Genetic Versus Non-genetic Drivers of SLE: Implications of IRF5 Dysregulation in Both Roads Leading to SLE

AbstractPurpose of ReviewSystemic lupus erythematosus (SLE) is characterized by a breakdown of immune tolerance, resulting in inflammation and tissue destruction. While the primary causes of SLE are still obscure, the disorder is highly heritable. Genetic risk variants, on their own, are rarely causal or fully explain disease pathogenesis. We discuss the possibility thatIRF5, a SLE susceptibility gene, has both genetic and non-genetic contributions to disease pathogenesis.Recent FindingsGenetic variants within and aroundIRF5 robustly associate with SLE risk. In SLE blood cells,IRF5 risk variants associate with elevatedIRF5 expression and IFN production. Whether the observed increase in expression is due to risk variants or other disease-associated factors is not clear. Data fromIrf5−/− mice backcrossed to multiple models of murine lupus support that IRF5 ’s role in disease pathogenesis is non-genetic.SummaryStudies of IRF5 expression and function in genotyped healthy donors will address the question of whether IRF5 dysregulation in SLE is driven by genetic or non-genetic factors.

Source: Current Rheumatology Reports - January 15, 2019 Category: Rheumatology Source Type: research