Association Analysis of the MHC in Lupus Nephritis

Abstract

Lupus nephritis (LN) is one of the most prevalent and serious complications of SLE, with significant effects on patient and renal survival. Although a large number of genetic variants associated with SLE have been identified, biomarkers that correlate with LN are extremely limited. In this study, we performed a comprehensive sequencing analysis of the whole MHC region in 1331 patients with LN and 1296 healthy controls and validated the independent associations in another 950 patients with LN and 1000 controls. We discovered five independent risk variants for LN within the MHC region, including HLA-DR beta 1 amino acid 11 (P-omnibus < 0.001), HLA-DQ beta 1 amino acid 45 (P < 0.001; odds ratio, 0.58; 95% confidence interval, 0.52 to 0.65), HLA-A amino acid 156 (P-omnibus < 0.001), HLA-DP beta 1 amino acid 76 (P-omnibus < 0.001), and a missense variant in PRRC2A (rs114580964; P < 0.001; odds ratio, 0.38; 95% confidence interval, 0.30 to 0.49) at genome-wide significance. These data implicate aberrant peptide presentation by MHC classes 1 and 2 molecules and sex hormone modulation in the development of LN.