Identification of autoantigens in psoriatic plaques using expression cloning
Identification of autoantigens in psoriatic plaques using expression cloning
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DOI：
10.1111/j.0022-202x.2004.22709.x
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发表时间：
2004-07-01
影响因子：
6.5
通讯作者：
Kupper, TS
中科院分区：
文献类型：
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作者：
Jones, DA;Yawalkar, N;Kupper, TS
为了寻找银屑病斑块中的自身抗原，我们用银屑病血清样本筛选斑块表皮的cDNA文库。这种方法在识别肿瘤抗原方面非常成功，但尚未广泛应用于自身免疫性疾病。我们确定了11个自身抗原，包括三个突出的反应性和合理的疾病相关性。它们是角蛋白13（K13），异质核核糖核蛋白-A1（hnRNP-A1）和以前未表征的蛋白质FLJ 00294。这些血清抗体筛查分别在40%、38%和27%的银屑病患者中表现出反应性。大多数阳性样品与所有三种反应，我们发现这是由于它们之间的交叉反应。银屑病患者外周血T细胞的酶联免疫斑点试验（ELISPOT）分析证实，这些自身抗原也被T细胞识别。这表明，这是一个可行的方法来确定自身免疫靶组织中的自身抗原，并建议这些抗原值得进一步研究银屑病。此外，正常对照组的外周血对这些自身抗原的反应频率与患者基本相同，这表明银屑病患者可能不仅具有能够对某些自身抗原反应的免疫系统，而且还具有允许这种正常反应发展为异常炎症的皮肤免疫调节改变。
To search for autoantigens in psoriatic plaques, we screened cDNA libraries of plaque epidermis with psoriatic serum samples. This approach has been highly successful in identifying tumor antigens, but has not been widely applied to autoimmune disease. We identified 11 autoantigens including three with prominent reactivity and plausible disease relevance. These are keratin 13 (K13), heterogeneous nuclear ribonucleoprotein-A1 (hnRNP-A1), and a previously uncharacterized protein, FLJ00294. Serum antibody screening for these demonstrated reactivity in 40%, 38%, and 27% of psoriasis patients, respectively. Most positive samples reacted with all three, and we found that this was due to cross-reactivity among them. Enzyme-linked immunospot assay (ELISPOT) analysis of psoriatic peripheral blood T cells confirmed that these autoantigens are also recognized by T cells. This demonstrates that this is a feasible method to identify autoantigens in an autoimmune target tissue, and suggests that these antigens warrant further study in psoriasis. Furthermore, but peripheral blood of normal controls reacted to these autoantigens with essentially the same frequencies as patients, suggesting that psoriatics may have not only an immune system which is capable of reacting to certain autoantigens, but also to a skin immunoregulatory alteration which allows this normal reactivity to develop into abnormal inflammation.