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HLA haplotype segregation in families with allergic asthma.

In order to evaluate genetic linkage between Allergic Asthma (AA) and the HLA system, we studied 20 families having AA affected sib pairs and 8 families with Intrinsic Asthma (IA) affected sib pairs. All AA patients had a strong IgE immune response to the mite D. farinae. Serological HLA typing (A, B, C, DR, and DQ antigens) was performed by the standard microcytotoxicity assay. Genetic analysis was made by means of the "Affected sib pairs" method. Out of the 20 affected sib pairs, 14 shared two HLA haplotypes, five shared one HLA haplotype and one was HLA-non-identical. These results differed significantly from the random ratio 1:2:1 for sharing, 2, 1 or 0 haplotypes (p less than 0.0001), and was very close to that expected for a recessive mode of inheritance. In contrast, among the IA sib pairs there was not an important distortion in the pattern of haplotypes segregation. However, a significant association between any of the HLA alleles and the two types of Asthma studied was not found. The results suggest the existence of an HLA-linked recessive gene controlling the IgE immune responsiveness to mite allergens and conferring susceptibility to AA.