HLA-DPB1 ALLELES PROVIDE PROTECTION AGAINST CROHNS-DISEASE IN CAUCASIANS

Objective: The aim of this study was to identify immunogenetic markers of susceptibility or protection in Crohn's disease. Design: HLA class II antigen frequencies were analysed and compared in a group of 118 S wedish patients with Crohn's disease and 158 unrelated healthy control s. Methods: HLA class II loci DRB1, DQB1 and DPB1 were typed using seq uence-specific oligonucleotide probes to analyse enzymatically amplifi ed locus-specific DNA. Results: HLA DR specificities, DQB1 alleles and DR/DQ haplotypes were not significantly associated with Crohn's disea se. In contrast, significant differences were detected for HLA DPB104 01, which was reduced in patients with Crohn's disease (39.5%) compare d with healthy controls (65.8%), giving rise to a relative risk of 0.3 (P<0.001). Furthermore, following analysis of relative predisposition al effects, additional protective effects were observed for DPB10201 and DPB10801. Overall, 47.8% of the patients compared with 81.3% of t he controls had at least one of the alleles negatively associated with Crohn's disease (relative risk 0.2, chi2=31.8, P<0.001). Despite the negative association with DPB1 alleles, neither HLA DR specificities n or DQ alleles had any impact on disease susceptibility. Conclusion: HL A DPB1 alleles exhibit a negative association with Crohn's disease and , therefore, may be of importance for protection against the developme nt of this disease.