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Antibodies in Autoimmune Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (15 January 2023) | Viewed by 8275

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Prof. Dr. Tímea Berki

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Guest Editor

Department of Immunology and Biotechnology, Medical School, University of Pécs, 7624 Pécs, Hungary
Interests: tissue culturing; hybridoma technology; monoclonal antibody production and characterization

Prof. Dr. Péter Balogh

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Guest Editor

Department of Immunology and Biotechnology, University of Pécs Medical School, 7624 Pécs, Hungary
Interests: lymphoid; animal models of autoimmunity; Immunology

Special Issue Information

Dear Colleagues,

In a healthy individual the immune system can distinguish between self and non-self antigens, and respond accordingly with an active immune response against external pathogens and modified self-structures, but will protect normal self-structures and establish tolerance against these. There are several components of the tolerance induction, including natural autoantibodies, regulatory T and B cells, and the selection of lymphocytes in the primary lymphoid organs.

Autoimmune diseases arise from unregulated immune responses against self-molecules. Their development is influenced by genetic and environmental factors, age and hormones. There are more than 80 types of autoimmune diseases mediated or marked by autoantibodies, which can be classified into systemic or organ-specific diseases. Pathogenic autoantibodies contribute to the disease mechanism in a number of ways, including the deposition of immune complexes, the induction of inflammation, and the stimulation or inhibition of receptor or enzyme functions, thus affecting cellular signaling or metabolism. The detection of new disease-related autoantibodies can help in the diagnosis of the disease, or can be a marker of the efficacy of the therapy. In addition, understanding the biology of autoimmunity-linked B-cell subsets and their roles through animal models may pave the way towards more efficient therapy, coupled with less-severe side effects.

This Special Issue aims to present the latest research results and new views on the cellular and molecular aspects of processes resulting in autoantibody production, autoimmune B-cell formation and their relevance to autoimmune diseases. We aim to bring together exciting new developments in this field. Both original research articles and comprehensive reviews are welcomed.

Prof. Dr. Tímea Berki
Prof. Dr. Péter Balogh
Guest Editors

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Keywords

autoimmune diseases
autoantibodies
autoimmune B-cell
autoimmunity-linked B-cell subsets
animal models
cellular signaling/metabolism
targeted therapies

Published Papers (3 papers)

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Research

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11 pages, 1718 KiB

Open AccessArticle

Natural and Pathological Autoantibodies Show Age-Related Changes in a Spontaneous Autoimmune Mouse (NZB) Model

by Szonja Gál, Erzsébet Gajdócsi, Esam Khanfar, Katalin Olasz, Diána Simon, Péter Balogh, Tímea Berki, Péter Németh and Ferenc Boldizsár

Int. J. Mol. Sci. 2023, 24(12), 9809; https://doi.org/10.3390/ijms24129809 - 06 Jun 2023

Cited by 1 | Viewed by 1066

Abstract

The natural autoantibody (natAAb) network is thought to play a role in immune regulation. These IgM antibodies react with evolutionary conserved antigens; however, they do not lead to pathological tissue destruction as opposed to pathological autoantibodies (pathAAb). The exact relation between the natAAbs and pathAAbs is still not completely understood; therefore, in the present study, we set out to measure nat- and pathAAb levels against three conserved antigens in a spontaneous autoimmune disease model: the NZB mouse strain which develops autoimmune hemolytic anemia (AIHA) from six months of age. There was an age dependent increase in the natAAb levels in the serum against Hsp60, Hsp70, and the mitochondrial citrate synthase until 6–9 months of age, followed by a gradual decrease. The pathological autoantibodies appeared after six months of age, which corresponded with the appearance of the autoimmune disease. The changes in nat/pathAAb levels were coupled with decreasing B1- and increasing plasma cell and memory B cell percentages. Based on this, we propose that there is a switch from natAAbs towards pathAAbs in aged NZB mice. Full article

(This article belongs to the Special Issue Antibodies in Autoimmune Diseases)

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20 pages, 3711 KiB

Open AccessArticle

Complexity of the Immune Response Elicited by Different COVID-19 Vaccines, in the Light of Natural Autoantibodies and Immunomodulatory Therapies

by Katalin Böröcz, Ágnes Kinyó, Diana Simon, Szabina Erdő-Bonyár, Péter Németh and Timea Berki

Int. J. Mol. Sci. 2023, 24(7), 6439; https://doi.org/10.3390/ijms24076439 - 29 Mar 2023

Cited by 4 | Viewed by 1469

Abstract

Despite the abundance of data on the COVID-19 vaccine-induced immune activation, the impact of natural autoantibodies (nAAbs) on these processes is less well defined. Therefore, we investigated potential connections between vaccine efficacy and nAAb levels. We were also interested in the impact of immunomodulatory therapies on vaccine efficacy. Clinical residual samples were used for the assessment of the COVID-19 vaccine-elicited immune response (IR) (n=255), as well as for the investigation of the immunization-associated expansion of the nAAb pool (n=185). In order to study the potential interaction between immunomodulatory therapies and the vaccine-induced IR, untreated, healthy individuals and patients receiving anti-TNFα or anti-IL-17 therapies were compared (n total =45). In-house ELISAs (anticitrate synthase, anti-HSP60 and-70) and commercial ELISAs (anti-SARS-CoV-2 ELISAs IgG, IgA, NeutraLISA and IFN-γ release assay ‘IGRA’) were applied. We found significant differences in the IR given to different vaccines. Moreover, nAAb levels showed plasticity in response to anti-COVID-19 immunization. We conclude that our findings may support the theorem about the non-specific beneficial ‘side effects’ of vaccination, including the broadening of the nAAb repertoire. Considering immunomodulation, we suggest that anti-TNFα and anti-IL17 treatments may interfere negatively with MALT-associated IR, manifested as decreased IgA titers; however, the modest sample numbers of the herein presented model might be a limiting factor of reaching a more comprehensive conclusion. Full article

(This article belongs to the Special Issue Antibodies in Autoimmune Diseases)

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Review

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20 pages, 3602 KiB

Open AccessReview

Anti-Islet Autoantibodies in Type 1 Diabetes

by Eiji Kawasaki

Int. J. Mol. Sci. 2023, 24(12), 10012; https://doi.org/10.3390/ijms241210012 - 11 Jun 2023

Cited by 9 | Viewed by 4980

Abstract

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. Full article

(This article belongs to the Special Issue Antibodies in Autoimmune Diseases)

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