Systemic sclerosis, recognized as a prototypical autoimmune disease, is intricately governed by a myriad of autoimmune mechanisms

Systemic sclerosis, recognized as a prototypical autoimmune disease, is intricately governed by a myriad of autoimmune mechanisms. Among these, the major histocompatibility complex (MHC) class I and class II play a pivotal role in the precise presentation of both antigens and autoantigens. Various combinations of MHC I and MHC II alleles have been correlated with the susceptibility to disease onset and the manifestation of specific disease subtypes. Antigen presentation occurs within the context of MHC class I and II molecules, subsequently eliciting responses from CD8 and CD4 T cells, respectively. Co-receptor molecules, such as Ox40L for CD8 T cells, and CD2 and CD247 for CD4 cells, orchestrate proper co-stimulation, culminating in the orchestration of the final immune response. Genetic variability within the interferon system has been extensively documented. Commencing from genes responsible for Toll-like receptor (TLR) encoding, traversing through the intricate signaling cascades mediated by NFκB, and culminating in genetic variations in interferon regulatory factors. A multitude of cytokines are implicated in the pathogenesis of systemic sclerosis, including those operating via the JAK/STAT signaling pathway (e.g., IL-12). Genetic polymorphisms within genes encoding IL-12 receptor, TYK2, and STAT molecules have been associated with the susceptibility to systemic sclerosis development. Similar associations are observed concerning other cytokines such as IL1 (IRAK SNP) and the macrophage migration inhibitory factor (gene promoter of MIF)

Publication

Immunogenetics of Systemic Sclerosis (2024) Olga Gumkowska-Sroka, et al. Genes (Basel). 2024 May;15(5). Figure: F1. Homo sapiens

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