P108 : KIR-HLA LIGAND GENOTYPIC INTERACTION AND SUSCEPTIBILITY TO INFLAMMATORY BOWEL DISEASE

Abstract

Aim To elucidate the contribution of the Killer Ig-like Receptors (KIR) and their Human Leukocyte Antigen (HLA) ligands to Crohn’s Disease (CD) and Ulcerative Colitis (UC), the clinical subtypes of inflammatory bowel disease (IBD), an immune-mediated disease of the digestive tract. Methods and Cohorts MALDI-TOF mass spectrometry was used to profile the presence/absence of 16 KIR loci. HLA loci were genotyped using reverse format SSO strip, Luminex rSSO and a Roche 454 NGS system developed in our laboratory for complete HLA class I and II genotyping. Protein sequence data corresponding to HLA allelic typing was used to determine KIR ligands: Bw4/6 and C1/C2 epitope groups were assigned using residues at positions 77–83 in HLA-B and -C. Case-control analysis of 1232 Caucasian IBD patients (461 with UC: 277 medically refractory (MR), 184 non-MR; 771 with CD) and 203 Caucasian controls was performed using the chi-square test to compare the distribution of KIR genes KIR2DL2, KIR2DL3 and KIR3DL1, KIR3DS1 and their respective HLA ligands,C1, C2 and Bw4, across various disease phenotypes, including CD, UC and MR-UC disease. Results The homozygous genotypic combination of KIR2DL3, KIR3DL1 (homozygous KIR A/A haplotype) and Bw6 (absence of Bw4) with both C1 and C2 ligands present was shown to be highly significantly protective against ulcerative colitis (OR = 0.29, p Conclusions These data reveal a central role for a specific combination of KIRs and HLA ligands (i.e., homozygous KIR A haplotype, absence of Bw4 and C1/C2 heterozygosity) in protecting against UC disease and underscore the importance of analyzing genotypes of KIR together with their HLA ligands in disease association studies.