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 ( ). 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 ( ) (20% versus 6%, OR 4.15, ) and associated with higher disease activity scores (SLEDAI 10.4 versus 6.1, ), lupus nephritis (LN) (25 versus 5%, ), and increased levels of antibodies against dsDNA (81 versus 37？IU, ), C1q (22 versus 6？IU, ), and ribosomal P (10 versus 5？IU, ). 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 ( ) and low FCGR3B CN ( ). We conclude that the susceptibility for LN in patients with low FCGR3B CN is linked to increased levels of pathogenic autoantibodies. 1. Introduction Systemic lupus erythematosus (SLE) is a severe autoimmune disease that causes a wide spectrum of clinical and serological abnormalities [1]. The characteristic production of antibodies against nuclear and cytoplasmic antigens, which normally are shielded from the immune system, results among others from defective clearance of apoptotic material [2, 3]. Immune complexes containing autoantibodies and nuclear antigens (IC) play a central role in renal inflammation, and depending on their interaction with activating and/or inhibitory FCgR can lead to complement activation, cytokine release, and attraction of neutrophils in Lupus Nephritis (LN), similar to findings in anti-GBM disease [4–6]. Although an abundance of autoantibodies can be detected in sera from SLE patients, only a limited number of autoantibodies are associated with specific disease manifestations such as anti-dsDNA and LN [1]. In contrast, antibodies against other intracellular antigens, such as anti-Ro/La, are in general consistently present in stable titers over prolonged periods of time, independent of underlying disease activity [7]. Copy number variation (CNV) designates the presence of duplications or deletions of DNA segments of considerable size (more than 1？kb) and may be present in as much of 12% of the human genome [8, 9]. CNV is increasingly recognized as an important genetic predisposing factor
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