The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides

Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg Strau ss syndrome (CSS) are rare systemic autoimmune disorders. Common features a re anti-neutrophil cytoplasmic antibodies (ANCA) in patient sera. Whereas W G; patients show mainly anti-proteinase 3 ANCA, MP and CSS patients typical ly present anti-myeloperoxidase (MPO) ANCA. ANCA play an important role in the pathogenesis in the vessel wall by activating polymorphonuclear cells ( PMN) and increased adhesivity between PMN and endothelial cells via adhesio n molecules. Here we investigated major adhesion molecules as predispositio n factors via common polymorphisms in or in the vicinity of the candidate g enes ICAM-1, e-selectin, PLAUR, CD11b, and CD18. A restriction fragment-len gth polymorphism in exon 11 of the CD18 gene was associated with MPO-ANCA() systemic vasculitis. Our data indicate that a common variant of the CD18 gene confers increased risk for CSS and MP, supporting that genetic factors are involved in the etiology and pathogenesis of ANCA-associated systemic vasculitides. (C) 2000 Academic Press.