title: HLA-DRB1 alleles may influence disease phenotype in patients with inflammatory bowel disease: a critical reappraisal with review of the literature.
abstract: OBJECTIVE
  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 Crohn's disease and ulcerative colitis and the presence of anti-neutrophil cytoplasmic and anti-Saccharomyces cerevisiae antibodies.
  
  
  METHODS
  Blood samples were obtained from 102 Crohn's 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 Bonferroni's correction for multiple comparisons, no significant association of HLA-DRB1 alleles with Crohn's 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 Crohn's 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 Crohn's disease. We found no association with the presence of anti-Saccharomyces cerevisiae or anti-neutrophil cytoplasmic.
  
  
  CONCLUSIONS
  Some clinical features of Crohn's 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 Crohn's disease different alleles cosegregate in patients with colonic disease and extraintestinal manifestations.
authors.affiliation: Department of Internal Medicine, Unit of Gastroenterology and Endoscopy, Casa Sollievo della Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Annese
authors.forename: A
authors.initials: A
authors.lastname: Piepoli
authors.forename: A
authors.initials: A
authors.lastname: Latiano
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
authors.forename: G
authors.initials: G
authors.lastname: Napolitano
authors.forename: N
authors.initials: N
authors.lastname: Caruso
authors.forename: E
authors.initials: E
authors.lastname: Cocchiara
authors.forename: L
authors.initials: L
authors.lastname: Accadia
authors.forename: F
authors.initials: F
authors.lastname: Perri
authors.forename: A
authors.initials: A
authors.lastname: Andriulli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000908:Antibodies, Fungal; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012189:Retrospective Studies; D012441:Saccharomyces cerevisiae / Q000276:immunology
chemical_list: D000908:Antibodies, Fungal; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains