Original Contribution
The American Journal of Gastroenterology (2004) 99, 2376–2384; doi:10.1111/j.1572-0241.2004.40417.x
Sero-Reactivity to Microbial Components in Crohn's Disease Is Associated with Disease Severity and Progression, but not NOD2/CARD15 Genotype
Ian DR Arnott MD1, Carol J Landers PhD1, Elaine J Nimmo PhD1, Hazel E Drummond BSc1, Ben KR Smith BSc1, Stephan R Targan MD1 and Jack Satsangi MD1
1Gastrointestinal Unit, University of Edinburgh Department of Medical Sciences, School of Clinical and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom; Inflammatory Bowel Disease Research, Cedars-Sinai Medical Centre, Los Angeles, California
Correspondence: Ian DR Arnott, Gastrointestinal Unit, University of Edinburgh, Department of Medical Sciences, School of Clinical and Molecular Medicine, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
Received 29 June 2004; Revised 0000; Accepted 12 July 2004.
Abstract
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= 0.008), small bowel disease (p < 0.02), and the need for surgery (p < 0.001). There was no association of antibody status to NOD2/CARD15 genotype.
CONCLUSION:
Reactivity to microbial components is associated with severe CD characterized by small bowel involvement, frequent disease progression, longer disease duration, and greater need for intestinal surgery.
