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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.

SUBMITTER: Nossent JC 

PROVIDER: S-EPMC3705838 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Susceptibility for Lupus Nephritis by Low Copy Number of the FCGR3B Gene Is Linked to Increased Levels of Pathogenic Autoantibodies.

Nossent Johannes C JC   Becker-Merok Andrea A   Rischmueller Maureen M   Lester Sue S  

Autoimmune diseases 20130620


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  ...[more]

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