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Frontiers in Immunology 2023Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low...
Comprehensive autoantibody evaluation is essential for the management of autoimmune disorders. However, conventional methods suffer from poor sensitivity, low throughput, or limited availability. Here, using a proteome-wide human cDNA library, we developed a novel multiplex protein assay (autoantibody array assay; A-Cube) covering 65 antigens of 43 autoantibodies that are associated with systemic sclerosis (SSc) and polymyositis/dermatomyositis (PM/DM). The performance of A-Cube was validated against immunoprecipitation and established enzyme-linked immunosorbent assay. Further, through an evaluation of serum samples from 357 SSc and 172 PM/DM patients, A-Cube meticulously illustrated a diverse autoantibody landscape in these diseases. The wide coverage and high sensitivity of A-Cube also allowed the overlap and correlation analysis between multiple autoantibodies. Lastly, reviewing the cases with distinct autoantibody profiles by A-Cube underscored the importance of thorough autoantibody detection. Together, these data highlighted the utility of A-Cube as well as the clinical relevance of autoantibody profiles in SSc and PM/DM.
Topics: Humans; Autoantibodies; Autoimmunity; Protein Array Analysis; Autoimmune Diseases; Scleroderma, Systemic; Dermatomyositis
PubMed: 37701440
DOI: 10.3389/fimmu.2023.1255540 -
Zeitschrift Fur Rheumatologie Apr 2024Idiopathic inflammatory myopathy (IIM) is a group of rare and heterogeneous systemic diseases that manifest not only in the muscles but also in the skin, joints, and... (Review)
Review
Idiopathic inflammatory myopathy (IIM) is a group of rare and heterogeneous systemic diseases that manifest not only in the muscles but also in the skin, joints, and lungs. Initial symptoms can be isolated and variable and thus the diagnosis poses challenges to various specialist groups. As autoantibodies are sometimes the only specific findings that lead to the diagnosis and appropriate treatment, basic knowledge of them is essential. This article explains the available test systems, names the clinical indications necessary for the initiation of autoantibody diagnostics, provides information on the etymology, antigens, synonyms, and first descriptors, describes indirect immunofluorescence on HEp‑2 cells induced by myositis antibodies, and provides clinical-serological associations. The comparison of the autoantibody findings with the clinical symptoms and laboratory findings enables the identification of false positive or false negative laboratory findings in the sense of a plausibility check.
Topics: Humans; Autoantibodies; Myositis
PubMed: 38294510
DOI: 10.1007/s00393-024-01476-0 -
Molecular Immunology Nov 2022The complement system is recognized as a major pathogenic or contributing factor in an ever-growing number of diseases. In addition to inherited factors, autoantibodies... (Review)
Review
The complement system is recognized as a major pathogenic or contributing factor in an ever-growing number of diseases. In addition to inherited factors, autoantibodies to complement proteins have been detected in various systemic and organ-specific disorders. These include antibodies directed against complement components, regulators and receptors, but also protein complexes such as autoantibodies against complement convertases. In some cases, the autoantibodies are relatively well characterized and a pathogenic role is incurred and their detection has diagnostic value. In other cases, the relevance of the autoantibodies is rather unclear. This review summarizes what we know of complement specific autoantibodies in diseases and identifies unresolved questions regarding their functional effect and relevance.
Topics: Autoantibodies; Complement Activation; Complement System Proteins
PubMed: 36084516
DOI: 10.1016/j.molimm.2022.08.011 -
Allergology International : Official... Apr 2017Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of...
BACKGROUND
Autoimmune involvement in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD) has been proposed, and autoantibodies are a hallmark of autoimmunity. This study aimed to compare the autoantibody profiles of asthma and COPD, and the relationship between autoantibodies and features of these diseases.
METHODS
We recruited 110 asthma patients and 92 COPD patients for a prospective study. Six autoantibody types were evaluated: antinuclear antibody, anti-cytoplasmic antibodies, rheumatoid factor, anti-cyclic citrullinated peptide antibody, myeloperoxidase-anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and proteinase 3-ANCA. Other clinical data were also recorded concurrently.
RESULTS
An antinuclear antibody titre of ≥1:160 presented only in asthma but not in COPD (10% vs. 0%, p = 0.0002). Eosinophil counts in blood were negative predictors of antinuclear antibody in asthma. Conversely, eosinophil counts in blood and immunoglobulin-E levels of ≥100 IU/mL were positively associated with rheumatoid factor in asthma but not in COPD. There was no relationship between antinuclear antibody or rheumatoid factor and disease severity.
CONCLUSIONS
It is possible that asthma tends to involve autoimmunity associated with antinuclear antibody more frequently than COPD because asthma is the more robust factor for antinuclear antibody positivity. Antinuclear antibody and rheumatoid factor are associated with eosinophilic responses, but they do not work as biomarkers for disease severity.
Topics: Aged; Aged, 80 and over; Asthma; Autoantibodies; Biomarkers; Eosinophils; Female; Humans; Leukocyte Count; Male; Middle Aged; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Risk Factors
PubMed: 27592398
DOI: 10.1016/j.alit.2016.08.005 -
Current Opinion in Rheumatology Nov 2014The purpose of this review is to highlight recent progress in autoantibody detection technologies and describe how these methods are providing novel information and... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to highlight recent progress in autoantibody detection technologies and describe how these methods are providing novel information and insights into autoimmune disorders.
RECENT FINDINGS
In recent years, alternative methods such as comprehensive phage display, fluid-phase immunoassays, and antigen microarrays have been developed for autoantigen discovery and profiling autoantibody responses. Compared with classic approaches such as Western blot and ELISA, these methods show improved diagnostic performance, the ability to measure antibody responses to multiple targets, and/or allow more quantitative analyses. Specific notable findings include uncovering previously unrecognized autoantigens, the improved classification of patient clinical phenotypes, and the discovery of pathogenic autoantibodies promoting disease.
SUMMARY
Advances in immunoassay technologies offer many opportunities for understanding the relationship between autoantibody detection and the myriad complex, clinical phenotypes characteristic of most autoimmune diseases. Further simplification and standardization of these technologies may allow routine integration into clinical practice with improved diagnostic and therapeutic outcomes.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Humans; Immunoassay
PubMed: 25203116
DOI: 10.1097/BOR.0000000000000107 -
Expert Review of Clinical Immunology 2016In this review we explore the different characteristics of the serological phenotypes identified in juvenile-onset myositis and consider how the serological... (Review)
Review
In this review we explore the different characteristics of the serological phenotypes identified in juvenile-onset myositis and consider how the serological sub-classification of patients with juvenile myositis can be advantageous both in terms of reaching what can be a difficult diagnosis and informing on prognosis. Recent studies have described the autoantibody associated disease phenotypes and outcome for those with juvenile-onset disease and include analyses of large juvenile-onset myositis cohorts. Here we describe the autoantibody associated disease features for patients within juvenile-onset myositis in detail and discuss the expanding opportunities and strategies for myositis specific autoantibody testing in clinical practice.
Topics: Adolescent; Animals; Autoantibodies; Dermatomyositis; Humans; Muscle, Skeletal; Myositis; Prognosis; Serologic Tests
PubMed: 26651264
DOI: 10.1586/1744666X.2016.1131126 -
Frontiers in Immunology 2024Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis... (Review)
Review
Autoimmune blistering disorders (AIBDs) are a heterogeneous group of approximately a dozen entities comprising pemphigus and pemphigoid disorders and dermatitis herpetiformis. The exact diagnosis of AIBDs is critical for both prognosis and treatment and is based on the clinical appearance combined with the detection of tissue-bound and circulating autoantibodies. While blisters and erosions on the skin and/or inspectable mucosal surfaces are typical, lesions may be highly variable with erythematous, urticarial, prurigo-like, or eczematous manifestations. While direct immunofluorescence microscopy (IFM) of a perilesional biopsy is still the diagnostic gold standard, the molecular identification of the major target antigens opened novel therapeutic avenues. At present, most AIBDs can be diagnosed by the detection of autoantigen-specific serum antibodies by enzyme-linked immunosorbent assay (ELISA) or indirect IFM when the clinical picture is known. This is achieved by easily available and highly specific and sensitive assays employing recombinant immunodominant fragments of the major target antigens, i.e., desmoglein 1 (for pemphigus foliaceus), desmoglein 3 (for pemphigus vulgaris), envoplakin (for paraneoplastic pemphigus), BP180/type XVII collagen (for bullous pemphigoid, pemphigoid gestationis, and mucous membrane pemphigoid), laminin 332 (for mucous membrane pemphigoid), laminin β4 (for anti-p200 pemphigoid), type VII collagen (for epidermolysis bullosa acquisita and mucous membrane pemphigoid), and transglutaminase 3 (for dermatitis herpetiformis). Indirect IFM on tissue substrates and in-house ELISA and immunoblot tests are required to detect autoantibodies in some AIBD patients including those with linear IgA disease. Here, a straightforward modern approach to diagnosing AIBDs is presented including diagnostic criteria according to national and international guidelines supplemented by long-term in-house expertise.
Topics: Humans; Autoantibodies; Autoimmune Diseases; Autoantigens; Skin Diseases, Vesiculobullous; Enzyme-Linked Immunosorbent Assay
PubMed: 38903493
DOI: 10.3389/fimmu.2024.1363032 -
Current Opinion in Rheumatology Nov 2019To review the advances that have been made in our understanding of the genetics of idiopathic inflammatory myopathies (IIM) in the past 2 years, with a particular focus... (Meta-Analysis)
Meta-Analysis Review
PURPOSE OF REVIEW
To review the advances that have been made in our understanding of the genetics of idiopathic inflammatory myopathies (IIM) in the past 2 years, with a particular focus on dermatomyositis and polymyositis.
RECENT FINDINGS
Fine-mapping studies in the major histocompatibility complex region in Caucasian and Korean populations have identified novel human leukocyte antigen (HLA) variants that are associated with autoantibody subgroups in IIM. Differences in HLA associations have been identified between Caucasian adult-onset and juvenile-onset patients with anti-TIF1 autoantibodies, suggesting distinct aetiologies in these patients. For some autoantibodies, the strongest associations identified are specific amino acid positions within HLA molecules, providing mechanistic insights into disease pathogenesis.A meta-analysis combining data from four seropositive rheumatic diseases identified 22 novel non-HLA associations in IIM, of which seven were previously reported at suggestive significance in IIM. A genome-wide association study conducted in the Japanese population identified a significant association with WDFY4 in patients with clinically amyopathic dermatomyositis.
SUMMARY
Considerable progress has been made in understanding the genetics of IIM, including differences in clinical and autoantibody subgroups. As research continues, there should be a focus to increase statistical strength and precision by conducting meta-analyses and trans-ethnic studies.
Topics: Autoantibodies; Autoimmunity; Genome-Wide Association Study; HLA Antigens; Humans; Myositis
PubMed: 31415030
DOI: 10.1097/BOR.0000000000000652 -
Immunopharmacology and Immunotoxicology 2016Although autoantibody detection methods such as indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) have been available for many years and... (Review)
Review
CONTEXT
Although autoantibody detection methods such as indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) have been available for many years and are still in use the innovation of fast, fully automated instruments using chemiluminescence technology in recent years has led to rapid adoption in autoimmune disease diagnostics. In 2009, BIO-FLASH, a fully automated, random access chemiluminescent analyzer, was introduced, proceeded by the development of the QUANTA Flash chemiluminescent immunoassays (CIA) for autoimmune diagnostics.
OBJECTIVE
To summarize the evolution of CIAs for the detection of autoantibodies and to review their performance characteristics.
METHODS
Pubmed was screened for publications evaluating novel QUANTA Flash assays and how they compare to traditional methods for the detection of autoantibodies. In addition, comparative studies presented at scientific meetings were summarized.
RESULTS
Several studies were identified that compared the novel CIAs with conventional methods for autoantibody detection. The agreements ranged from moderate to excellent depending on the assay. The studies show how the CIA technology has enhanced the analytical and clinical performance characteristics of many autoantibody assays supporting both diagnosis and follow-up testing.
CONCLUSION
CIA has started to improve the diagnostic testing of autoantibodies as an aid in the diagnosis of a broad range of autoimmune diseases.
Topics: Animals; Autoantibodies; Humans; Luminescent Measurements
PubMed: 26525648
DOI: 10.3109/08923973.2015.1077461 -
Clinical & Developmental Immunology 2012Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus... (Review)
Review
Anti-Ro/SSA antibodies are among the most frequently detected autoantibodies against extractable nuclear antigens and have been associated with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). Although the presence of these autoantibodies is one of the criteria for the diagnosis and classification of SS, they are also sometimes seen in other systemic autoimmune diseases. In the last few decades, the knowledge of the prevalence of anti-Ro/SSA antibodies in various autoimmune diseases and symptoms has been expanded, and the clinical importance of these antibodies is increasing. Nonetheless, the pathological role of the antibodies is still poorly understood. In this paper, we summarize the milestones of the anti-Ro/SSA autoantibody system and provide new insights into the association between the autoantibodies and the pathogenesis of autoimmune diseases.
Topics: Animals; Autoantibodies; Autoimmune Diseases; Humans; Ribonucleoproteins
PubMed: 23304190
DOI: 10.1155/2012/606195