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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 -
Trends in Molecular Medicine Jan 2023Autoantibodies targeting brain antigens can mediate a wide range of neurological symptoms ranging from epileptic seizures to psychosis to dementia. Although earlier... (Review)
Review
Autoantibodies targeting brain antigens can mediate a wide range of neurological symptoms ranging from epileptic seizures to psychosis to dementia. Although earlier experimental work indicated that autoantibodies can be directly pathogenic, detailed studies on disease mechanisms, biophysical autoantibody properties, and target interactions were hampered by the availability of human material and the paucity of monospecific disease-related autoantibodies. The emerging generation of patient-derived monoclonal autoantibodies (mAbs) provides a novel platform for the detailed characterization of immunobiology and autoantibody pathogenicity in vitro and in animal models. This Feature Review focuses on recent advances in mAb generation and discusses their potential as powerful scientific tools for high-resolution imaging, antigenic target identification, atomic-level structural analyses, and the development of antibody-selective immunotherapies.
Topics: Animals; Humans; Autoantibodies
PubMed: 36280535
DOI: 10.1016/j.molmed.2022.09.011 -
Current Cardiology Reports Nov 2020The role of autoantibodies in arrhythmogenesis has been the subject of research in recent times. This review focuses on the rapidly expanding field of... (Review)
Review
PURPOSE OF REVIEW
The role of autoantibodies in arrhythmogenesis has been the subject of research in recent times. This review focuses on the rapidly expanding field of autoantibody-mediated cardiac arrhythmias.
RECENT FINDINGS
Since the discovery of cardiac autoantibodies more than three decades ago, a great deal of effort has been devoted to understanding their contribution to arrhythmias. Different cardiac receptors and ion channels were identified as targets for autoantibodies, the binding of which either initiates a signaling cascade or serves as a biomarker of underlying remodeling process. Consequently, the wide spectrum of heart rhythm disturbances may emerge, ranging from atrial to ventricular arrhythmias as well as conduction diseases, irrespective of concomitant structural heart disease or manifest autoimmune disorder. The time has come to acknowledge autoimmune cardiac arrhythmias as a distinct disease entity. Establishing the autoantibody profile of patients will help to develop novel treatment approaches for patients.
Topics: Arrhythmias, Cardiac; Autoantibodies; Autoimmune Diseases; Heart Conduction System; Humans; Ion Channels
PubMed: 33241446
DOI: 10.1007/s11886-020-01430-x -
Movement Disorders : Official Journal... Sep 2018An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins... (Review)
Review
An increasing number of movement disorders are associated with autoantibodies. Many of these autoantibodies target the extracellular domain of neuronal surface proteins and associate with highly specific phenotypes, suggesting they have pathogenic potential. Below, we describe the phenotypes associated with some of these commoner autoantibody-mediated movement disorders, and outline increasingly well-established mechanisms of autoantibody pathogenicity which include antigen downregulation and complement fixation. Despite these advances, and the increasingly robust evidence for improved clinical outcomes with early escalation of immunotherapies, the underlying cellular immunology of these conditions has received little attention. Therefore, here, we outline the likely roles of T cells and B cells in the generation of autoantibodies, and reflect on how these may guide both current immunotherapy regimes and our future understanding of precision medicine in the field. In addition, we summarise potential mechanisms by which these peripherally-driven immune responses may reach the central nervous system. We integrate this with the immunologically-relevant clinical observations of preceding infections, tumours and human leucocyte antigen-associations to provide an overview of the therapeutically-relevant underlying adaptive immunology in the autoantibody-mediated movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Topics: Animals; Autoantibodies; Humans; Immunotherapy; Male; Movement Disorders; Nerve Tissue Proteins
PubMed: 30218501
DOI: 10.1002/mds.27446 -
Frontiers in Immunology 2018Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of... (Review)
Review
Autoimmune blistering diseases are characterized by autoantibodies against structural adhesion proteins of the skin and mucous membranes. Extensive characterization of their autoantibody targets has improved understanding of pathogenesis and laid the basis for the study of antigens/epitopes diversification, a process termed epitope spreading (ES). In this review, we have reported and discussed ES phenomena in autoimmune bullous diseases and underlined their functional role in disease pathogenesis. A functional ES has been proposed: (1) in bullous pemphigoid patients and correlates with the initial phase of the disease, (2) in pemphigus vulgaris patients with mucosal involvement during the clinical transition to a mucocutaneous form, (3) in endemic pemphigus foliaceus, underlining its role in disease pathogenesis, and (4) in numerous cases of disease transition associated with an intermolecular diversification of immune response. All these findings could give useful information to better understand autoimmune disease pathogenesis and to design antigen/epitope specific therapeutic approaches.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Epitopes; Humans; Skin Diseases, Vesiculobullous
PubMed: 29719538
DOI: 10.3389/fimmu.2018.00779 -
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 -
Medecine Sciences : M/S 2005Autoimmune response is diverse. This diversity is thought not to take place at the beginning of the autoimmune process but to occur as the disease evolves. It is mainly... (Review)
Review
Autoimmune response is diverse. This diversity is thought not to take place at the beginning of the autoimmune process but to occur as the disease evolves. It is mainly the consequence of the so-called epitope-spreading phenomenon and of the cross-reactivity of antibodies. Analysing autoantibody repertoire constitutes a powerful means to understand physiopathological processes at work in various diseases, mainly autoimmune diseases. In particular this analysis opens the way to precisely identify autoantigens and their changes in various pathological situations, and allows providing new biological markers in chronic inflammatory diseases. New methodologies have recently emerged for the analysis of the autoantibody repertoire in a given individual. They propose diagnostic approaches no more related upon few markers but founded upon analysis of global changes of the antibody repertoire. They belong to methodologies called target-oriented proteomics. Their common feature is to isolate autoantigens by means of affinity chromatography based upon antibody/antigen reactions. Autoantibodies to be studied interact with a protein substratum susceptible to include autoantibody targets. These interactions take place on solid macro- or microsurfaces, i.e. membrane filters or chips. Several strategies can be used for locating the specific autoantibody/autoantigen complexes and for identifying behind autoantigens. In this paper three approaches, namely, the recombinant protein chips, the SELDI techniques and the 2-D gel electrophoresis linked to mass spectrometry are described and compared.
Topics: Autoantibodies; Autoantigens; Humans; Models, Immunological; Proteomics
PubMed: 16115463
DOI: 10.1051/medsci/2005218-9759 -
Bioanalysis May 2016Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed... (Review)
Review
Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed assays based on antigen arrays hold a great potential and provide possibilities to analyze hundreds of body fluid samples for their reactivity pattern against thousands of antigens in parallel. Here, we provide an overview of the available technologies for producing antigen arrays, highlight some of the technical and methodological considerations and discuss their applications as discovery tools. Together with recent studies utilizing antigen arrays, we give an overview on how the different types of antigen arrays have and will continue to deliver novel insights into autoimmune diseases among several others.
Topics: Animals; Autoantibodies; Biomarkers; Humans; Protein Array Analysis; Proteomics
PubMed: 27097564
DOI: 10.4155/bio.16.31 -
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 -
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