Molecular signatures of intrarenal complement receptorsC3AR1andC5AR1correlate with renal outcome in human lupus nephritis

Abstract

ObjectiveLupus nephritis is one of the most common and serious complications of systemic lupus erythematosus (SLE). Lupus nephritis is a major cause of kidney failure in patients with SLE, attributed to increased morbidity and mortality. The in situ deposition of intrarenal immune complexes promotes the accumulation of inflammatory cells and causes kidney injury.MethodsWe here extracted transcriptome array datasets for expression of complement molecules in human lupus nephritis. Furthermore, we performed gene set enrichment analysis to identify molecular signatures associated with follow-up kidney function in lupus nephritis.ResultsWithin the glomerular compartment, intrarenal mRNA expression levels ofC3AR1(p=0.0333) andC5AR1(p=0.0167) correlated with treatment success reflected by kidney function recovery specifically in class III lupus nephritis, while no such association was observed in class II or class IV lupus nephritis. Interestingly, mRNA expression levels of either glomerularC3AR1orC5AR1resulted in identical gene set and signalling pathways enrichments in human lupus nephritis, including interferon signalling and signalling by interleukins. Direct comparison ofC3AR1andC5AR1confirmed a strong association between glomerular mRNA expression levels of both complement receptors (r=0.8955, p<0.0001).ConclusionsThis study provides additional insights into signalling pathways associated with intrarenal synthesis of complement components in lupus nephritis that might be also affected by targeted therapy of the complement system. These results require confirmation but may contribute to a personalised treatment approach in distinct classes of human lupus nephritis.