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银屑病与新型生物制剂:阻断T-AP之舞

Psoriasis and the new biologic agents: interrupting a T-AP dance.

作者信息

Walsh Scott R A, Shear Neil H

机构信息

Department of Medicine, Division of Dermatology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, Toronto, Ont.

出版信息

CMAJ. 2004 Jun 22;170(13):1933-41. doi: 10.1503/cmaj.1031335.

Abstract

Psoriasis is an immune-mediated skin disease in which chronic T-cell stimulation by antigen-presenting cells (APC) occurs in the skin. This interplay between the T-cell and APC has been likened to a "T-AP dance" where specific steps must occur in sequence to result in T-cell activation and the disease phenotype; otherwise T-cell anergy would occur. Several novel engineered proteins designed to block specific steps in immune activation (biologic agents) have demonstrated efficacy in the treatment of psoriasis. These agents include fusion proteins, monoclonal antibodies and recombinant cytokines. These medications act at specific steps during the T-AP dance either to inhibit T-cell activation, costimulation and subsequent proliferation of T-cells, lead to immune deviation or induce specific cytokine blockades. The potential increased selectivity for specific pathways in immune activation, clinical efficacy and relative safety of these new agents offers an alternative for the treatment of moderate to severe psoriasis.

摘要

银屑病是一种免疫介导的皮肤病,其中抗原呈递细胞(APC)在皮肤中对T细胞进行慢性刺激。T细胞与APC之间的这种相互作用被比作一场“T-AP舞蹈”,其中特定步骤必须按顺序发生才能导致T细胞活化和疾病表型;否则会发生T细胞无反应性。几种旨在阻断免疫激活特定步骤的新型工程蛋白(生物制剂)已在银屑病治疗中显示出疗效。这些制剂包括融合蛋白、单克隆抗体和重组细胞因子。这些药物在T-AP舞蹈的特定步骤起作用,要么抑制T细胞活化、共刺激和随后的T细胞增殖,导致免疫偏离,要么诱导特定细胞因子阻断。这些新药对免疫激活特定途径潜在的更高选择性、临床疗效和相对安全性为中重度银屑病的治疗提供了一种替代方案。

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