1. ¹Inserm U-724, Faculté de Médecine, University of Nancy-Henri Poincaré and University Hospital Center (CHU) of Nancy, Nancy, France
2. ²Department of Internal Medicine and Geriatrics, UCSC-Allergy Unit, Complesso Integrato Columbus, Rome, Italy
3. ³IRCCS Oasi Maria SS, Troina, Italy

Correspondence: Dr J-L Guéant, Inserm U-724, University of Nancy-Henri Poincaré, BP 184, F- 54505, Nancy-Vandoeuvre, France. E-mail: jl.gueant@chu-nancy.fr

⁴These authors have contributed equally to this work.

Received 24 July 2006; Revised 18 March 2007; Accepted 18 March 2007; Published online 1 May 2007.

Abstract

Tumor necrosis factor- (TNF-) is released from mast cells via an immunoglobulin E (IgE)-dependent mechanism. The variant G>A at –308 of TNFA is part of an extended haplotype HLA-A1-B8-DR3-DQ2 and influences the gene expression. We evaluated this variant in relation to IgE-mediated reactions to betalactams, in 427 subjects, including 167 cases and 260 age- and gender-paired controls. TNFA GG genotype was a significant independent predictor of the primary risk of betalactam allergy, concurrently with total IgE level, with an age- and sex-adjusted odds ratio estimated at 2.45 (95% confidence interval: 1.18–5.08, P=0.0163). Cases with –308AA genotype had a higher serum level of specific IgE than those with –308GA/GG genotype, with median levels (relative units) of 4.6 (inter-quartiles: 3.9–10.6) and 2.2 (1.4–4.3), respectively (P=0.0046). In conclusion, our results suggest an ambivalent influence of a genetic determinant of pro-inflammatory pathways on IgE-mediated hypersensitivity to betalactams.