Fatores genéticos na patogênese do lupus eritematoso sistêmico: uma revisão bibliográfica sobre o gene HLA-G

Abstract

Systemic Lupus Erythematosus (SLE) is a chronic, multisystemic autoimmune disease of multifactorial etiology, characterized by the production of autoantibodies, formation of immune complexes, and systemic inflammation. Its pathophysiology involves the interaction between environmental, immunological, and genetic factors, resulting in failures of immunological self-tolerance. Among the genetic factors associated with the development of SLE, the HLA-G gene stands out. It belongs to the non-classical class I Major Histocompatibility Complex (MHC) and plays important immunomodulatory and immunosuppressive roles essential for maintaining immune tolerance. Alterations in HLA-G expression and its polymorphisms, especially in the 3’UTR region, may influence mRNA stability, serum protein levels, and immune response regulation, favoring the persistence of autoreactive cells and disease progression. This study aimed to review the scientific literature regarding the relationship between genetic factors, with emphasis on the HLA-G gene, and the pathogenesis of SLE. This is a narrative literature review based on scientific articles published in PubMed, SciELO, and BVS databases between 2008 and 2026, in Portuguese and English. The analyzed studies demonstrate that HLA-G plays a relevant role in the modulation of the immune response through interactions with inhibitory receptors expressed on immune cells, such as ILT2, ILT4, and KIR2DL4. Furthermore, evidence suggests that specific HLA-G polymorphisms may be associated with susceptibility, clinical activity, and severity of SLE. Therefore, HLA-G can be considered an important immunogenetic biomarker in the pathophysiology of SLE, contributing to the understanding of autoimmune mechanisms and potentially assisting in diagnosis, prognosis, and the development of targeted therapies.