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结核性葡萄膜炎中的免疫反应及其治疗意义:从抗结核治疗到宿主导向疗法。

The immune response in tubercular uveitis and its implications for treatment: From anti-tubercular treatment to host-directed therapies.

作者信息

Putera Ikhwanuliman, Schrijver Benjamin, Ten Berge Josianne C E M, Gupta Vishali, La Distia Nora Rina, Agrawal Rupesh, van Hagen P Martin, Rombach Saskia M, Dik Willem A

机构信息

Department of Ophthalmology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Internal Medicine, Section Allergy and Clinical Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands; Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Ophthalmology, Faculty of Medicine, Universitas Indonesia, Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

Laboratory Medical Immunology, Department of Immunology, Erasmus University Medical Center, Rotterdam, the Netherlands.

出版信息

Prog Retin Eye Res. 2023 Jul;95:101189. doi: 10.1016/j.preteyeres.2023.101189. Epub 2023 May 25.

Abstract

Tubercular uveitis (TB-uveitis) remains a conundrum in the uveitis field, which is mainly related to the diverse clinical phenotypes of TB-uveitis. Moreover, it remains difficult to differentiate whether Mycobacterium tuberculosis (Mtb) is present in the ocular tissues, elicits a heightened immune response without Mtb invasion in ocular tissues, or even induces an anti-retinal autoimmune response. Gaps in the immuno-pathological knowledge of TB-uveitis likely delay timely diagnosis and appropriate management. In the last decade, the immunopathophysiology of TB-uveitis and its clinical management, including experts' consensus to treat or not to treat certain conditions with anti-tubercular treatment (ATT), have been extensively investigated. In the meantime, research on TB treatment, in general, is shifting more toward host-directed therapies (HDT). Given the complexities of the host-Mtb interaction, enhancement of the host immune response is expected to boost the effectiveness of ATT and help overcome the rising burden of drug-resistant Mtb strains in the population. This review will summarize the current knowledge on the immunopathophysiology of TB-uveitis and recent advances in treatment modalities and outcomes of TB-uveitis, capturing results gathered from high- and low-burden TB countries with ATT as the mainstay of treatment. Moreover, we outline the recent progress of HDT development in the pulmonary TB field and discuss the possibility of its applicability to TB-uveitis. The concept of HDT might help direct future development of efficacious therapy for TB-uveitis, although more in-depth research on the immunoregulation of this disease is still necessary.

摘要

结核性葡萄膜炎(TB-葡萄膜炎)在葡萄膜炎领域仍然是一个难题,这主要与TB-葡萄膜炎多样的临床表型有关。此外,目前仍难以区分结核分枝杆菌(Mtb)是否存在于眼组织中,是在没有Mtb侵入眼组织的情况下引发了增强的免疫反应,还是甚至诱导了抗视网膜自身免疫反应。TB-葡萄膜炎免疫病理知识的空白可能会延迟及时诊断和恰当治疗。在过去十年中,TB-葡萄膜炎的免疫病理生理学及其临床管理,包括专家对于是否用抗结核治疗(ATT)来治疗某些情况的共识,都得到了广泛研究。与此同时,总体而言,结核病治疗的研究正更多地转向宿主导向疗法(HDT)。鉴于宿主与Mtb相互作用的复杂性,增强宿主免疫反应有望提高ATT的疗效,并有助于克服人群中耐药Mtb菌株不断增加的负担。本综述将总结目前关于TB-葡萄膜炎免疫病理生理学的知识以及TB-葡萄膜炎治疗方式和结果的最新进展,涵盖以ATT为主要治疗方法的高负担和低负担结核病国家收集的结果。此外,我们概述了肺结核领域HDT发展的最新进展,并讨论其应用于TB-葡萄膜炎的可能性。HDT的概念可能有助于指导TB-葡萄膜炎有效治疗的未来发展,尽管仍有必要对该疾病的免疫调节进行更深入的研究。

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