Systemic lupus erythematosus (SLE) is a chronic autoimmune disease marked by a highly variable clinical presentation and severity. Its pathophysiology involves an abnormal immune response targeting various tissues, an excess of apoptotic cells, and overproduction of type-I interferon. Genetic studies, including research on monozygotic twins, familial clustering, and genome-wide association studies (GWAS), have identified several risk loci associated with SLE. Recent advances in high-throughput sequencing have revealed a growing number of monogenic defects related to lupus, offering deeper insights into immune tolerance mechanisms.
Monogenic lupus (moSLE) is suspected in patients with early-onset or syndromic lupus, particularly in males or those with a family history of the disease. This review outlines the genetic foundations of monogenic SLE and categorizes it based on disrupted immune pathways, such as defects in the clearance of apoptotic cells or immune complexes, interferonopathies, JAK-STATopathies, TLRopathies, and dysregulations in T and B cells. The increasing recognition of monogenic lupus improves understanding of the disease’s genetic underpinnings and could lead to more targeted therapeutic approaches.
Reference: Tusseau M, Khaldi-Plassart S, Cognard J, et al. Mendelian Causes of Autoimmunity: the Lupus Phenotype. J Clin Immunol. 2024 Apr 15;44(4):99. doi: 10.1007/s10875-024-01696-8. PMID: 38619739.
