DELAYED-HYPERSENSITIVITY TO AMINOPENICILLINS IS RELATED TO MAJOR HISTOCOMPATIBILITY COMPLEX GENES

Background: Although in some cases delayed hypersensitivity may be obs erved, beta-lactam antibiotics frequently induce immediate allergic Ig E-mediated reactions with the specificity localized in the acyl-side c hain structure. Generally, delayed immunologic reactions are related t o sensitized T lymphocytes and major histocompatibility complex restri cted. Objective: To investigate the prevalence of HLA class I and II a ntigens in patients with delayed hypersensitivity to arainopenicillins in order to evaluate a relationship between major histocompatibility complex immune response genes and aminopenicillins hypersensitivity. M ethods: We assessed 24 patients with history of delayed hypersensitivi ty to aminopenicillins using (1) skin test with penicilloyl polylysine , minor determinant mixture, benzylpenicillin, amoxicillin, and ampici llin; (2) patch tests with benzylpenicillin, amoxicillin, and ampicill in; (3) RAST for penicilloyls G and V; and (4) oral challenges with am oxicillin, ampicillin, and penicillin V in 18/24 patients. All patient s were typed by microlymphotoxicity standard test for HLA class I and II antigens. Statistical analysis by chi(2) test 2 X 2 contigency tabl es, 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 d ata suggest that the immune mechanisms involved in adverse reactions t o aminopenicillins in vivo are related to genetic markers of immune re sponse and confirms that the presentation of penicillin-hapten determi nants to lymphocyte is major histocompatibility complex restricted.