Valenta R, Natter S, Seiberler S, Wichlas S, Maurer D, Hess M, Pavelka M, Grote M, Ferreira F, Szepfalusi Z, Valent P, Stingl G
Institute of General and Experimental Pathology, Vienna General Hospital, University of Vienna Medical School, Austria.
J Invest Dermatol. 1998 Dec;111(6):1178-83. doi: 10.1046/j.1523-1747.1998.00413.x.
Atopy is a genetically determined disorder that affects 10%-20% of the population. Many symptoms of patients with atopy (allergic rhinitis, conjunctivitis, asthma, and anaphylaxis) result from events occurring after crosslinking of cell-bound IgE by per se innocuous environmental antigens. The frequently raised hypothesis that autosensitization can also be a pathogenetic factor in atopy, gained support by our recent demonstration of IgE antibodies against human proteins in atopic dermatitis patients. To unravel the molecular nature of IgE-defined autoantigens, we used serum IgE from atopic dermatitis patients to screen a human epithelial cDNA expression library. One of the cDNA-encoding IgE-reactive products contained 1501 bp of a 2274 bp open-reading frame finally identified by sequence analysis of two additional cDNA clones resulting from oligonucleotide screening. The IgE-defined autoantigen, designated Hom s 1, exhibited an almost complete sequence identity with a recently described antigen recognized by cytotoxic T cells of a squamous cell carcinoma patient. Purified recombinant Hom s 1 specifically bound IgE from patients with severe atopy. When used as immunogen in rabbits, recombinant Hom s 1 gave rise to an anti-serum that reacted with a cytoplasmic protein exhibiting a broad cellular and tissue reactivity (skin, lung >> gastrointestinal tract >> muscle, brain) and identified a 55 kDa protein in blotted serum IgE preparations. The attractive possibility remains that the Hom s 1-triggered IgE response contributes to the events resulting in allergic tissue inflammation. If so, the respective recombinant molecule may serve as a paradigmatic tool for the diagnosis and treatment of patients with "intrinsic" atopy.
特应性是一种由遗传决定的疾病，影响着10%-20%的人群。特应性患者的许多症状（过敏性鼻炎、结膜炎、哮喘和过敏反应）是由本身无害的环境抗原与细胞结合的IgE交联后发生的事件引起的。自身致敏也可能是特应性发病机制中的一个因素这一假说，因我们最近在特应性皮炎患者中发现针对人类蛋白质的IgE抗体而得到支持。为了阐明IgE定义的自身抗原的分子性质，我们使用特应性皮炎患者的血清IgE筛选人上皮cDNA表达文库。其中一个编码IgE反应性产物的cDNA包含一个2274 bp开放阅读框中的1501 bp，通过对另外两个由寡核苷酸筛选得到的cDNA克隆进行序列分析最终确定。这个由IgE定义的自身抗原，命名为Hom s 1，与最近描述的一名鳞状细胞癌患者的细胞毒性T细胞识别的抗原几乎具有完全的序列同一性。纯化的重组Hom s 1特异性结合重症特应性患者的IgE。当用作兔的免疫原时，重组Hom s 1产生了一种抗血清，该抗血清与一种细胞质蛋白发生反应，这种蛋白具有广泛的细胞和组织反应性（皮肤、肺>>胃肠道>>肌肉、脑），并在印迹的血清IgE制剂中鉴定出一种55 kDa的蛋白。Hom s 1引发的IgE反应可能导致过敏性组织炎症这一诱人的可能性仍然存在。如果是这样，相应的重组分子可能成为诊断和治疗“内源性”特应性患者的范例工具。
