HLA-DQ2 HETERODIMER IN THE DIAGNOSIS OF CELIAC DISEASE

Objective: Genetic predisposition to CD is strongly associated with HLA-DQ alleles. The major- ity of patients carry HLA-DQ2 heterodimer (HLA-DQ(α1*0501,β1*02) heterodimer) encoded by DQA1*0501 and DQB1*02 genes, either in cis or trans. The remaining patients carry either DQ8 heterodimer (HLA-DQ (α1*0301,β1*0302) heterodimer) or part of the DQ2 heterodimer. The aim of the present study was to investigate these findings in Croatian CD patients. Methods: Sixty-three unrelated children diagnosed with CD and 119 unrelated healthy controls were typed for HLA-DQA1 and DQB1 alleles. HLA typing was performed by polymerase chain reaction-sequence specific oligo - nucleotide probes (PCR-SSOP) method. Results: The statistically highly significant (p<10 -5) difference between patients and controls was found for DQA1*0501 allele (64.3% in patients vs. 24.8% in controls; RR=5.5), for DQB1*02 allele (61.9% in patients vs 13.4% in controls; RR=10.5) and for DQA1*0501-DQB1*02 haplotype (51.6% in patients vs. 8.1% in controls; RR=12.9). The analysis for HLA-DQ heterodimers revealed the presence of HLA-DQ2 heterodimer in 59 (93.7%) patients and in 21 (17.6%) controls. In patients, an increase in homozygotes for DQ2 heterodimer (20.6% in pa- tients vs. 1.7% in controls, RR=15.2), as well as an increase in heterozygotes for DQ2 heterodimer in cis (61.9% in patients vs. 11.8% in controls; RR=12.2) was observed. Among 4 patients negative for DQ2 heterodimer, 3 were positive for DQ8 heterodimer, and 1 patient carried only DQB1*02 allele. Conclusion: The value of this typing in the diagnosis of CD lies in its ability to exclude disease in the case of a negative result for the presence of DQ2 heterodimer.