Association of pyrazolone drug hypersensitivity with HLA-DQ and DR antigens

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Abstract
In sensitive patients pyrazolone drugs can precipitate adverse reactions ranging from urticaria and angioedema to anaphylactic shock, presumably by immunological, IgE-mediated mechanism. However, up to now no genetic factors influencing the development of allergic reaction have been reported in this type of hypersensitivity. The aim of our study was the investigation whether the susceptibility to development of pyrazolone drugs hypersensitivity (PDH) reactions was associated with HLA class II antigens. To test this hypothesis we studied the distribution of HLA-DR and DQ antigens in 26 pyrazolone sensitive patients and control groups including unselected general population and clearly defined atopic and non-atopic groups. Significantly higher frequencies of DQ 7 and DR11 antigens were found in PDH group as compared with control unselected population (RR= 16.48, P < 0.0001; Pcor < 0.002 and RR = 4.57, P = 0.0002; Pcor = 0.003 for DQ and DR antigen respectively). Similarly, statistically significant increased frequencies of DQ 7 and DR11 in patients with PDH were observed compared with atopic control group (RR = 18.43, P < 0.0001; Pcor < 0.002 and RR = 6.33, P = 0.0007; Pcor = 0.01, for DQ and DR antigen respectively). However, in comparison to non-atopic control group only the frequency of DQ 7 antigen was significantly increased (RR = 15.42, P = 0.0001; Pcor = 0.0015). DQ 7 antigen was present in 46.1% of PDH patients compared with 4.9%, 4.4% and 5.3% in the general population, atopic and non-atopic groups respectively, suggesting pyrazolone hypersensitivity as a trait positively correlated with this HLA antigen. Our data suggest a genetic predisposition to pyrazolone hypersensitivity reactions, linked to HLA-DQ locus.