Immune responses to killed influenza vaccine in patients with type 1 diabetes: altered responses associated with HLA-DR 3 and DR 4.

To assess the immunologic differences related to histocompatibility leukocyte antigen (HLA) haplotypes in patients with type 1 diabetes, trivalent killed influenza virus vaccine was given in the fall, when no influenza occurred, to 59 patients with diabetes (mean age 16 years) and 64 siblings without diabetes (mean age 36 years). All subjects had normal hemagglutination inhibition antibody responses at days 14 and 42 after vaccination, with no significant differences noted between patients with diabetes and those without diabetes. However, subjects with HLA haplotypes DR 3, DR 4, or both had lower antibody responses to influenza A/Chile and B/USSR at 14 days after vaccination (p less than 0.02) than DR x/x controls (who lacked 3 or 4). Lymphocyte transformation (LT) responses before and after vaccination were similar for patients with diabetes and those without diabetes. Of significance was that subjects with HLA haplotypes DR 3, DR 4, or both had 41.1% LT responders at 42 days after vaccination, compared with subjects with HLA-DR x/x (lacking 3 or 4) who had 22.6% responders (p less than 0.03), when influenza A/Chile was used as an antigen. Although not significant, influenza antigens A/Philippines and B/USSR each showed similar trends with increased postvaccine LT responses. The HLA associations were independent of sex, age, and the presence of diabetes. These studies suggest that HLA haplotypes DR 3 and DR 4, which were clearly linked to type 1 diabetes mellitus, were also associated with altered immune responsiveness to influenza viral proteins.