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Expression1
* Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, Imperial College, National Heart and Lung Institute, London, United Kingdom; and
Unit of Pneumology, University of Louvain, Brussels, Belgium
Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-
-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF- expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (
8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (2-fold increase, p = 0.02) and in nasal TGF- mRNA (p = 0.05) were also observed, and TGF- mRNA correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF- expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 C.P. was supported by a fellowship from the European Respiratory Society (LTRF-2002-037) and from the Fonds National de la Recherche Scientifique, Belgium (FRSM 3.4.565.06). K.T.N.-A. was supported by a grant from GlaxoSmithKline/Imperial College Trust as part of its Advanced Drug Discovery Initiative.
2 C.P. and K.T.N.-A. contributed equally to the present study.
3 Address correspondence and reprint requests to Prof. S. R. Durham, Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, U.K. E-mail address: s.durham{at}imperial.ac.uk
4 Abbreviations used in this paper: IT, immunotherapy; a.u. arbitrary unit; J chain, joining chain; m-IgA, monomeric IgA; Phl p, Phleum pratense; p-IgA, polymeric IgA; S-IgA, secretory IgA.
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