Genomics of Systemic Lupus Erythematosus Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multi system disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights in-sights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in mono genic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways.