HLA-DRB1 Alleles May Influence Disease Phenotype in Patients With Inflammatory Bowel Disease: A Critical Reappraisal With Review of the Literature

PURPOSE The HLA region has been implicated in determining the disease susceptibility or the clinical phenotype of inflammatory bowel disease. The aim of this study was to assess the relation between HLA-DRB1 alleles with the clinical features of Crohns disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies.METHODS Blood samples were obtained from 102 Crohns disease patients, 114 ulcerative colitis patients, and 264 unrelated healthy controls. Anti-neutrophil cytoplasmics were detected by a standard immunofluorescence method, and anti-Saccharomyces cerevisiaes were examined by an enzyme-linked immunosorbent assay immunoglobulin G/immunoglobulin A commercial assay. HLA-DRB1 typing of 26 alleles was performed by polymerase chain reaction sequence-specific primes. Patients were phenotyped according to gender, disease location, extent, and behavior, surgical resection, need of steroid, and anti-neutrophil cytoplasmic/anti-Saccharomyces cerevisiae status.RESULTS As a whole, after applying Bonferronis correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohns disease or ulcerative colitis was found. After stratifying HLA-DRB1 alleles by clinical phenotypes of patients with ulcerative colitis, an excess of DRB1*1309*1320*1325*1329 allele (DR13) was found in conjunction with pancolitis (P < 0.0001), surgical resection (P < 0.0003), and extraintestinal manifestations (P < 0.0001). In Crohns disease patients, an excess of DRB1*0304*0305*0307*0309 allele (DR3) was found in those with colonic disease (P < 0.0001) and patients with extraintestinal manifestations (P = 0.0003). This statistical association, however, emerged in only 3 of 114 patients with ulcerative colitis and in 3 of 102 patients with Crohns disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic.CONCLUSIONS Some clinical features of Crohns disease and ulcerative colitis may be influenced by specific HLA-DR alleles; in particular, in ulcerative colitis some alleles appear to segregate with more aggressive disease, whereas in Crohns disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.Presented in part at the Digestive Disease Week, New Orleans, May 19 to 24, 1998, New Orleans, Louisiana.This work has been supported by a grant of the Health Minister (No. GARC0102).