STAT1 and STAT3 gain of function: clinically heterogenous immune regulatory disorders.

IF 3 4区 医学 Q2 ALLERGY
Peter Olbrich, Alexandra F Freeman
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引用次数: 0

Abstract

Purpose of review: The identification of STAT1 gain-of-function (GOF) in 2011 and STAT3 GOF in 2014 has advanced our understanding of the host immunity along the JAK/STAT pathway and allowed targeted treatment approaches. We review the clinical features and pathogenesis of STAT1 and STAT3 GOF and how this has shaped new approaches to therapy.

Recent findings: STAT1 GOF, initially described in patients with chronic mucocutaneous candidiasis (CMC) and autoimmune thyroid disease, is now recognized to cause early-onset multisystem autoimmunity and a range of infections. STAT3 GOF comprises mostly lymphoproliferation and autoimmunity but also with varying severity, including some with life threatening organ dysfunction. Treatment has evolved along with the understanding of the pathogenesis, with patients now receiving JAK inhibition to block upstream of the STAT defect with good response in autoimmunity and CMC in STAT1 GOF. Blockade of IL-6 signaling has also been used in STAT3 GOF. Hematopoietic cell transplantation had initial poor outcomes, but outcomes are now improving with focus on the control of inflammation pretransplant.

Summary: Understanding the pathogenesis of STAT1 and STAT3 GOF has allowed great recent advancements in therapy, but many questions remain as to the best approach to therapy for each patient's clinical presentation as well as the durability of these therapies.

STAT1 和 STAT3 功能增益:临床上的异源性免疫调节紊乱。
综述的目的:2011年发现的STAT1功能增益(GOF)和2014年发现的STAT3功能增益(GOF)加深了我们对JAK/STAT通路上宿主免疫的理解,并使我们能够采用靶向治疗方法。我们回顾了STAT1和STAT3 GOF的临床特征和发病机制,以及这如何塑造了新的治疗方法:STAT1 GOF最初是在慢性皮肤粘膜念珠菌病(CMC)和自身免疫性甲状腺疾病患者身上发现的,现在已被确认可导致早发性多系统自身免疫病和一系列感染。STAT3 GOF 主要包括淋巴细胞增殖和自身免疫,但也有不同的严重程度,包括一些危及生命的器官功能障碍。随着对发病机制的认识不断深入,治疗方法也在不断发展,现在患者可以接受JAK抑制剂来阻断STAT缺陷的上游,对自身免疫和STAT1 GOF的CMC反应良好。阻断 IL-6 信号也被用于 STAT3 GOF。摘要:对STAT1和STAT3 GOF发病机制的了解使最近的治疗取得了巨大进步,但针对每位患者临床表现的最佳治疗方法以及这些疗法的持久性仍存在许多问题。
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来源期刊
CiteScore
5.90
自引率
3.60%
发文量
109
审稿时长
6-12 weeks
期刊介绍: This reader-friendly, bimonthly resource provides a powerful, broad-based perspective on the most important advances from throughout the world literature. Featuring renowned guest editors and focusing exclusively on one to three topics, every issue of Current Opinion in Allergy and Clinical Immunology delivers unvarnished, expert assessments of developments from the previous year. Insightful editorials and on-the-mark invited reviews cover key subjects such as upper airway disease; mechanisms of allergy and adult asthma; paediatric asthma and development of atopy; food and drug allergies; and immunotherapy.
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