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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 -
Journal of Autoimmunity Feb 2023Myasthenia gravis (MG) is a debilitating autoimmune disease characterized by muscle fatigue and weakness caused by autoantibody- and complement-mediated damage to the...
Myasthenia gravis (MG) is a debilitating autoimmune disease characterized by muscle fatigue and weakness caused by autoantibody- and complement-mediated damage to the neuromuscular junction. This study sought to compare the efficacy of unique sets of monoclonal antibody-siRNA conjugates, individually (mono) or in combination (duo), against the crucial receptors predominantly or solely expressed on two subsets of B cells-plasma B cells and their precursor (transitional mature B) cells in a mouse model of MG. At the optimized doses, the conjugates, likely due to the combined activities of mAb and siRNA, substantially decreased the expression levels of CD268 (B cell-activating factor receptor) in mature B cells and CD269 (B-cell maturation antigen) in plasma cells concomitantly with reducing the levels of acetylcholine receptor (AChR)-specific autoantibodies. PEGylation, but not pretreatment with an antibody against type 1 interferon receptor, further improved duoconjugate-induced reduction in the autoantibody levels. Our results show that the duoconjugate treatment significantly improved the clinical symptoms of MG, consistent with the preservation of bungarotoxin-bound functional AChRs. In the future, developing similar target-specific combination molecules can potentially turn into a new and effective therapeutic approach for MG.
Topics: Mice; Animals; Myasthenia Gravis, Autoimmune, Experimental; RNA, Small Interfering; Receptors, Cholinergic; Antibodies, Monoclonal; Autoantibodies
PubMed: 36640636
DOI: 10.1016/j.jaut.2022.102983 -
Current Opinion in Rheumatology Nov 2023This manuscript reviews recently published advances in the identification of autoimmune inflammatory myopathies (AIM)-specific and AIM-related autoantibodies considered...
PURPOSE OF REVIEW
This manuscript reviews recently published advances in the identification of autoimmune inflammatory myopathies (AIM)-specific and AIM-related autoantibodies considered of value in the workup of patients suspected of having AIM. Newer autoantibodies, developments, and advances in the methodology of testing, the gaps and pitfalls in using these assays as diagnostic biomarkers, and the importance of considering overlap diseases and unique clinical AIM phenotypes are discussed.
RECENT FINDINGS
a).. studies of the various diagnostic platforms (e.g., line immunoassays [LIA]) have clarified their limitations and raise cautions in the interpretation of the results. b).. particle based solid phase multianalyte technology (PMAT) is a promising newer diagnostic platform. c).. elucidation of older and descriptions of newer AIM autoantibody markers provide increasing clinical value by revealing novel clinical features (including AIM subsets and overlap syndromes [OS]) and co-existing malignancies.
SUMMARY
The spectrum of autoantibodies and related biomarkers in AIM continues to expand. Many of these have clear clinical implications in regard to subsets and overlap conditions of AIM, associated malignancy and pathological findings.
Topics: Humans; Autoantibodies; Myositis; Autoimmune Diseases; Biomarkers
PubMed: 37503636
DOI: 10.1097/BOR.0000000000000957 -
Frontiers in Immunology 2019Autoimmune bullous dermatoses (AIBD) encompass a variety of organ-specific autoimmune diseases that manifest with cutaneous and/or mucosal blisters and erosions. They... (Review)
Review
Autoimmune bullous dermatoses (AIBD) encompass a variety of organ-specific autoimmune diseases that manifest with cutaneous and/or mucosal blisters and erosions. They are characterized by autoantibodies targeting structural proteins of the skin, which are responsible for the intercellular contact between epidermal keratinocytes and for adhesion of the basal keratinocytes to the dermis. The autoantibodies disrupt the adhesive functions, leading to splitting and blister formation. In pemphigus diseases, blisters form intraepidermally, whereas in all other disease types they occur subepidermally. Early identification of autoimmune bullous dermatoses is crucial for both treatment and prognosis, particularly as regards tumor-associated disease entities. The diagnosis is based on clinical symptoms, histopathology, direct immunofluorescence to detect antibody/complement deposits, and the determination of circulating autoantibodies. The identification of various target antigens has paved the way for the recent development of numerous specific autoantibody tests. In particular, optimized designer antigens and multiplex test formats for indirect immunofluorescence and ELISA have enhanced and refined the laboratory analysis, enabling highly efficient serodiagnosis and follow-up. This review elaborates on the current standards in the serological diagnostics for autoimmune bullous dermatoses.
Topics: Autoantibodies; Autoimmune Diseases; Humans; Serologic Tests; Skin Diseases, Vesiculobullous
PubMed: 31552014
DOI: 10.3389/fimmu.2019.01974 -
Annals of the Rheumatic Diseases Oct 2023The rheumatic diseases are a diverse group of conditions that can display autoantibody production, functional immune disturbances and systemic disease manifestations.... (Review)
Review
The rheumatic diseases are a diverse group of conditions that can display autoantibody production, functional immune disturbances and systemic disease manifestations. These autoantibodies can serve as markers for classification, diagnosis, prognosis and disease activity. Among specificities prominently expressed by patients, those directed to nuclear antigens (antinuclear antibodies or ANAs) are markers for specific rheumatic diseases. ANAs can bind to DNA, RNA and complexes of proteins with nucleic acids. Other autoantibodies expressed in the rheumatic diseases are directed to proteins, including IgG, post-translational modifications of proteins and soluble mediators such as cytokines. While autoantibodies have been investigated for over 50 years, recent studies published in the ) have provided an exciting perspective on the mechanisms of autoantibody production and the power of new technologies to identify novel autoantibody targets to elucidate aetiology and underpin patient evaluation. Furthermore, in-depth serological studies have demonstrated a phenomenon known as clustering; clustering defines sets of autoantibodies that are commonly expressed together in patients with a given rheumatic disease. Other research reported in has used B cell phenotyping and genotypic analysis to subtype patients, and has explored the relationship of autoantibodies, complement activation and patterns of gene expression as exemplified by the interferon gene signature. Together, these studies provide important new insights into disease mechanisms as well as actionable information to facilitate personalised patient care.
Topics: Humans; Autoantibodies; Antibodies, Antinuclear; Rheumatic Diseases; Biomarkers; Prognosis
PubMed: 37580110
DOI: 10.1136/ard-2023-224692 -
Seminars in Immunopathology Jul 2022B cells are central for the adaptive immune system to mount successful immune responses not only as antibody producers but also as regulators of cellular immunity. These... (Review)
Review
B cells are central for the adaptive immune system to mount successful immune responses not only as antibody producers but also as regulators of cellular immunity. These multifaceted features are also reflected in autoimmunity where autoreactive B cells can fuel disease by production of cytotoxic autoantibodies, presentation of autoantigens to autoreactive T cells, and secretion of cytokines and chemokines that either promote detrimental immune activation or impair regulatory T and B cells. The role of B cells and autoantibodies in autoimmune hepatitis (AIH) have been controversially discussed, with typical autoantibodies and hypergammaglobulinemia indicating a key role, while strong HLA class II association suggests T cells as key players. In this review, we summarize current knowledge on B cells in AIH and how different B cell subpopulations may drive AIH progression beyond autoantibodies. We also discuss recent findings of B cell-directed therapies in AIH.
Topics: Autoantibodies; Autoantigens; Autoimmunity; B-Lymphocytes; Hepatitis, Autoimmune; Humans
PubMed: 35488094
DOI: 10.1007/s00281-022-00937-5 -
Lupus Science & Medicine Apr 2023To explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).
OBJECTIVE
To explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).
METHODS
Eighty-seven patients with JSLE were retrospectively collected and divided into subgroups via a two-step cluster based on the status of nine autoantibodies (double-stranded-DNA (dsDNA), nucleosome, histone, ribosomal P protein, Smith (Sm), u1-ribonucleoprotein (RNP), Sjögren's syndrome antigen A (SSA)/Ro52, SSA/Ro60, Sjögren's syndrome antigen B (SSB)/La). The final model selected in this study was based on adequate goodness of fit of the Silhouette coefficient and clinical interpretability. Clinical manifestations, organ involvements and disease activity were compared among the subgroups. Fluctuation in autoantibody status was also collected and analysed. Flare-free survival rates of the patients with positive/negative seroconversion and patients without seroconversion were studied by the Kaplan-Meier method and compared using a log-rank test.
RESULTS
Two clusters were identified: subgroup 1 (positive anti-Sm/RNP group) and subgroup 2 (negative anti-Sm/RNP group). There were more lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) cases in subgroup 1 than in subgroup 2. Patients in subgroup 1 exhibited higher SLE Disease Activity Index scores compared with those in subgroup 2. Furthermore, anti-ribosomal P protein (61.1%), anti-nucleosome (58.3%) and anti-dsDNA (54%) were most commonly positive autoantibodies. A progressive decrease in the frequency of patients with positive results was demonstrated during the follow-up years. The decrease was notable for anti-dsDNA, anti-nucleosome and anti-ribosomal P protein (remaining 27.27%, 38.89% and 45.00% positive in the fifth year, respectively). While for those negative at baseline diagnosis, the decrease in the frequency of negative results was progressive but modest. Kaplan-Meier curve showed that the flare-free survival of patients with positive seroconversion was significantly lower than those without seroconversion and those with negative seroconversion (p<0.001).
CONCLUSIONS
In children with SLE, subgroups based on autoantibody profile can be applied to differentiate phenotypes and disease activity. Two important organ involvements, LN and NPSLE, are more common in patients with positive anti-Sm/RNP autoantibodies. Positive seroconversion may provide a valuable perspective for assessing flare, and it is worthwhile to retest the array of autoantibodies during follow-up.
Topics: Humans; Autoantibodies; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Retrospective Studies; Seroconversion; Antibodies, Antinuclear; Lupus Nephritis; DNA
PubMed: 37012058
DOI: 10.1136/lupus-2022-000834