Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by substantial clinical heterogeneity and fluctuating disease activity. Increasing evidence suggests that epigenetic mechanisms, particularly DNA methylation, play a central role in disease development and progression by mediating interactions between genetic susceptibility and environmental influences. This project aims to investigate differential DNA methylation patterns in whole blood from patients with SLE across the course of disease to identify epigenetic changes associated with disease activity, progression, and temporal variation. A second objective is to compare DNA methylation profiles between SLE patients with high and low genetic risk in order to evaluate how inherited susceptibility influences epigenetic regulation and contributes to disease heterogeneity. By integrating genetic and epigenetic data, the study seeks to improve understanding of molecular mechanisms underlying variability in clinical manifestations and immune responses. The project will also predict and analyze human leukocyte antigen (HLA) variants associated with epigenetic variation in SLE patients and investigate their relationships with disease severity, organ involvement, and immunological features. Overall, the study aims to provide new insights into the interplay between genetics and epigenetics in SLE and identify potential biomarkers for disease characterization and precision medicine approaches.