Systemic lupus erythematosus (SLE) is a relapsing, multisystem autoimmune disease driven by autoantibodies and immune-complex deposition that inflame and injure organs (kidneys, central nervous system, joints, skin). Current care relies largely on nonspecific immunosuppression with substantial toxicity; approximately 20% to 30% fail to achieve remission and about one-third relapse. This narrative review integrates clinical and experimental data on SLE immunopathophysiology.
Susceptibility and expression reflect genetics, hormones, and environmental triggers. Mechanistically, skewing toward M1 macrophages, neutrophil NETosis, complement dysregulation, and plasmacytoid dendritic cell TLR7/9–driven IFN-I amplify inflammation; epigenetic changes sustain activation. Adaptive immunity shows Th1/Th17/Tfh expansion with impaired Tregs and pathogenic B-cell/plasmablast responses, yielding a broad autoantibody repertoire. Gut dysbiosis further biases Th17 and fuels systemic autoimmunity—together forming a reinforcing cycle that underlies disease activity and organ damage.
Reference: Ahmed A, Li S, Yu JJ, Shao WH. Immunopathogenesis of Systemic Lupus Erythematosus: Interplay of Innate and Adaptive Immunity, Microbiome Dysbiosis, and Emerging Therapeutic Targets. Pathophysiology. 2025;32(4):61. doi: 10.3390/pathophysiology32040061.
