After artificial immunization (immunotherapy) with ragweed antigens, specific immunoglobulin G (IgG) antibody (Ab) response to Ra5 was significantly associated with HLA-Dw2 (P less than 0.0001). From a total of 61 treated patients, all 22 Dw2+ subjects made good IgG Ab responses to Ra5 by year 2 of therapy (21 by year 1), even though 8 of them had no detectable IgG Ab and 9 had no detectable IgE Ab before therapy. The prevalence of IgG Ab response among 39 Dw2- subjects was markedly lower; only 11 (28%) responded well after 1-9 yr of therapy. Both by univariate and multivariate statistical analysis, Dw2 was also found to be strongly associated with the quantity of IgG Ab produced. In particular, both the strength and significance of the association between Dw2 and log[IgG Ab] response to Ra5 increased over a 3-yr period of ragweed therapy (P = 10(-9) by year 3). Multiple regression analysis also revealed a weak association with HLA-B13, which became apparent only after year 2 of therapy. Genetic hypotheses for these findings are discussed. In particular, the possibility of a second Ir gene, Ir-Ra5', separate from HLA-Dw2 and possibly located elsewhere in the genome, is considered.

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