Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.

PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is a severe autoimmune/inflammatory disease. Patients with juvenile disease-onset and those of non-European ancestry are most severely affected. While the exact pathophysiology remains unknown, common and rare gene variants in the context of environmental exposure and epigenetic alterations are involved. This manuscript summarizes the current understanding of genetic and epigenetic contributors to SLE risk, manifestations and outcomes.

RECENT FINDINGS: Though SLE is a mechanistically complex disease, we are beginning to understand the impact of rare and common gene variants on disease expression and associated outcomes. Recent trans -ancestral and multigenerational studies suggest that differential genetic and environmental impacts shape phenotypic variability between age-groups and ancestries. High genetic burden associates with young age at disease-onset, organ involvement, and severity. Additional epigenetic impact contributes to disease-onset and severity, including SLE-phenotypes caused by rare single gene variants. Studies aiming to identify predictors of organ involvement and disease outcomes promise future patient stratification towards individualized treatment and care.

SUMMARY: An improved understanding of genetic variation and epigenetic marks explain phenotypic differences between age-groups and ancestries, promising their future exploitation for diagnostic, prognostic and therapeutic considerations.