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FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity

2007; Nature Portfolio; Volume: 39; Issue: 6 Linguagem: Inglês

10.1038/ng2046

1546-1718

Manuela Fanciulli, Penny J. Norsworthy, Enrico Petretto, Rong Dong, Lorraine Harper, Lavanya Kamesh, J. M. Heward, Stephen Gough, Adam J. de Smith, Alexandra I. F. Blakemore, Philippe Froguel, Catherine Owen, Simon H. S. Pearce, Luís Teixeira, Loı̈c Guillevin, Deborah S. Cunninghame Graham, Charles D. Pusey, H. Terence Cook, Timothy J. Vyse, Timothy J. Aitman,

Immunodeficiency and Autoimmune Disorders

Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 × 10−8), microscopic polyangiitis (P = 2.9 × 10−4) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 × 10−3) and France (P = 1.1 × 10−4). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.