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The Journal of Applied Laboratory... Jan 2022Dermatologic diseases with autoantibodies were recognized early as autoimmunity became accepted as a pathogenic immunologic concept. Laboratory testing to identify... (Review)
Review
BACKGROUND
Dermatologic diseases with autoantibodies were recognized early as autoimmunity became accepted as a pathogenic immunologic concept. Laboratory testing to identify disease-defining autoantibodies and investigate their role in pathophysiology has evolved since.
CONTENT
Blistering dermatologic diseases, profiled by autoantibody production, target epithelial components critical in cell-cell and cell-matrix adhesion, resulting in epithelial separation and other characteristic features of the disorders. This review covers the clinical indications for dermatologic disease-related autoantibody testing, the specifics of procuring specimens to test, the available diagnostic tests, and information provided by the testing. Atypical, uncharacteristic, and less well-known clinical and autoantibody profiles as well as several of the many future prospects for expansion of the testing applications are elaborated on in the online Data Supplement.
SUMMARY
Autoantibody-associated dermatologic diseases are acquired immunologic disorders that have considerable clinical implications affecting essential barrier functions of skin and mucous membranes and causing discomfort, including pain and pruritus. Certain of the diseases can have life-threatening manifestations, and treatments can have significant side-effects. The skin diseases may presage other clinical associations that are important to recognize and treat. Laboratory testing aids in the diagnosis of these diseases through identification of the autoantibodies and is essential for prompt and precise knowledge of the disease type for prognosis, further clinical evaluations, and treatment decisions.
Topics: Autoantibodies; Humans; Pemphigoid, Bullous; Skin
PubMed: 34996089
DOI: 10.1093/jalm/jfab147 -
The Journal of Allergy and Clinical... Nov 2022The presence of autoreactive antibodies is a hallmark of many autoimmune diseases. The effector functions of (auto)antibodies are determined by their constant domain,... (Review)
Review
The presence of autoreactive antibodies is a hallmark of many autoimmune diseases. The effector functions of (auto)antibodies are determined by their constant domain, which defines the antibody isotype and subclass. The most prevalent isotype in serum is IgG, which is often the only isotype used in diagnostic testing. Nevertheless, autoantibody responses can have their own unique isotype/subclass profile. Because comparing autoantibody isotype profiles may yield new insights into disease pathophysiology, here we summarize the isotype/subclass profiles of the most prominent autoantibodies. Despite substantial variation between (and within) autoantibody responses, this unprecedented comparison shows that autoantibodies share distinctive isotype patterns across different diseases. Although most autoantibody responses are dominated by IgG (and mainly IgG1), several specific diseases are characterized by a predominance of IgG4. In other diseases, IgE plays a key role. Importantly, shared features of autoantibody isotype/subclass profiles are seen in clinically unrelated diseases, suggesting potentially common trajectories in response evolution, disease pathogenesis, and treatment response. Isotypes beyond IgG are scarcely investigated in many autoantibody responses, leaving substantial gaps in our understanding of the pathophysiology of autoimmune diseases. Future research should address isotype/subclass profiling in more detail and incorporate autoantibody measurements beyond total IgG in disease models and clinical studies.
Topics: Humans; Autoantibodies; Immunoglobulin G; Autoimmune Diseases
PubMed: 36336400
DOI: 10.1016/j.jaci.2022.05.023 -
Frontiers in Immunology 2023Mutations in the recombination activating gene 1 () and in humans are associated with a broad spectrum of clinical phenotypes, from severe combined immunodeficiency to... (Review)
Review
Mutations in the recombination activating gene 1 () and in humans are associated with a broad spectrum of clinical phenotypes, from severe combined immunodeficiency to immune dysregulation. Partial (hypomorphic) RAG deficiency (pRD) in particular, frequently leads to hyperinflammation and autoimmunity, with several underlying intrinsic and extrinsic mechanisms causing a break in tolerance centrally and peripherally during T and B cell development. However, the relative contributions of these processes to immune dysregulation remain unclear. In this review, we specifically focus on the recently described tolerance break and B cell abnormalities, as well as consequent molecular and cellular mechanisms of autoantibody production in patients with pRD.
Topics: Humans; Homeodomain Proteins; Severe Combined Immunodeficiency; Autoimmunity; Phenotype; Autoantibodies
PubMed: 37475856
DOI: 10.3389/fimmu.2023.1155380 -
The Lancet. Rheumatology Dec 2023Increased research over the past 30 years has greatly improved the understanding of the pathophysiological mechanisms and clinical aspects of autoantibody-positive... (Review)
Review
Increased research over the past 30 years has greatly improved the understanding of the pathophysiological mechanisms and clinical aspects of autoantibody-positive rheumatoid arthritis, resulting in improved management and outcomes. In contrast, the subset of rheumatoid arthritis that does not have autoantibodies (such as rheumatoid factor and anti-citrullinated protein autoantibodies) remains less well defined in its pathogenic mechanisms. Autoantibody-negative rheumatoid arthritis continues to pose diagnostic challenges, might respond differently to therapies, and appears to be burdened with different comorbidities and outcomes. The clear separation of rheumatoid arthritis according to serotypes is still a subject of uncertainty and controversy, and studies specifically focused on comparing rheumatoid arthritis and rheumatoid arthritis-like arthritides that do not have autoantibodies remain scarce. The purpose of this Review is to summarise the peculiarities that make autoantibody-negative rheumatoid arthritis different from its autoantibody-positive counterpart, with the aim of generating debate and stimulating further research on this challenging condition.
Topics: Humans; Autoantibodies; Rheumatologists; Arthritis, Rheumatoid; Rheumatoid Factor; Anti-Citrullinated Protein Antibodies
PubMed: 38251565
DOI: 10.1016/S2665-9913(23)00242-4 -
Advances in Clinical Chemistry 2024Idiopathic inflammatory myopathies (IIM), generally referred to as myositis is a heterogeneous group of diseases characterized by muscle inflammation and/or skin... (Review)
Review
Idiopathic inflammatory myopathies (IIM), generally referred to as myositis is a heterogeneous group of diseases characterized by muscle inflammation and/or skin involvement, diverse extramuscular manifestations with variable risk for malignancy and response to treatment. Contemporary clinico-serologic categorization identifies 5 main clinical groups which can be further stratified based on age, specific clinical manifestations and/or risk for cancer. The serological biomarkers for this classification are generally known as myositis-specific (MSAs) and myositis-associated antibodies. Based on the use of these antibodies, IIM patients are classified into anti-synthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, inclusion body myositis, and overlap myositis. The current classification criteria for IIM requires clinical findings, laboratory measurements, and histological findings of the muscles. However, the use MSAs and myositis-associated autoantibodies as an adjunct for disease evaluation is thought to provide a cost-effective personalized approach that may not only guide diagnosis but aid in stratification and/or prognosis of patients. This review provides a comprehensive overview of contemporary autoantibodies that are specific or associated myositis. In addition, it highlights possible pathways for the detection and interpretation of these antibodies with limitations for routine clinical use.
Topics: Humans; Autoantibodies; Myositis; Biomarkers
PubMed: 38762242
DOI: 10.1016/bs.acc.2024.04.001 -
Current Opinion in Rheumatology Nov 2018The aim of this study was to provide the most recent evidence on clinical utility of myositis-specific autoantibodies (MSAs) in the management of patients with myositis. (Review)
Review
PURPOSE OF REVIEW
The aim of this study was to provide the most recent evidence on clinical utility of myositis-specific autoantibodies (MSAs) in the management of patients with myositis.
RECENT FINDINGS
In the last few years, several evidences have emerged on the clinical and pathogenetic role of established and novel MSA. Antisynthetase antibodies represent a reliable biomarker for pulmonary involvement also in patients with connective tissue diseases other than myositis. Antisignal recognition particle and antihydroxy-3-methylglutaryl coenzyme A reductase autoantibodies are able to induce complement-dependent muscle damage. Dermatomyositis-specific antibodies are useful indicators of clinical diversity. The pivotal role of antitranscription intermediary factor 1γ autoimmune response in adult-age paraneoplastic dermatomyositis has been further asserted. AnticN1A and antifour-and-a-half LIM protein 1 antibodies are newly conceived myositis-related antibody specificities, which can contribute to patients' stratification into more homogeneous groups.
SUMMARY
Distinct autoantibody-associated clinical phenotypes can be predicted by extended MSA testing in serum. Standardization and validation of MSA laboratory detection methods is strongly recommended for better supporting myositis diagnosis, management and prognosis definition.
Topics: Autoantibodies; Autoimmunity; Humans; Myositis; Prognosis
PubMed: 30234722
DOI: 10.1097/BOR.0000000000000548 -
International Journal of Molecular... Feb 2020Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes,... (Review)
Review
Autoantibodies encountered in patients with systemic rheumatic diseases bear clinical significance as a biomarker to help or predict diagnosis, clinical phenotypes, prognosis, and treatment decision-making. Furthermore, evidence has accumulated regarding the active involvement of disease-specific or disease-associated autoantibodies in the pathogenic process beyond simple association with the disease, and such knowledge has become essential for us to better understand the clinical value of autoantibodies as a biomarker. This review will focus on the current update on the autoantibodies of four rheumatic diseases (rheumatoid arthritis, myositis, systemic sclerosis, and anti-neutrophil cytoplasmic antibody associated vasculitis) where there has been a tremendous progress in our understanding on their biological effects and clinical use.
Topics: Antibodies, Antineutrophil Cytoplasmic; Autoantibodies; Biomarkers; Humans; Rheumatic Diseases
PubMed: 32085664
DOI: 10.3390/ijms21041382 -
Frontiers in Immunology 2023The Danger Model predicts that there are some molecules that no immune system can ever be fully tolerant of, namely proteins that are only transiently expressed during...
The Danger Model predicts that there are some molecules that no immune system can ever be fully tolerant of, namely proteins that are only transiently expressed during times of stress, infection, or injury. Among these are the danger/alarm signals themselves. Accordingly, a fleeting autoantibody response to danger signals is expected during times when they are released. Depending on context, these autoantibodies may serve beneficial "housekeeping" functions by removing surplus danger signals from the circulation or, conversely, create an immunodeficiency. Here, we will focus on the Type 1 Interferons as examples of foreseeable targets for a transient autoantibody response, but the principles outlined should hold for other danger-associated molecules as well.
Topics: Immune System; Autoantibodies; Interferon Type I
PubMed: 36742299
DOI: 10.3389/fimmu.2023.1046300 -
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 -
Current Opinion in Organ Transplantation Aug 2016The review analyzes the current biomarkers used in monitoring pancreas transplant, from the simple and time-tested, to more sophisticated, including markers of allo- and... (Review)
Review
PURPOSE OF REVIEW
The review analyzes the current biomarkers used in monitoring pancreas transplant, from the simple and time-tested, to more sophisticated, including markers of allo- and autoimmunity, that are likely to play a larger role in future studies.
RECENT FINDINGS
Evaluation of alloimmunity includes serum levels of donor-specific antibody, and, ultimately, pancreas transplant biopsies with C4d staining. Our center has focused on markers of autoimmunity, including assessment of autoantibodies and autoreactive T cells. We have found that conversion of autoantibodies (including GAD65, IA-2, and ZnT8), or the development of a new positive autoantibody, particularly ZnT8, are associated with type 1 diabetes (T1D) recurrence in the pancreas transplant. Autoreactive T cells have also been identified in the peripheral blood, pancreas transplant and peripancreas transplant-lymph nodes, that have the potential to mediate human β/islet cell destruction in vivo.
SUMMARY
The monitoring of pancreas transplant biomarkers, particularly those associated with autoimmunity, has led to new insights into the pathogenesis of T1D. Progress in the elucidation of mechanisms of autoimmunity may lead to novel therapeutic approaches to both T1D recurrence of the pancreas transplant and perhaps also new onset T1D.
Topics: Autoantibodies; Biomarkers, Tumor; Humans; Pancreas Transplantation
PubMed: 27348473
DOI: 10.1097/MOT.0000000000000333