Mittermann Irene, Reininger Renate, Zimmermann Maya, Gangl Katharina, Reisinger Jürgen, Aichberger Karl J, Greisenegger Elli K, Niederberger Verena, Seipelt Joachim, Bohle Barbara, Kopp Tamara, Akdis Cezmi A, Spitzauer Susanne, Valent Peter, Valenta Rudolf
Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Vienna, Austria.
J Invest Dermatol. 2008 Jun;128(6):1451-9. doi: 10.1038/sj.jid.5701195. Epub 2007 Dec 13.
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.
新生多肽相关复合物的α链Hom s 2是一种细胞内自身抗原，已在特应性皮炎患者的IgE自身抗体中被鉴定出来。我们研究了对纯化重组Hom s 2（rHom s 2）的体液免疫和细胞免疫反应。rHom s 2表现出与外源性过敏原相当的IgE反应性，但不会诱导相关的嗜碱性粒细胞脱颗粒。后者可能归因于这样一个事实，即通过用rHom s 2片段进行IgE表位作图显示，患者识别出Hom s 2上的单个表位。与外源性过敏原不同，rHom s 2具有内在能力，可在特应性和非特应性个体的培养外周血单个核细胞中诱导IFN-γ释放。来自Hom s 2刺激的外周血单个核细胞的含IFN-γ培养上清液会导致呼吸道上皮细胞层解体和皮肤角质形成细胞凋亡，而这可以用中和性抗IFN-γ抗体来抑制。我们的数据表明，Hom s 2自身抗原可导致IFN-γ介导的细胞损伤。
