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PFE M2 DEFI

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

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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 DR 1 - and DR 7 -positive haplotypes , taking advantage of their structural diversity , as opposed to the conserved nature of the DR 3 -extended susceptibility haplotype (DR 3 /B 8 ), 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 DR 1 and , on the other hand , in all DR 7 -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 DRB 1 *0101 and DRB 1 *0102 haplotypes between both populations . Our data suggest that the etiologic mutation present in DRB 1 *0101 and DRB 1 *0102 in North Europe (Sweden and UK ) is missing in the Spanish DRB 1 *0101 haplotypes but is present in the DQB 1 /DRB 1 region in DRB 1 *0102 haplotypes . The results obtained also indicated that the most likely susceptibility gene in the DR 7 haplotypes is either DQA 1 or DRB 1 .