Immunopathogenesis of systemic lupus erythematosus: An update

Abstract

Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by dysregulated immune responses leading to widespread inflammation and damage in various organs. Environmental factors such as infections, hormonal influences and exposure to ultraviolet light can trigger the disease in genetically predisposed individuals. Genome-wide association studies have identified over 100 susceptibility loci linked to immune regulation, interferon (IFN) signaling and antigen presentation in SLE. In addition, rare cases of monogenic lupus have been instrumental in understanding critical underlying disease mechanisms. Several immunological abnormalities contribute to the loss of self-tolerance and the perpetuation of autoimmune responses in SLE. In particular, defective clearance of apoptotic cells due to defective phagocytosis and complement activation leads to accumulation of self-antigens. Dysregulated innate immune responses activate the adaptive immune system, amplifying the inflammatory response with an important role for type I IFNs. Abnormalities in B cell development and activation lead to the production of autoreactive antibodies, forming immune complexes that cause tissue damage. Similarly, disturbances in T-cell compartments, altered regulatory T-cell functions and altered cytokine production, particularly IFN-α, contribute to tissue damage. Understanding of the immunopathogenesis of SLE is evolving rapidly, with ongoing research identifying new molecular pathways and potential therapeutic targets. Future classifications of SLE are likely to be based on underlying biological pathways rather than clinical and serological signs alone. This review aims to provide a detailed update on the most recent findings regarding the immunopathogenesis of SLE, focusing on the variability of biological pathways and the implications for future therapeutic strategies, in particular chimeric antigen receptor T (CAR T) cells.

Keywords: Autoimmune diseases; Immunology; Interferon; Lymphocytes; Pathogenesis; Systemic lupus erythematosus.