Sero-Reactivity to Microbial Components in Crohn's Disease Is Associated with Disease Severity and Progression, but not NOD2/CARD15 Genotype

作者：Ian D. Arnott, Carol J. Landers, Elaine Nimmo, Hazel E. Drummond, B Smith, Stephan R. Targan, Jack Satsangi · 发表于：The American Journal of Gastroenterology · 年份：2004 · DOI：10.1111/j.1572-0241.2004.40417.x · 被引用次数：232 · 研究领域：Inflammatory Bowel Disease、Autoimmune and Inflammatory Disorders、Neutrophil, Myeloperoxidase and Oxidative Mechanisms

BACKGROUND AND AIMS: Antibodies directed against the porin protein C of Escherichia coli (anti-OmpC) and Pseudomonas fluorescens (anti-I2) have recently been described in Crohn's disease (CD). Those directed against Saccharomyces cerevisiae (ASCA) and the perinuclear component of neutrophils (pANCA) have been more widely studied and may be of diagnostic importance. We aimed to assess the frequency of anti-OmpC, anti-I2, ASCA, and pANCA, in an independent Scottish CD cohort, establish phenotypic associations, and compare with a U.S. cohort. METHODS: One hundred and forty-two well-characterized CD patients (76 females, median age 39 yr (17-88)) were studied. CD was classified by the Vienna classification. Sera were assayed for anti-OmpC, anti-I2, ASCA, and pANCA. Allele specific primers were used for NOD2/CARD15 genotyping. RESULTS: Anti-OmpC, anti-I2, ASCA, and pANCA were present in sera from 37%, 52%, 39%, and 14% of CD patients, respectively. Multivariate analysis demonstrated independent associations of anti-OmpC to be progression of disease type (p= 0.005) and long disease duration (p= 0.002), and those of anti-I2 to be long disease duration (p= 0.002) and the need for surgery (p= 0.033). ASCA were associated with disease progression (p < 0.001). When the presence and magnitude of all antibody responses were considered, reactivity to microbial components was associated with long disease duration (p < 0.001), progression of disease type (p < 0.001), penetrating disease (p= ...