DIFFERENT DOSE-EFFECT OF HLA-DQ-ALPHA-BETA HETERODIMERS IN INSULIN-DEPENDENT DIABETES-MELLITUS AND CELIAC-DISEASE SUSCEPTIBILITY

To compare the quantitative effect of the DQalphabeta heterodimers DQalpha52Arg+, beta57Asp- and DQalpha1*0501,beta1*0201 on susceptibility to IDDM and CD, we characterized, at the genomic level, the DQalpha 52 and DQbeta 57 residues of 50 IDDM Italian patients observed in Rome. The results were compared with those of a previous study concerning the oligotyping of DQ dimers in a group of CD children belonging to the same population. Our data confirm that both diseases are primarily associated with HLA-DQalphabeta heterodimers, but the distributions of the respective susceptible DQA1 and DQB1 alleles in the two diseases were different. In fact, the highest risk of IDDM is for subjects alphaSS,betaSS that could express, by either cis- or trans-association, four susceptible heterodimers and decreases in proportion to the number of these; in regard to CD, the highest risk was found for individuals who carried only one predisposing heterodimer.