B Cells and Autoantibodies in AIRE Deficiency

Wolff, Anette S. B.; Braun, Sarah; Husebye, Eystein S.; Oftedal, Bergithe E.

doi:10.3390/biomedicines9091274

Cited by 4 publications

(4 citation statements)

References 157 publications

(165 reference statements)

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“…Studies performed since 2006 have shown that almost all APS‐1 patients also produce auto‐Abs against type I IFNs from early childhood onward 38,39,89,90 . The detection of these auto‐Abs has even been developed as a diagnostic test for APS‐1 148,149 . About a third of patients with autosomal dominant (AD) APS‐1, caused by dominant‐negative AIRE variants and associated with milder autoimmunity, also develop auto‐Abs against IFN‐α and/or IFN‐ω 150–155 .…”

Section: Genetic Causes Of Auto‐abs Against Type I Ifnsmentioning

confidence: 99%

“…38,39,89,90 The detection of these auto-Abs has even been developed as a diagnostic test for APS-1. 148,149 About a third of patients with autosomal dominant (AD) APS-1, caused by dominant-negative AIRE variants and associated with milder autoimmunity, also develop auto-Abs against IFNα and/or IFNω. [150][151][152][153][154][155] Patients with thymoma, a thymic epithelial tumor, 156 frequently develop T-cell or Ab-mediated autoimmune disease (including late-onset myasthenia gravis, 157 and tissue-specific auto-Abs of the APS-1 spectrum [158][159][160] ).…”

Section: G Ene Ti CC Aus E Sofauto -Abs Ag Ain S T T Ype I Ifn Smentioning

confidence: 99%

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Human autoantibodies neutralizing type I IFNs: From 1981 to 2023

Bastard,

Gervais,

Le Voyer

et al. 2024

Immunological Reviews

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SummaryHuman autoantibodies (auto‐Abs) neutralizing type I IFNs were first discovered in a woman with disseminated shingles and were described by Ion Gresser from 1981 to 1984. They have since been found in patients with diverse conditions and are even used as a diagnostic criterion in patients with autoimmune polyendocrinopathy syndrome type 1 (APS‐1). However, their apparent lack of association with viral diseases, including shingles, led to wide acceptance of the conclusion that they had no pathological consequences. This perception began to change in 2020, when they were found to underlie about 15% of cases of critical COVID‐19 pneumonia. They have since been shown to underlie other severe viral diseases, including 5%, 20%, and 40% of cases of critical influenza pneumonia, critical MERS pneumonia, and West Nile virus encephalitis, respectively. They also seem to be associated with shingles in various settings. These auto‐Abs are present in all age groups of the general population, but their frequency increases with age to reach at least 5% in the elderly. We estimate that at least 100 million people worldwide carry auto‐Abs neutralizing type I IFNs. Here, we briefly review the history of the study of these auto‐Abs, focusing particularly on their known causes and consequences.

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Section: Genetic Causes Of Auto‐abs Against Type I Ifnsmentioning

confidence: 99%

Section: G Ene Ti CC Aus E Sofauto -Abs Ag Ain S T T Ype I Ifn Smentioning

confidence: 99%

Human autoantibodies neutralizing type I IFNs: From 1981 to 2023

Bastard,

Gervais,

Le Voyer

et al. 2024

Immunological Reviews

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“…Since AIRE provides the presentation of 20% to 40% of TSAs in the thymus [ 114 , 115 , 134 ], it can be suggested that the Treg pool of the thymic origins contains the same percent of TCRs specific to AIRE-dependent antigens. It should be noted that due to the formation of the pool of Treg lymphocytes, AIRE indirectly affects the formation of the peripheral repertoire of BCRs [ 156 , 157 ]. It was shown that AIRE deficit led to a condition when the pool of effector CD4 + lymphocytes accumulated numerous TCRs that normally belong to the Treg pool [ 156 , 158 ].…”

Section: The Role Of Aire In the Formation Of Tcr And Bcr Repertoiresmentioning

confidence: 99%

“…It was established that in patients with APECED syndrome or AIRE-deficient mice, the negative selection of self-reactive B-cells was impaired on the periphery, which is normally provided by an inhibiting influence of Treg lymphocytes [ 156 , 159 ]. These patients accumulate mature naïve self-reactive B-cells that produce a wide range of autoantibodies with low specificity to various AIRE-dependent antigens, which is manifested in the clinical picture of patients with APECED syndrome [ 156 , 157 , 159 ].…”

Section: The Role Of Aire In the Formation Of Tcr And Bcr Repertoiresmentioning

confidence: 99%

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

Shevyrev

Tereshchenko

Козлов

et al. 2022

Cells

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It is well known that the most important feature of adaptive immunity is the specificity that provides highly precise recognition of the self, altered-self, and non-self. Due to the high specificity of antigen recognition, the adaptive immune system participates in the maintenance of genetic homeostasis, supports multicellularity, and protects an organism from different pathogens at a qualitatively different level than innate immunity. This seemingly simple property is based on millions of years of evolution that led to the formation of diversification mechanisms of antigen-recognizing receptors and later to the emergence of a system of presentation of the self and non-self antigens. The latter could have a crucial significance because the presentation of nearly complete diversity of auto-antigens in the thymus allows for the “calibration” of the forming repertoires of T-cells for the recognition of self, altered-self, and non-self antigens that are presented on the periphery. The central role in this process belongs to promiscuous gene expression by the thymic epithelial cells that express nearly the whole spectrum of proteins encoded in the genome, meanwhile maintaining their cellular identity. This complex mechanism requires strict control that is executed by several transcription factors. One of the most important of them is AIRE. This noncanonical transcription factor not only regulates the processes of differentiation and expression of peripheral tissue-specific antigens in the thymic medullar epithelial cells but also controls intercellular interactions in the thymus. Besides, it participates in an increase in the diversity and transfer of presented antigens and thus influences the formation of repertoires of maturing thymocytes. Due to these complex effects, AIRE is also called a transcriptional regulator. In this review, we briefly described the history of AIRE discovery, its structure, functions, and role in the formation of antigen-recognizing receptor repertoires, along with other transcription factors. We focused on the phylogenetic prerequisites for the development of modern adaptive immunity and emphasized the importance of the antigen presentation system.

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Autoantibodies in immunodeficiency syndromes: The Janus faces of immune dysregulation

Wang

Walter

2022

Blood Reviews

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B Cells and Autoantibodies in AIRE Deficiency

Cited by 4 publications

References 157 publications

Human autoantibodies neutralizing type I IFNs: From 1981 to 2023

Human autoantibodies neutralizing type I IFNs: From 1981 to 2023

Phylogeny, Structure, Functions, and Role of AIRE in the Formation of T-Cell Subsets

Autoantibodies in immunodeficiency syndromes: The Janus faces of immune dysregulation

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