Delayed hypersensitivity to aminopenicillins is related to major histocompatibility complex genes

Background: Although in some cases delayed hypersensitivity may be observed, beta-lactam antibiotics frequently induce immediate allergic IgE- mediated reactions with the specificity localized in the acyl-side chain structure. Generally, delayed immunologic reactions are related to sensitized T lymphocytes and major histocompatibility complex restricted. Objective: To investigate the prevalence of HLA class I and II antigens in patients with delayed hypersensitivity to aminopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. Methods: We assessed 24 patients with history of delayed hypersensitivity to aminopenicillins using (1) skin test with penicilloyl polylysine, minor determinant mixture, benzylpenicillin, amoxicillin, and ampicillin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicillin; (3) RAST for penicilloyls G and V; and (4) oral challenges with amoxicillin, ampicillin, and penicillin V in 18/24 patients. All patients were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by χ² test 2 x 2 contigency tables, according to Svejgaard, were used for comparison between patients and random Italian population (522 subjects). Results: In the patients group we found higher prevalence of HLA A2 (12/24 = 50%, RR = 6.76 P <.001, EF = 0.425), DRw52 (20/24 = 83.3%, RR = 9.28, P <.001, EF = 0.74), and lower frequency of DR4 (3/24 = 12% ns). Conclusions: These data suggest that the immune mechanisms involved in adverse reactions to aminopenicillins in vivo are related to genetic markers of immune response and confirms that the presentation of penicillin-hapten determinants to lymphocyte is major histocompatibility complex restricted.