-
Journal of Autoimmunity Jun 2020Rheumatoid arthritis (RA) is a systemic auto-immune disease principally effecting synovial joints. RA is characterized by immune cell infiltration in the joint. The... (Review)
Review
Rheumatoid arthritis (RA) is a systemic auto-immune disease principally effecting synovial joints. RA is characterized by immune cell infiltration in the joint. The presence of autoantibodies is a hallmark for the disease, among these are rheumatoid factor and antibodies against post-translational modified proteins like citrullination (ACPA) and carbamylation (anti-CarP antibodies). These autoantibodies may form immune complexes in the joint, leading to the attraction of immune cells. Based on the presence of these autoantibodies, RA patients can be subdivided in autoantibody positive and negative disease. Both subsets can be associated with genetic and environmental risk factors for RA, like the human leukocyte antigen (HLA) allele and smoking. Autoantibodies can already be detected years before disease onset in a subgroup of patients and at symptom onset a broad isotype spectrum is observed. This suggests that various events occur prior to the development of RA in which the first autoantibodies develop in predisposed individuals. Therefore, the presence of these autoantibodies can be useful in predicting future RA patients. Research on the characteristics and effector function of these autoantibodies is ongoing and will give more knowledge in the inflammatory responses underlying RA. This will give insight in the pathogenic role of autoantibodies in RA. Recent data are suggestive of a role for mucosal surfaces in the development of auto-immune responses associated with (the development of) RA. In conclusion, investigating the potential pathogenic effector functions of autoantibody isotypes and their molecular- and physicochemical-compositions might improve understanding of the disease origin and its underlying immunological processes. This may lead to the development of new therapeutic targets and strategies.
Topics: Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Autoimmunity; Disease Susceptibility; Environment; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans
PubMed: 31911013
DOI: 10.1016/j.jaut.2019.102392 -
Nature Reviews. Nephrology Aug 2023Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur... (Review)
Review
Autoimmune diseases are a diverse group of conditions characterized by aberrant B cell and T cell reactivity to normal constituents of the host. These diseases occur widely and affect individuals of all ages, especially women. Among these diseases, the most prominent immunological manifestation is the production of autoantibodies, which provide valuable biomarkers for diagnosis, classification and disease activity. Although T cells have a key role in pathogenesis, they are technically more difficult to assay. In general, autoimmune disease results from an interplay between a genetic predisposition and environmental factors. Genetic predisposition to autoimmunity is complex and can involve multiple genes that regulate the function of immune cell populations. Less frequently, autoimmunity can result from single-gene mutations that affect key regulatory pathways. Infection seems to be a common trigger for autoimmune disease, although the microbiota can also influence pathogenesis. As shown in seminal studies, patients may express autoantibodies many years before the appearance of clinical or laboratory signs of disease - a period called pre-clinical autoimmunity. Monitoring autoantibody expression in at-risk populations may therefore enable early detection and the initiation of therapy to prevent or attenuate tissue damage. Autoimmunity may not be static, however, and remission can be achieved by some patients treated with current agents.
Topics: Humans; Female; Genetic Predisposition to Disease; Autoimmune Diseases; Autoimmunity; Autoantibodies; T-Lymphocytes
PubMed: 37165096
DOI: 10.1038/s41581-023-00720-1 -
Journal of Medical Virology Jan 2022Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease... (Review)
Review
Coronavirus disease 2019 (COVID-19) is still propagating a year after the start of the pandemic. Besides the complications patients face during the COVID-19 disease period, there is an accumulating body of evidence concerning the late-onset complications of COVID-19, of which autoimmune manifestations have attracted remarkable attention from the first months of the pandemic. Autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, and the detection of autoantibodies are the cues to the discovery of the potential of COVID-19 in inducing autoimmunity. Clarification of the pathophysiology of COVID-19 injuries to the host, whether it is direct viral injury or autoimmunity, could help to develop appropriate treatment.
Topics: Autoantibodies; Autoimmune Diseases; Autoimmunity; COVID-19; Humans; SARS-CoV-2
PubMed: 34427929
DOI: 10.1002/jmv.27292 -
Frontiers in Immunology 2023Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is... (Review)
Review
Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial contributions of different proinflammatory or inflammatory mediators in the pathogenesis of MG. Despite these findings, compared to therapeutic approaches that target autoantibody and complements, only a few therapeutics against key inflammatory molecules have been designed or tested in MG clinical trials. Recent research focuses largely on identifying unknown molecular pathways and novel targets involved in inflammation associated with MG. A well-designed combination or adjunct treatment utilizing one or more selective and validated promising biomarkers of inflammation as a component of targeted therapy may yield better treatment outcomes. This review briefly discusses some preclinical and clinical findings of inflammation associated with MG and current therapy approaches and suggest the potential of targeting important inflammatory marker(s) along with current monoclonal antibody or antibody fragment based targeted therapies directed to a variety of cell surface receptors.
Topics: Humans; Myasthenia Gravis; Receptors, Cholinergic; Autoantibodies; Muscles; Inflammation
PubMed: 36793733
DOI: 10.3389/fimmu.2023.1110499 -
International Journal of Molecular... Jun 2023Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in... (Review)
Review
Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. A combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate a more accurate diagnosis and prediction of autoimmune disorders. The aim of this review is to summarize what is known about the clinical significance of anti-islet autoantibodies in the pathogenesis and diagnosis of T1D.
Topics: Adult; Humans; Diabetes Mellitus, Type 1; Autoantibodies; Autoimmune Diseases; Insulin; Insulin, Regular, Human; Glutamate Decarboxylase
PubMed: 37373160
DOI: 10.3390/ijms241210012 -
Current Opinion in Rheumatology Mar 2023Autoantibodies are cornerstone biomarkers in systemic lupus erythematosus (SLE), an autoimmune disease characterized by autoantibody-mediated tissue damage.... (Review)
Review
PURPOSE OF REVIEW
Autoantibodies are cornerstone biomarkers in systemic lupus erythematosus (SLE), an autoimmune disease characterized by autoantibody-mediated tissue damage. Autoantibodies can inform about disease susceptibility, clinical course, outcomes and the cause of SLE. Identifying pathogenic autoantibodies in SLE, however, remains a significant challenge. This review summarizes recent advances in the field of autoantibodies in SLE.
RECENT FINDINGS
High-throughput technologies and innovative hypothesis have been applied to identify autoantibodies linked to pathogenic pathways in SLE. This work has led to the discovery of functional autoantibodies targeting key components is SLE pathogenesis (e.g. DNase1L3, cytokines, extracellular immunoregulatory receptors), as well as the identification of endogenous retroelements and interferon-induced proteins as sources of autoantigens in SLE. Others have reinvigorated the study of mitochondria, which has antigenic parallels with bacteria, as a trigger of autoantibodies in SLE, and identified faecal IgA to nuclear antigens as potential biomarkers linking gut permeability and microbial translocation in SLE pathogenesis. Recent studies showed that levels of autoantibodies against dsDNA, C1q, chromatin, Sm and ribosomal P may serve as biomarkers of proliferative lupus nephritis, and identified novel autoantibodies to several unique species of Ro52 overexpressed by SLE neutrophils.
SUMMARY
Autoantibodies hold promise as biomarkers of pathogenic mechanisms in SLE.
Topics: Humans; Autoantibodies; Lupus Erythematosus, Systemic; Lupus Nephritis; Autoantigens; Biomarkers
PubMed: 36695053
DOI: 10.1097/BOR.0000000000000922 -
Clinical Reviews in Allergy & Immunology Oct 2022Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued... (Review)
Review
Circulating autoantibodies are a key diagnostic tool in autoimmune hepatitis (AIH), being positive in 95% of the cases if tested according to dedicated guidelines issued by the International Autoimmune Hepatitis Group. They also allow the distinction between type 1 AIH, characterized by positive anti-nuclear and/or anti-smooth muscle antibody, and type 2 AIH, characterized by positive anti-liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibody. Anti-soluble liver antigen is the only AIH-specific autoantibody, and is found in 20-30% of both type 1 and type 2 AIH. Anti-neutrophil cytoplasmic antibody is frequently positive in type 1 AIH, being associated also with inflammatory bowel disease and with primary/autoimmune sclerosing cholangitis. The reference method for autoantibody testing remains indirect immunofluorescence on triple tissue (rodent liver, kidney and stomach), allowing both the detection of the majority of liver-relevant reactivities, including those autoantibodies whose molecular target antigens are unknown. Of note, the current knowledge of the clinical significance of autoantibodies relies on studies based on this technique. However, immunofluorescence requires trained laboratory personnel, is observer-dependent, and lacks standardization, leading to ongoing attempts at replacing this method with automated assays, the sensitivity, and specificity of which, however, require further studies before they can be used as a reliable alternative to immunofluorescence; currently, they may be used as complementary to immunofluorescence.
Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Fluorescent Antibody Technique, Indirect; Hepatitis, Autoimmune; Humans; Immunologic Tests
PubMed: 34491531
DOI: 10.1007/s12016-021-08888-9 -
Neurology(R) Neuroimmunology &... Mar 2020Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in...
OBJECTIVE
Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.
METHODS
A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.
RESULTS
Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.
CONCLUSIONS
Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.
Topics: Adolescent; Algorithms; Autoantibodies; Autoimmune Diseases of the Nervous System; Child; Consensus; Diagnosis, Differential; Encephalitis; Humans; Magnetic Resonance Imaging; Practice Guidelines as Topic
PubMed: 31953309
DOI: 10.1212/NXI.0000000000000663 -
Rheumatic Diseases Clinics of North... Aug 2021B cells exert a prominent contribution to the pathogenesis of systemic lupus erythematosus (SLE). Here, we review the immune mechanisms underlying autoreactive B cell... (Review)
Review
B cells exert a prominent contribution to the pathogenesis of systemic lupus erythematosus (SLE). Here, we review the immune mechanisms underlying autoreactive B cell activation in SLE, focusing on how B cell receptor and Toll-like receptor signals integrate to drive breaks in tolerance to nuclear antigens. In addition, we discuss autoantibody-dependent and autoantibody-independent B cell effector functions during lupus pathogenesis. Finally, we address efforts to target B cells therapeutically in human SLE. Despite initial disappointing clinical trials testing B cell depletion in lupus, more recent studies show promise, emphasizing how greater understanding of underlying immune mechanisms can yield clinical benefits.
Topics: Autoantibodies; B-Lymphocytes; Humans; Lupus Erythematosus, Systemic
PubMed: 34215370
DOI: 10.1016/j.rdc.2021.04.006 -
Clinical and Experimental Rheumatology Feb 2022Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Anti-synthetase syndrome (ASSD) is a heterogeneous autoimmune disease characterised by multi-system involvement with a wide variety of manifestations. Validated classification criteria are necessary to improve recognition and prevent misclassification, especially given the lack of reliable and standardised autoantibody testing. We systematically reviewed the literature to analyse proposed ASSD criteria, characteristics, and diagnostic performance.
METHODS
We searched PubMed and Embase databases (01/01/1984 to 06/11/2018) and the ACR and EULAR meeting abstracts (2017-2018). Sensitivities, specificities, positive, negative likelihood ratios and risk of bias were calculated for ASSD criteria and key variables reported in the literature. We performed meta-analysis when appropriate.
RESULTS
We retrieved 4,358 studies. We found 85 proposed ASSD criteria from a total of 82 studies. All but one study included anti-synthetase autoantibody (ARS) positivity in the ASSD criteria. Most studies required only one ASSD feature plus anti-ARS to define ASSD (n=64, 78%), whereas 16 studies required more than one ASSD variable plus anti-ARS. The only criteria not including anti-ARS positivity required 5 ASSD clinical features. We found limited data and wide variability in the diagnostic performance of each variable and definition proposed in the literature. Given these limitations we only meta-analysed the performance of individual muscle biopsy and clinical variables in diagnosing ASSD, which performed poorly.
CONCLUSIONS
The current ASSD criteria include a variety of serological, clinical, and histological features with wide variability amongst proposed definitions and the performance of these definitions has not been tested. This systematic literature review suggests the need for additional data and consensus-driven classification criteria for ASSD.
Topics: Autoantibodies; Humans; Ligases; Syndrome
PubMed: 35225224
DOI: 10.55563/clinexprheumatol/8xj0b9