Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Short Communication Int Arch Allergy Immunol 2011;154:353–355 DOI: 10.1159/000321829 Common Filaggrin Null Alleles Are Not Associated with Hymenoptera Venom Allergy in Europeans A. Aslam   a A. Lloyd-Lavery   a D.A. Warrell   b S. Misbah   c G.S. Ogg   a   a  MRC Human Immunology Unit, University of Oxford, Oxford NIHR Biomedical Research Centre, Weatherall Institute of Molecular Medicine, b  Nuffield Department of Clinical Medicine, University of Oxford, and c  Department of Clinical Immunology, John Radcliffe Hospital, Oxford, UK Introduction Null mutations in filaggrin are associated with atopic eczema (atopic dermatitis, AD) and with asthma when present with AD [1]. The two most common mutations in Europeans, R501X and 2282del4, confer susceptibility to AD with a reported OR of 3.52 from a recent meta-anal- ysis [1] and account for 11% of the susceptibility to AD [2]. However, the presence of heterozygous filaggrin null mu- tations carries a variable clinical phenotype from normal through to severe disease. Other modifying factors are therefore involved, which are likely to include the innate and adaptive immune responses [3–5]. The prevailing disease model is that filaggrin insufficiency results in barrier dysfunction of the skin, which predisposes to al- lergen penetration, sensitisation and cutaneous inflam- mation. This results in further barrier dysfunction [3, 6]. However, whilst this is a plausible model, most forms of barrier dysfunction do not lead to sensitisation to com- mon allergens. Thus, it remains possible that filaggrin itself is involved directly in Th1/Th2 polarization. We sought to test the hypothesis that sensitisation to an al- lergen delivered to the skin, independent of the stratum corneum, is not associated with common filaggrin null mutations. Key Words Hymenoptera allergy  Atopic dermatitis  Filaggrin  Gene Abstract The association of filaggrin mutations with atopic eczema (atopic dermatitis, AD) is well established and it is thought that filaggrin dysfunction impairs the skin’s barrier function allowing allergen penetration and subsequent cutaneous sensitisation and inflammation. However, as most forms of barrier dysfunction are not associated with allergic sensitisa- tion to common allergens, the possibility that filaggrin itself is involved in Th1/Th2 polarisation remains. We tested the hypothesis that allergen delivered to the skin independently of the stratum corneum is not associated with filaggrin mu- tations. Wasp stings bypass the stratum corneum and de- liver antigen to the dermis. We found that European indi- viduals with AD (n = 32) have an increased frequency of the 2 commonest filaggrin null mutations (R501X and 2282del4) compared to those with vespid allergy (n = 56) and healthy controls (n = 30). Thus, filaggrin does not appear to have a downstream effect on the development of allergic disease, and it is indeed filaggrin’s role in the epithelial function that is likely to determine the link between filaggrin mutations and allergic sensitisation. Copyright © 2010 S. Karger AG, Basel Received: December 10, 2009 Accepted after revision: May 12, 2010 Published online: October 26, 2010 Correspondence to: Dr. Aamir Aslam Weatherall Institute of Molecular Medicine University of Oxford, John Radcliffe Hospital Oxford OX3 9DS (UK) Tel. +44 1865 222 443, Fax +44 1865 222 737, E-Mail aamir.aslam  @  imm.ox.ac.uk © 2010 S. Karger AG, Basel Accessible online at: www.karger.com/iaa