Major histocompatibility complex haplotypes in Spanish immunoglobulin A deficiency patients: a comparative fine...

The most consistent finding in Immunoglobulin A deficiency (IgAD) genetics is the presence of susceptibility factors located in the major histocompatibility complex (MHC). We have described the existence of at least two distinct susceptibility genes in the MHC present in different haplotypes. The aim of the present study was to locate with precision the susceptibility genes present in DR1- and DR7-positive haplotypes, taking advantage of their structural diversity, as opposed to the conserved nature of the DR3-extended susceptibility haplotype (DR3/B8), that hampers a more exhaustive scrutiny. A detailed analysis with 20 markers along the MHC in the 400 haplotypes present in 100 IgAD families, with special density at Class II locations, was performed to define the minimal shared susceptibility region present in all haplotypes carrying DR1 and, on the other hand, in all DR7-positive haplotypes. A comparison of the fine microsatellite allele structure of DR-extended haplotypes in the Spanish population with those described for Swedish and British families revealed no difference in DRB1*0101 and DRB1*0102 haplotypes between both populations. Our data suggest that the etiologic mutation present in DRB1*0101 and DRB1*0102 in North Europe (Sweden and UK) is missing in the Spanish DRB1*0101 haplotypes but is present in the DQB1/DRB1 region in DRB1*0102 haplotypes. The results obtained also indicated that the most likely susceptibility gene in the DR7 haplotypes is either DQA1 or DRB1.