Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs

Background: Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established. Objective: The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs. Methods: We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA. Results: The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed, There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects. Conclusion: The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.