title: 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.
authors.affiliation: Department of Rheumatology, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway ; Department of Rheumatology, University Hospital Northern Norway, P.O. Box 14, 9038 Tromsø, Norway ; Department of Rheumatology, Basil Hetzel Institute, The Queen Elizabeth Hospital, Adelaide, SA 5020, Australia.
authors.forename: Johannes C
authors.initials: JC
authors.lastname: Nossent
authors.forename: Andrea
authors.initials: A
authors.lastname: Becker-Merok
authors.forename: Maureen
authors.initials: M
authors.lastname: Rischmueller
authors.forename: Sue
authors.initials: S
authors.lastname: Lester