defined 75 persons with clinically suspect arthralgia at risk for RA based on CTD Screening Questionnaire at follow-up. Significantly more seropositivity for IgM RF and higher levels of IgG ACPA, IgA ACPA and IgM RF were found in clinically suspect arthralgia compared with no-clinically suspect arthralgia. In multivariate logistic regression correcting for age, gender and never smoking, positivity for three or more extra autoantibodies was significantly associated with clinically suspect arthralgia. Although levels of anti-P. gingivalis were not different between groups, they were significantly correlated to levels of both RFs, and both ACPAs in clinically suspect arthralgia.ConclusionsACPA-positive individuals without RA who develop clinically suspect arthralgia have more and higher levels of other arthritis autoantibodies at baseline. Levels of anti-P. gingivalis are not related to self-reported periodontitis or clinically suspect arthralgia, but are correlated to arthritis autoantibodies in clinically suspect arthralgia.

Cytokine Autoantibodies Are Associated with Infection Risk and Self-Perceived Health: Results from the Danish Blood Donor Study

The presence of naturally occurring cytokine-specific autoantibodies (c-aAb) in humans is well established, as well as associations to selected pathologies. However, the overall influence of c-aAb on immunocompetence remains largely unknown. In this paper, we performed a large-scale investigation of c-aAb association with infection risk. A cohort of healthy Danish blood donors was screened for c-aAb against IL-1α, IL-6, IL-10, IFNα, and GM-CSF using a Luminex-based multiplex assay, and results were linked to data from the Danish National Prescription Registry. The filing of an antimicrobial prescription following c-aAb measurement was used as a proxy for impaired immunocompetence. We found that c-aAb against pro-inflammatory cytokines IFNα and GM-CSF tended to associate with increased risk of prescription filings in women, whereas antibodies against anti-inflammatory IL-10 were associated with a lower predicted risk of antimicrobial prescriptions, as well as higher self-perceived health scores. We also observed an association of cumulative c-aAb presence with prescription risk. Our data show that cytokine autoantibodies in healthy individuals associate with various proxies for immunomodulation, with the exact association dependent on the pattern of pro- or anti-inflammatory cytokines targeted. This suggests that c-aAb may express cytokine-modulatory properties in healthy individuals and may be critical to further investigate as biomarkers of immunodeficiency.

Autoimmunity and glaucoma

AbstractSeveral clinical studies were able to demonstrate alterations in the abundances of various autoantibodies in individuals with glaucoma. Interestingly, these changes in serum antibody profiles of glaucoma patients are stable among different study populations and differ between the different glaucoma subtypes. Thereby, not only antibodies with a higher concentration but also such with a lower level in glaucoma patients in comparison to healthy individuals have been observed. Of particular interest here are the low abundant antibodies present in glaucoma patients since they display neuroprotective properties in vitro and in glaucoma animal model, and could hold a hitherto unused therapeutic potential. Although glaucoma is not considered a classical autoimmune disease, these changes in antibody profiles hold an enormous diagnostic potential based on autoimmune biomarkers and could additionally open up new therapeutic options.