Genetics of human lupus nephritis

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disease characterized by immune complex formation with multi-organ manifestations. Lupus nephritis (LN) is one of the most severe types of organ damage in SLE, and it clearly contributes to increased morbidity and mortality due to SLE. LN occurs more frequently and is more severe in non-European ancestral backgrounds, although the cause of this disparity remains largely unknown. Genetic factors play an important role in the pathogenesis of SLE. Although many SLE susceptibility genes have been identified, the genetic basis of LN is not as well understood. While some of the established general SLE susceptibility genes are associated with LN, recent discoveries highlight a number of genes with renal functions that are specifically associated with LN. Some of these genes associated with LN help to explain the disparity in the prevalence of nephritis between individuals with SLE, and also partially explain differences in LN between ancestral backgrounds. Moreover, not only the gene mutations, but also post-translational modifications seem to play important roles in the pathogenesis of LN. Overall it seems likely that a combination of general SLE susceptibility genes cooperate with LN specific risk genes to result in the genetic propensity for LN. In this review, we will outline the genetic contribution to LN and describe possible roles of LN susceptibility genes.