The association of CD18 alleles with anti-myeloperoxidase subtypes of ANCA-associated systemic vasculitides.
Wegener granulomatosis (WG), microscopic polyangiitis (MP), and Churg Strauss syndrome (CSS) are rare systemic autoimmune disorders. Common features are anti-neutrophil cytoplasmic antibodies (ANCA) in patient sera. Whereas WG patients show mainly anti-proteinase 3 ANCA, MP and CSS patients typically 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 adhesion molecules. Here we investigated major adhesion molecules as predisposition factors via common polymorphisms in or in the vicinity of the candidate genes ICAM-1, e-selectin, PLAUR, CD11b, and CD18. A restriction fragment-length 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.
Gencik
M
M
Molekulare Humangenetik, Ruhr-Universität, Bochum, Germany.
Meller
S
S
Borgmann
S
S
Sitter
T
T
Menezes Saecker
A M
AM
Fricke
H
H
Epplen
J T
JT
D000483:Alleles; D000906:Antibodies / Q000145:classification; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000032:analysis*; D018821:CD18 Antigens / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D016177:Macrophage-1 Antigen / Q000235:genetics; D018895:Microsatellite Repeats / Q000235:genetics; D009195:Peroxidase / Q000276:immunology*; D011110:Polymorphism, Genetic; D014657:Vasculitis / Q000276:immunology*
D000906:Antibodies; D019268:Antibodies, Antineutrophil Cytoplasmic; D018821:CD18 Antigens; D019040:E-Selectin; D016177:Macrophage-1 Antigen; D018799:Intercellular Adhesion Molecule-1; D009195:Peroxidase