996 - Low Copy Number of Fcgamma Receptor 3B Gene Is a Disease Susceptibility and Severity Factor in Primary Sjøgren’s Syndrome

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Johannes C. Nossent1, Maureen Rischmueller2, Andrea Becker-Merok1 and Sue Lester2, 1University of Tromsø, Tromso, Norway, 2Queen Elizabeth Hospital, Adelaide, Australia
Presentation Number: 996

Background/Purpose:  Cross linking of immune-complexes (IC) with the neutrophil specific Fc-gamma receptor 3b (Fcgr3b) initiates IC clearance. IC contribute to the complications of and primary Sjøgren’s syndrome (pSS) and Systemic Lupus Erythematosus (SLE).  Copy number (CN) variation of the Fcgr3b gene alters the Fcgr3b function on the cell membrane and thus influence the clearance of IC. We investigated whether FcgR3b CNV is associated with disease susceptibility and severity in adult patients with pSS.

Method: Cross sectional study of patients with established pSS (n= 174), SLE (n=107) and healthy controls (n= 162). FcGr3b CNV was determined by three different RT-PCR parameter estimations (Ct-, Cy0 and CpD1) and confirmed by the Fcgr2c/Fcgr2a paralog ratio test.  Clinical and serological data were analyzed for their association with FcGr3b CN.

Result: Low FcGr3b CN was significantly more frequent in SLE (OR 4.15, p=0.003) and pSS (OR 2.67, p=0.013) patients than in controls. In pSS patients, low FcGr3b CN was associated with daytime sleepiness, absence of anti-Ro/La and lower levels of RF and IgG. In contrast, low FcGr3b CN was associated with increased levels of antibodies against dsDNA, C1q  and ribosomal P and nephritis in SLE patients. FcGr3b CN did not associate with serum levels of B-cell activating factor in either disease. 

Conclusion: Low FcGr3b CN is a susceptibility factor for both pSS and SLE and associates with more severe disease and pathogenic autoantibodies in SLE and extraglandular features in pSS. The contrasting findings for low FCGr3B CN and levels of anti-dsDNA and anti-Ro/La antibodies indicates selective handling of autoantibodies by Fcgr3b on neutrophils in autoimmune diseases.

Keywords: Fc receptors, Sjogren's syndrome, antibodies and genomics

Disclosure: J. C. Nossent, None; M. Rischmueller, None; A. Becker-Merok, None; S. Lester, None.