Genetic versus non-genetic drivers of SLE: implications of IRF5 dysregulation in both roads leading to SLE
BJ Barnes - Current Rheumatology Reports, 2019 - Springer
Current Rheumatology Reports, 2019•Springer
Abstract Purpose of Review Systemic 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 that IRF5, a SLE susceptibility gene, has both genetic and non-genetic
contributions to disease pathogenesis. Recent Findings Genetic variants within and around …
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 that IRF5, a SLE susceptibility gene, has both genetic and non-genetic
contributions to disease pathogenesis. Recent Findings Genetic variants within and around …
Purpose of Review
Systemic 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 that IRF5, a SLE susceptibility gene, has both genetic and non-genetic contributions to disease pathogenesis.
Recent Findings
Genetic variants within and around IRF5 robustly associate with SLE risk. In SLE blood cells, IRF5 risk variants associate with elevated IRF5 expression and IFN production. Whether the observed increase in expression is due to risk variants or other disease-associated factors is not clear. Data from Irf5−/− mice backcrossed to multiple models of murine lupus support that IRF5’s role in disease pathogenesis is non-genetic.
Summary
Studies 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.
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