Systemic Lupus Erythematosus: Gene Polymorphisms, Epigenetics, Environmental, Hormonal and Nutritional Factors in the Consideration of Personalized Therapy

Author(s): Nejma Wais, Devendra K. Agrawal

Systemic Lupus Erythematosus (SLE) is a chronic illness that can affect many tissues through the production of autoantibodies. A definite etiology has not been conclusively established, but current research points to the influences which include genetic, hormonal and environmental factors. SLE is difficult to treat due to its multifactorial pathogenesis and heterogeneity in clinical manifestations. Current treatment mainly includes anti-malarial medications, glucocorticoids, and biologics, but many patients still struggle in achieving remission. Additionally, there is no definite cure for SLE as of now, which further emphasizes the need for personalized treatment approaches. We analyzed genetic polymorphisms, DNA methylation, and other environmental, hormonal and nutritional factors in the development of SLE. We considered how such factors affect the processes of the disease pathogenesis and may provide insight on targets for potential personalized therapy. In this article, we criticaly reviewed the literature for compelling evidence connecting SLE and specific genes and epigenetic changes. We also explored environmental triggers such as UV exposure, and hormonal influences on their connection to SLE, working toward understanding the disease’s complex nature. A critical evaluation is presented on the use of already accredited biologics in SLE that are beneficial to patients, including anifrolumab and belimumab. The reports on many factors that may influence SLE pathophysiology, along with success with recent biologics/targeted therapies, suggest that precision medicine, tailored to individual genetic and environmental profiles, may hold promise for enhancing remission rates and quality of life for SLE patients. The findings contribute to the field by addressing the need for an integrative approach to SLE treatment and offer more evidence for the potential critical benefit of personalized management strategies that may provide long-term solutions in this challenging and complex disease.