SYSTEMIC LUPUS ERYTHEMATOSUS: GENETIC COMPONENTS

Abstract

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by the pro-duction of autoantibodies targeting nuclear components, leading to immune complex formation and tissue damage. The clinical manifestations of SLE are highly diverse, complicating disease classification and diagnosis. Genetic studies, including genome-wide association studies (GWAS), have identified numerous genetic risk factors—totalling over 183 loci—associated with SLE susceptibility and its various clinical forms. Epidemiological data indicate a familial aggregation of SLE, with heritability estimates ranging from 44% to 66%, and a notable prevalence of other autoimmune disorders within SLE-affected families. Monogenic forms of SLE, often presenting in childhood, highlight specific genetic defects, particularly within the complement pathway, whereas polygenic SLE typically arises from the interplay between multiple genetic variants and environmental factors. The role of the major histocompatibility complex (MHC) region, particularly HLA-DRB1, is significant across diverse populations, although ethnic-specific variations exist. Non-HLA loci also contribute substantially to SLE risk, with common variants exerting modest effects. Current research endeavors aim to elucidate the functional implications of these genetic variants and to integrate polygenic risk scores (PRS) into clinical practice for better diagnosis, prognosis, and understanding of SLE pathogenesis. Despite advancements, challenges remain in fully characterizing the genetic architecture of SLE and its implications for therapeutic development.