Patients with co-existing psoriasis and eczema: key to understand the pathogenesis of chronic inflammatory skin diseases

牛皮癣和湿疹共存的患者：了解慢性炎症性皮肤病发病机制的关键

• 批准号: 282660335
• 负责人: Professor Dr. Kilian Eyerich, Ph.D.
• 金额: --
• 依托单位: Klinik für Dermatologie und Venerologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/282660335?language=en
• 关键词: Patients; co; existing; psoriasis; eczema

Chronic inflammatory skin diseases such as psoriasis or eczema challenge modern medicine, as they are frequent, mean a devastating life quality for affected patients and come with a high socio-economic burden. Those complex diseases are based on individual predisposition, modulating environmental factors, and altered immune responses. While a lot of progress was made elucidating the pathogenesis of chronic inflammatory skin diseases, basic questions remain unanswered: "what are primary triggers of the disease?" or "What leads to chronic course of the disease?". A reason for those unresolved riddles is the heterogeneity of both psoriasis and eczema. To achieve a substantial progress, a model is needed that enables to distinguish the individual genetic code from molecular expression changes in lesional skin. Such a model is the basis of this application: patients with co-existing psoriasis and eczema.This interdisciplinary approach will compare molecular events in lesional skin in patients affected by both psoriasis and eczema at the same time. In these patients, it is possible to observe expression changes of different diseases at the same genetic background. This is important, as so far only expression changes can be modulated therapeutically. Factors that are regulated specifically in one inflammatory skin condition represent highly promising diagnostic and therapeutic targets. In pilot studies, we identified NOS2 and CCL27 as specifically and highly regulated markers in psoriasis or eczema, respectively. Here, we will validate and functionally characterize those two markers. Furthermore, systematic computational biology approaches will identify further candidate targets.

牛皮癣或湿疹等慢性炎症性皮肤病对现代医学提出了挑战，因为它们很常见，对受影响的患者意味着毁灭性的生活质量，并伴随着沉重的社会经济负担。这些复杂的疾病是基于个体的易感性、调节环境因素和改变的免疫反应。虽然在阐明慢性炎症性皮肤病的发病机制方面取得了很大进展，但基本的问题仍然没有得到回答：“这种疾病的主要诱因是什么？”或者“是什么导致了慢性病程？”这些未解之谜的一个原因是牛皮癣和湿疹的异质性。为了取得实质性的进展，需要一种模型来区分皮损皮肤中的个体遗传密码和分子表达变化。这样的模型是这项应用的基础：牛皮癣和湿疹共存的患者。这种跨学科的方法将比较同时受到牛皮癣和湿疹影响的患者皮损皮肤中的分子事件。在这些患者中，可以在相同的遗传背景下观察不同疾病的表达变化。这一点很重要，因为到目前为止，只有表达变化可以通过治疗来调节。在一种炎症性皮肤状况下特定调节的因子代表着非常有希望的诊断和治疗靶点。在初步研究中，我们确定NOS2和CCL27分别是银屑病或湿疹的特异性和高度调控的标志物。在这里，我们将验证并从功能上描述这两个标记。此外，系统的计算生物学方法将确定更多的候选目标。

项目成果

Is the humoral immunity dispensable for the pathogenesis of psoriasis?

• DOI: 10.1111/jdv.15101
• 发表时间: 2019-01-01
• 期刊: JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
• 影响因子: 9.2
• 作者: Thomas, J.;Kuepper, M.;Garzorz-Stark, N.
• 通讯作者: Garzorz-Stark, N.

A novel molecular disease classifier for psoriasis and eczema

• DOI: 10.1111/exd.13077
• 发表时间: 2016-10-01
• 期刊: EXPERIMENTAL DERMATOLOGY
• 影响因子: 3.6
• 作者: Garzorz-Stark, Natalie;Krause, Linda;Eyerich, Kilian
• 通讯作者: Eyerich, Kilian

Identifying hidden drivers of heterogeneous inflammatory diseases

识别异质炎症性疾病的隐藏驱动因素

• DOI: 10.1101/2020.07.25.221309
• 发表时间: 2020
• 期刊: bioRxiv
• 作者: Batra R;Garzorz-Stark N;Lauffer F;Jargosch M;Pilz AC;Roenneberg S;Schäbitz A;Böhner A;Seiringer P;Thomas J;Fereydouni B;Kutkaite G;Menden M;Tsoi LC;Gudjonsson JE;Theis FJ;Biedermann T;Schmidt-Weber CB;Müller N;Eyerich S;Eyerich K
• 通讯作者: Eyerich K