The IgE-reactive autoantigen Hom s 2 induces damage of respiratory epithelial cells and keratinocytes via induction of IFN-gamma

IgE 反应性自身抗原 Hom s 2 通过诱导 IFN-γ 引起呼吸道上皮细胞和角质形成细胞损伤

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作者:Irene Mittermann, Renate Reininger, Maya Zimmermann, Katharina Gangl, Jürgen Reisinger, Karl J Aichberger, Elli K Greisenegger, Verena Niederberger, Joachim Seipelt, Barbara Bohle, Tamara Kopp, Cezmi A Akdis, Susanne Spitzauer, Peter Valent, Rudolf Valenta

Abstract

Hom s 2, the alpha-chain of the nascent polypeptide-associated complex, is an intracellular autoantigen that has been identified with IgE autoantibodies from atopic dermatitis patients. We investigated the humoral and cellular immune response to purified recombinant Hom s 2 (rHom s 2). rHom s 2 exhibited IgE reactivity comparable to exogenous allergens, but did not induce relevant basophil cell degranulation. The latter may be attributed to the fact that patients recognized single epitopes on Hom s 2 as revealed by IgE epitope mapping with rHom s 2 fragments. In contrast to exogenous allergens, rHom s 2 had the intrinsic ability to induce the release of IFN-gamma in cultured peripheral blood mononuclear cells from atopic as well as non-atopic individuals. IFN-gamma-containing culture supernatants from Hom s 2-stimulated peripheral blood mononuclear cells caused disintegration of respiratory epithelial cell layers and apoptosis of skin keratinocytes, which could be inhibited with a neutralizing anti-IFN-gamma antibody. Our data demonstrate that the Hom s 2 autoantigen can cause IFN-gamma-mediated cell damage.

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