血浆基质金属蛋白酶升高与结核分枝杆菌血流感染和人类免疫缺陷病毒相关结核病的死亡率有关。

IF 5 2区医学 Q2 IMMUNOLOGY

Journal of Infectious Diseases Pub Date : 2024-09-02 DOI:10.1093/infdis/jiae296

Naomi F Walker, Charlotte Schutz, Amy Ward, David Barr, Charles Opondo, Muki Shey, Paul T Elkington, Katalin A Wilkinson, Robert J Wilkinson, Graeme Meintjes

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引用次数: 0

摘要

人类免疫缺陷病毒（HIV）相关结核病（TB）的死亡率很高，尤其是在住院患者中。在 433 名因肺结核症状住院的 HIV 感染者中，我们研究了血浆基质金属蛋白酶（MMP）和基质衍生生物标志物与肺结核诊断、死亡率和结核分枝杆菌（Mtb）血流感染（BSI）的关系。与其他诊断相比，MMP-8 在确诊肺结核和 Mtb-BSI 中升高，与细胞外基质分解产物呈正相关。基线 MMP-3、-7、-8、-10 和 PIIINP 与 Mtb-BSI 和 12 周死亡率相关。这些发现表明，MMP失调与晚期HIV-结核病的病理生理学有关，并支持将抑制MMP作为HIV-结核病的宿主导向治疗策略。

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Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis.

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.

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来源期刊

Journal of Infectious Diseases 医学-传染病学

CiteScore

13.50

自引率

3.10%

发文量

449

审稿时长

2-4 weeks

期刊介绍： Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.