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Diabetes Care Apr 2020Most individuals with two or more islet autoantibodies progress to clinical type 1 diabetes. However, in some individuals, autoantibodies are subsequently lost. Here,...
OBJECTIVE
Most individuals with two or more islet autoantibodies progress to clinical type 1 diabetes. However, in some individuals, autoantibodies are subsequently lost. Here, our objectives were to determine the frequency of autoantibody loss (reversion) in multiple-autoantibody-positive individuals and to determine the association between reversion and progression to clinical disease.
RESEARCH DESIGN AND METHODS
We analyzed multiple-autoantibody-positive individuals participating in TrialNet's Pathway to Prevention Study for reversion and determined the effect of reversion on progression to clinical disease using a Cox regression analysis.
RESULTS
Of 3,284 multiple-autoantibody-positive subjects, reversion occurred in 134 (4.1%) and was associated with reduced incidence of clinical disease. Reversion occurred more frequently with older age, lower autoantibody titers, and fewer positive autoantibodies.
CONCLUSIONS
Although reversion of multiple-autoantibody positivity is rare, when it occurs, the risk of progressing to clinical disease is reduced. This suggests unknown mechanisms promoting immune remission in some individuals.
Topics: Adolescent; Adult; Autoantibodies; Child; Child, Preschool; Diabetes Mellitus, Type 1; Disease Progression; Female; Humans; Incidence; Infant; Infant, Newborn; Islets of Langerhans; Male; Middle Aged; Remission, Spontaneous; Young Adult
PubMed: 32019856
DOI: 10.2337/dc19-1731 -
Arthritis Research & Therapy Jul 2023Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether...
BACKGROUND
Anti-Jo-1 autoantibodies represent essential markers in the diagnosis of antisynthetase syndrome (ASS). In this retrospective study, we aimed to investigate whether their concentrations and fluctuations could both respectively reflect the severity and evolution of ASS.
METHODS
Between 2015 and 2020, clinical and biological features of ASS patients with at least one positive measure of anti-Jo-1 autoantibody were collected. At each serum sampling, we assessed myositis activity by using the Myositis Intention to Treat Activities Index (MITAX) and compared anti-Jo-1 concentrations with ASS severity, anti-Jo-1 concentrations between patients with and without active disease, and changes in anti-Jo-1 concentrations with disease activity.
RESULTS
Forty-eight patients with ASS had at least one positive determination of anti-Jo-1 concentration. Among them, twenty-nine patients had at least two determinations of anti-Jo-1 autoantibody in their follow-up. We showed that these autoantibody concentrations were significantly correlated with MITAX (r = 0.4, p = 0.03) and creatine kinase concentration (r = 0.34, p = 0.002) and that they were significantly higher in patients with active disease than in those with inactive disease (91.7 IU/L vs 44.4 IU/L, p = 0.016). During follow-up, we found a significant correlation between fluctuations of anti-Jo-1 autoantibody concentrations and MITAX score (r = 0.7, p < 0.0001).
CONCLUSION
Our results suggest that anti-Jo-1 autoantibody concentration could be a predictive marker of the severity and evolution of ASS and show that their quantification could represent a precious tool for disease monitoring and for improving the therapeutic management of ASS patients.
Topics: Humans; Autoantibodies; Biomarkers; Myositis; Retrospective Studies
PubMed: 37481643
DOI: 10.1186/s13075-023-03116-5 -
Frontiers in Immunology 2023The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase...
BACKGROUND
The chronic airway inflammation in severe eosinophilic asthma (SEA) suggests potential autoimmune aetiology with unidentified autoantibodies analogous to myeloperoxidase (MPO) in ANCA-positive EGPA (eosinophilic granulomatosis with polyangiitis). Previous research has shown that oxidative post-translational modification (oxPTM) of proteins is an important mechanism by which autoantibody responses may escape immune tolerance. Autoantibodies to oxPTM autoantigens in SEA have not previously been studied.
METHODS
Patients with EGPA and SEA were recruited as well as healthy control participants. Autoantigen agnostic approach: Participant serum was incubated with slides of unstimulated and PMA-stimulated neutrophils and eosinophils, and autoantibodies to granulocytes were identified by immunofluorescence with anti-human IgG FITC antibody. Target autoantigen approach: Candidate proteins were identified from previous literature and FANTOM5 gene set analysis for eosinophil expressed proteins. Serum IgG autoantibodies to these proteins, in native and oxPTM form, were detected by indirect ELISA.
RESULTS
Immunofluorescence studies showed that serum from patients with known ANCA stained for IgG against neutrophils as expected. In addition, serum from 9 of 17 tested SEA patients stained for IgG to PMA-stimulated neutrophils undergoing NETosis. Immunofluorescent staining of eosinophil slides was evident with serum from all participants (healthy and with eosinophilic disease) with diffuse cytoplasmic staining except for one SEA individual in whom subtle nuclear staining was evident. FANTOM5 gene set analysis identified TREM1 (triggering receptor expressed on myeloid cells 1) and IL-1 receptor 2 (IL1R2) as eosinophil-specific targets to test for autoantibody responses in addition to MPO, eosinophil peroxidase (EPX), and Collagen-V identified from previous literature. Indirect ELISAs found high concentrations of serum autoantibodies to Collagen-V, MPO, and TREM1 in a higher proportion of SEA patients than healthy controls. High concentrations of serum autoantibodies to EPX were evident in serum from both healthy and SEA participants. The proportion of patients with positive autoantibody ELISAs was not increased when examining oxPTM compared to native proteins.
DISCUSSION
Although none of the target proteins studied showed high sensitivity for SEA, the high proportion of patients positive for at least one serum autoantibody shows the potential of more research on autoantibody serology to improve diagnostic testing for severe asthma.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier, NCT04671446.
Topics: Humans; Antibodies, Antineutrophil Cytoplasmic; Triggering Receptor Expressed on Myeloid Cells-1; Churg-Strauss Syndrome; Granulomatosis with Polyangiitis; Autoantigens; Autoantibodies; Asthma; Pulmonary Eosinophilia; Immunoglobulin G
PubMed: 37334358
DOI: 10.3389/fimmu.2023.1164941 -
Eye (London, England) Feb 2017Glaucoma, a leading cause of irreversible blindness worldwide, is often not diagnosed until many years after disease onset. Early and objective diagnostic measures are...
Glaucoma, a leading cause of irreversible blindness worldwide, is often not diagnosed until many years after disease onset. Early and objective diagnostic measures are yet missing. Besides the main risk factor, an elevated intraocular pressure (IOP), age, sex, and ethnicity are known to affect disease progression and severity. Furthermore, oxidative stress, elevated glutamate concentrations, and an autoimmune component are considered possible risk factors. We could identify several potential proteomic biomarkers in glaucoma and examine distinct changes in the glaucomatous human retina proteome. Using an experimental autoimmune glaucoma animal (EAG) model we could demonstrate an IOP-independent loss of retinal ganglion cells (RGC), which is accompanied by antibody depositions and increased levels of microglia. In a different animal model we showed that intermittent IOP elevations provoke neurodegeneration in the optic nerve and the retina and elicit changes of IgG autoantibody reactivities. The correlation between neuronal damage and changes in autoantibody reactivity suggests that autoantibody profiling could be a useful biomarker for glaucoma. In vivo studies on neuroretinal cells and porcine retinal explants demonstrated a protective effect of antibodies (eg, anti-GFAP) on RGC, which seems to be the result of reduced stress levels in the retina. We conclude that the absence of some autoantibodies in glaucoma patients reflects a loss of the protective potential of natural autoimmunity and may thus encourage neurodegenerative processes. Concluding, autoantibody profiles resemble useful biomarkers for diagnosis, progression and severity of glaucoma. Future longitudinal studies will help to improve early detection and enable better monitoring of disease progression.
Topics: Animals; Autoantibodies; Autoimmunity; Biomarkers; Disease Models, Animal; Disease Progression; Glaucoma; Humans; Immunoglobulin G; Intraocular Pressure; Microglia; Proteomics; Retina; Retinal Ganglion Cells; Swine
PubMed: 28085137
DOI: 10.1038/eye.2016.300 -
The FEBS Journal Dec 2009Autoantibodies against autologous tumor-associated antigens have been detected in the asymptomatic stage of cancer and can thus serve as biomarkers for early cancer... (Review)
Review
Autoantibodies against autologous tumor-associated antigens have been detected in the asymptomatic stage of cancer and can thus serve as biomarkers for early cancer diagnosis. Moreover, because autoantibodies are found in sera, they can be screened easily using a noninvasive approach. Consequently, many studies have been initiated to identify novel autoantibodies relevant to various cancer types. To facilitate autoantibody discovery, approaches that allow the simultaneous identification of multiple autoantibodies are preferred. Five such techniques--SEREX, phage display, protein microarray, SERPA and MAPPing--are discussed here. In the second part of this review, we discussed autoantibodies found in the five most common cancers (lung, breast, colorectal, stomach and liver). The discovery of panels of tumor-associated antigens and autoantibody signatures with high sensitivity and specificity would aid in the development of diagnostics, prognostics and therapeutics for cancer patients.
Topics: Animals; Autoantibodies; Biomarkers, Tumor; Early Detection of Cancer; Electrophoresis, Gel, Two-Dimensional; Humans; Neoplasms; Protein Array Analysis; Proteomics; Sensitivity and Specificity
PubMed: 19860826
DOI: 10.1111/j.1742-4658.2009.07396.x -
Journal of Clinical Rheumatology :... Jan 2023The subset of ANA-positive patients with systemic sclerosis (SSc) who lack prototypic SSc-specific autoantibodies (centromere, topoisomerase, RNA polymerase III,...
BACKGROUND/OBJECTIVES:
The subset of ANA-positive patients with systemic sclerosis (SSc) who lack prototypic SSc-specific autoantibodies (centromere, topoisomerase, RNA polymerase III, “triple negative SSc”) is poorly characterized. We assessed clinical features and prevalence of additional autoantibodies in these patients.
METHODS:
In this case series patients with ANA+ and triple negative SSc antibodies were identified from two independent SSc cohorts (n=280) and demographic and clinical data were obtained over two years. Sera were screened for ANA and autoantibodies were examined by immunoblots. Significance was assessed through Fisher’s exact test and Student’s T-test.
RESULTS:
Forty ANA+ triple negative SSc patients (14% of the two SSc cohorts) were identified. Mean age was 53 ± 14.5 years, 53% had limited disease, average disease duration was 9 ± 9.7 years, and MRSS was 7.6 ± 6.8. 47.5% of the patients had digital ulcers, 60% had interstitial lung disease and 15% had pulmonary hypertension. The most common immunofluorescence patterns were speckled and mixed speckled/nucleolar. Of 29 autoantibodies tested, the most prevalent were Ro-52 (50%), Th/To (40%), MDA5 (35%), SAE1 (28%). Ro-52 was associated with ILD (RR 2.67, p<0.001) and elevated CK (RR 2.64, p<0.05), and PM-75 was associated with digital ulcers (RR 2.18, p<0.05).
CONCLUSIONS:
ANA+ triple negative SSc patients represent an understudied and heterogeneous population of patients with a high prevalence of Ro-52 antibodies, an enrichment for myositis specific antibodies, and increased risk of interstitial lung disease. These patients are seen relatively frequently and should be regularly assessed for evidence of myopathy and lung involvement.
Topics: Humans; Autoantibodies; Antibodies, Antinuclear; Scleroderma, Systemic
PubMed: 35767831
DOI: 10.1097/RHU.0000000000001881 -
Jornal Brasileiro de Pneumologia :... 2013The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can... (Review)
Review
The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease.
Topics: Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Biopsy; Connective Tissue Diseases; Diagnosis, Differential; Humans; Lung Diseases, Interstitial; Prognosis
PubMed: 24473767
DOI: 10.1590/S1806-37132013000600012 -
Genomics, Proteomics & Bioinformatics Aug 2015Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the... (Review)
Review
Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by the production of autoantibodies to a broad range of self-antigens. Profiling the autoantibody repertoire using array-based technology has emerged as a powerful tool for the identification of biomarkers in SLE and other autoimmune diseases. Proteomic microarray has the capacity to hold large number of self-antigens on a solid surface and serve as a high-throughput screening method for the determination of autoantibody specificities. The autoantigen arrays carrying a wide variety of self-antigens, such as cell nuclear components (nucleic acids and associated proteins), cytoplasmic proteins, phospholipid proteins, cell matrix proteins, mucosal/secreted proteins, glomeruli, and other tissue-specific proteins, have been used for screening of autoantibody specificities associated with different manifestations of SLE. Arrays containing synthetic peptides and molecular modified proteins are also being utilized for identification of autoantibodies targeting to special antigenic epitopes. Different isotypes of autoantibodies, including IgG, IgM, IgA, and IgE, as well as other Ig subtypes, can be detected simultaneously with multi-color labeled secondary antibodies. Serum and plasma are the most common biologic materials for autoantibody detection, but other body fluids such as cerebrospinal fluid, synovial fluid, and saliva can also be a source of autoantibody detection. Proteomic microarray as a multiplexed high-throughput screening platform is playing an increasingly-important role in autoantibody diagnostics. In this article, we highlight the use of autoantigen microarrays for autoantibody exploration in SLE.
Topics: Autoantibodies; Autoantigens; Biomarkers; High-Throughput Screening Assays; Humans; Lupus Erythematosus, Systemic; Protein Array Analysis; Proteomics; Saliva; Synovial Fluid
PubMed: 26415621
DOI: 10.1016/j.gpb.2015.09.001 -
Arthritis Research & Therapy May 2020A myositis-specific autoantibody can now be identified in the majority of patients with myositis. They identify homogeneous patient subgroups and are key tools in...
BACKGROUND
A myositis-specific autoantibody can now be identified in the majority of patients with myositis. They identify homogeneous patient subgroups and are key tools in developing a personalized approach to disease management. There is substantial clinical interest in exploiting myositis autoantibodies as biomarkers, and consequently, a large number of commercial assays have been developed for their detection. These assays are already in widespread clinical use. In order to better understand perceived concerns from the international myositis community in relation to the reliability of these assays and how they are being used, we conducted a survey of international myositis experts, all of whom were members of the International Myositis Assessment and Clinical Studies group.
RESULTS
We collected data on the types of assay used, manufacturers, and the nature of the report provided by different laboratories and received 111 complete responses. Respondents also provided information on how they used the different assays, their confidence in the results, and how this influenced their clinical practice. Enzyme immunoassay/ELISA was the most popular assay method used worldwide followed by line blot. Line blot was the most popular method used in Europe. Despite concerns from over 80% of respondents regarding false-positive and false-negative results with the assay used by their laboratory, over 80% reported that the identification of a myositis autoantibody influenced their diagnostic confidence, the information they provided to a patient, and their recommended treatment.
CONCLUSIONS
In spite of ongoing concerns from the majority of users regarding the reliability of the results, myositis-specific autoantibody testing, using commercial immunoassays, is being used globally to inform clinical decision-making. These findings highlight the need for urgent guidance on the use of myositis autoantibody testing and on the interpretation of results. Knowledge of the reliability of currently available assays is essential given the importance already placed on myositis-specific autoantibodies as clinical decision-making tools.
Topics: Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Europe; Humans; Immunoassay; Myositis; Reproducibility of Results
PubMed: 32414409
DOI: 10.1186/s13075-020-02210-2 -
Clinical Reviews in Allergy & Immunology Aug 2017Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune... (Review)
Review
Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune and systemic autoimmune rheumatic diseases (SARD), especially connective tissue diseases (CTDs). Due to the appearance of autoAb profiles in SARD patients and the complexity of the corresponding serological diagnosis, different diagnostic strategies have been suggested for appropriate autoAb testing. Thus, evolving assay techniques and the continuous discovery of novel autoantigens have greatly influenced the development of these strategies. Antinuclear antibody (ANA) analysis by indirect immunofluorescence (IIF) on tissue and later cellular substrates was one of the first tests introduced into clinical routine and is still an indispensable tool for CTD serology. Thus, screening for ANA by IIF is recommended to be followed by confirmatory testing of positive findings employing different assay techniques. Given the continuous growth in the demand for autoAb testing, IIF has been challenged as the standard method for ANA and other autoAb analyses due to lacking automation, standardization, modern data management, and human bias in IIF pattern interpretation. To address these limitations of autoAb testing, the CytoBead® technique has been introduced recently which enables automated interpretation of cell-based IIF and quantitative autoAb multiplexing by addressable microbead immunoassays in one reaction environment. Thus, autoAb screening and confirmatory testing can be combined for the first time. The present review discusses the history of autoAb assay techniques in this context and gives an overview and outlook of the recent progress in emerging technologies.
Topics: Antibodies, Antinuclear; Autoantibodies; Autoimmune Diseases; Autoimmunity; Biomarkers; Fluorescent Antibody Technique, Indirect; Humans
PubMed: 27368807
DOI: 10.1007/s12016-016-8574-3