Divison of Dermatology and Venerology, Geneva University Hospitals, Geneva, Switzerland.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
Clin Rev Allergy Immunol. 2018 Dec;55(3):295-311. doi: 10.1007/s12016-017-8634-3.
In times of targeted therapies, innovative therapeutics become tools to further unravel the pathogenesis of the treated disease, thus influencing current pathogenetic concepts. Based on such paradigm shifts, the next generation of novel therapeutic targets might be identified. Psoriasis is a good example for the resulting most fruitful dialog between clinical and fundamental research. As a result of this, the key role of Th17 lymphocytes, some of their effector molecules, as well as mediators contributing to their maturation have been identified, many of these being targeted by some of the most effective drugs currently available to treat psoriasis. During this process, it became obvious that major parts of the puzzle remain yet to be uncovered or understood in much more detail. This review will therefore address the search for additional important effector cells other than Th17 lymphocytes, such as neutrophils, monocytes, and mast cells, mediators other than IL-17A, including some other IL-17 isoforms, and trigger factors such as potential autoantigens. This will lead to discussing the next generation of targeted therapies for psoriasis as well as treatment goals. These goals need to comprise both psoriasis as well as its comorbidities, as a comprehensive approach to manage the whole patient with all his health issues is urgently needed. Finally, given the substantial differences in resources available in different parts of the world, the global burden of psoriasis and options on how to care for patients outside developed countries will be assessed.
在靶向治疗时代,创新疗法成为进一步揭示治疗疾病发病机制的工具,从而影响当前的发病概念。基于这种范式转变,可以确定下一代新的治疗靶点。银屑病就是临床和基础研究之间产生最富有成效对话的一个很好的例子。因此,Th17 淋巴细胞、它们的一些效应分子以及有助于其成熟的介质的关键作用已被确定,其中许多已成为目前治疗银屑病最有效的药物的靶点。在这个过程中,很明显,仍然有很大一部分谜题有待进一步揭示或更详细地了解。因此,这篇综述将探讨寻找除 Th17 淋巴细胞以外的其他重要效应细胞,如中性粒细胞、单核细胞和肥大细胞,除了 IL-17A 以外的其他介质,包括其他一些 IL-17 同工型,以及潜在的自身抗原等触发因素。这将导致讨论银屑病的下一代靶向治疗以及治疗目标。这些目标需要包括银屑病及其合并症,因为迫切需要一种全面的方法来管理所有患者的所有健康问题。最后,鉴于世界不同地区的资源存在巨大差异,将评估银屑病的全球负担以及如何为发展中国家以外的患者提供护理的选择。