Susceptibility for lupus nephritis by low copy number of the FCGR3B gene is linked to increased levels of pathogenic autoantibodies

Abstract

Low copy number (CN) of the FCGR3B gene reduces FCGR3B membrane expression on neutrophils and results in clearance of a smaller amount of immune complex. We investigated FCGR3B CN in relation to the clinical phenotype in a Caucasian SLE cohort (n = 107). FCGR3B CN was determined by three different qPCR parameter estimations (Ct-, Cy0, and cpD1) and confirmed by the FCGR2C/FCGR2A paralog ratio test. Clinical and serological data were then analyzed for their association with FCGR3B CN. Low FCGR3B CN (<2) was more frequent in SLE patients than in healthy controls (n = 162) (20% versus 6%, OR 4.15, P = 0.003) and associated with higher disease activity scores (SLEDAI 10.4 versus 6.1, P = 0.03), lupus nephritis (LN) (25 versus 5%, P = 0.03), and increased levels of antibodies against dsDNA (81 versus 37 IU, P = 0.03), C1q (22 versus 6 IU, P = 0.003), and ribosomal P (10 versus 5 IU, P = 0.01). No such associations were seen with antibodies against extractable nuclear antigens or high FCGR3B CN (>2). In multivariate analyses, LN was independently associated with anti-C1q-Ab levels (P = 0.03) and low FCGR3B CN (P = 0.09). We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies.