HLA-DQ and celiac disease: a novel risk gradient for predisposed subjects

BACKGROUND. Celiac disease (CeD) is an immune-mediated systemic disorder elicited by gliadin, a prolamine found in wheat and related proteins, occurring in genetically predisposed individuals, carrying HLA-DQ2 and/or DQ8. Several heterodimers have been associated with CeD: the HLA-DQ2.5, occurring in approximately 90% of CeD patients, is encoded by the DQB1*02 and DQA1*05 alleles both in cis and in trans; the HLA-DQ2.2 heterodimer, encoded by the DQB1*02 and DQA1*02 allele; and the HLA- DQ8 heterodimer, encoded by the DQB1*03:02 and DQA1*03 alleles. AIMS. We aimed: 1) To characterize HLA polymorphisms; 2) to confirm the association between HLA class II genes with CeD; 3) to assess their role in CeD genetic susceptibility by re-defining the current risk pyramid of genetically predisposed individuals. METHODS. We included celiac children diagnosed based on European Society for Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) criteria and controls. The control group included healthy Italian individuals and affected family-based controls (AF-BAC). All individuals were typed for DRB1, DQA1, and DQB1 genes by sequence-specific primer–polymerase chain reaction (SSP-PCR). Disease risks are expressed as 1:N, where N is the number of individuals among which one patient is present. Considering a disease prevalence of 1:100 in the general population, for each HLA-DQ category, N is calculated as a percentage of controls with that particular HLA-DQ status multiplied by 100 and divided by percentage of patients with the same DQ typing. RESULTS: We included 778 CeD patients (M:277= F:511), and 551 controls (292 healthy Italian individuals and 259 affected family-based controls). In conclusion, the new risk pyramid shows an increased risk for all haplotypes; it is reasonable to assert that there is an increased CeD risk in presence of DQ*B102 either as a single copy or combination with other alleles.