137-P: HLA GENOTYPES IN PATIENTS REFERRED FOR CELIAC DISEASE TESTING: A REFERENCE LABORATORY EXPERIENCE

Abstract

Celiac disease is mediated by T lymphocytes in patients with genetic susceptibility. This genetic association is with certain HLA DQA1 and DQB1 genes. Most (90%-95%) patients with celiac disease have the DQ2 allele (encoded by DQA1∗05 and DQB1∗02), while the remainder have DQ8 (encoded by DQA1∗03:XX and DQB1∗03:02). Clinical significance of patients with only one copy of DQ2 allele encoded by DQB1∗02 and DQA1∗02 is not clear. Our laboratory performs nearly 12000 tests for celiac disease association annually. We present our interpretation schema and summary of the HLA DQ genotypes observed. Patient samples are typed for DQB1 and DQA1 genes by SSO and/or SSP method. Permissive gene pairs are ( Table 1 ). Patient that is heterozygous for DQ2 encoded by DQA1∗02:XX-DQB1∗02:02 (DQ2.2) without presence of DQA1∗05:XX in trans position is considered equivocal. [ Table 1 ] A total of 12652 samples were tested of which 5900 (47%) were permissive, 1328 (10%) equivocal and 5424 (43%) non permissive. Breakdown of the permissive gene pairs are (Table 2). 94% of the equivocal samples were heterozygous for DQ2.2, while most others had DQB1∗02:01 in combination with a non DQA1∗05 haplotype. [ Table 2 ] Majority of the permissive gene pairs where heterozygous for DQ2.5 or DQ8. Heterozygous DQ2.2 will be typed as DQ2 by serological methods but is considered equivocal for celiac disease assocaition. Thus, molecular methods that include typing for DQA1 and DQB1 are required for correct interpretation of permissive gene pairs for celiac disease.