Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
PLoS One. 2015 Jan 30;10(1):e0117605. doi: 10.1371/journal.pone.0117605. eCollection 2015.
Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.
结核病（TB）仍然是一种全球健康大流行疾病，需要深入了解潜在的发病机制，以开发新的治疗和诊断方法。基质金属蛋白酶（MMPs）是结核病组织破坏的关键效应因子，但尚未在血浆中进行全面研究，也未研究性别差异。我们在一个精心描述的、前瞻性招募的 380 名个体临床队列中测量了 MMPs 的血浆浓度。胶原酶 MMP-1 和 MMP-8 在肺结核患者的血浆中升高，相对健康对照组升高，MMP-7（基质溶解素）和 MMP-9（明胶酶 B）也升高。MMP-8 是结核病特异性的（p<0.001），在有症状的对照组中不升高（症状疑似结核病，但排除活动期疾病）。MMP-8 与体质指数呈负相关。男性结核病患者的 MMP-8 血浆浓度比女性高 1.51 倍（p<0.05），而这种差异并非由于男性疾病严重程度更大。MMPs 的性别特异性分析表明，在结核病中 MMP-1 和 MMP-8 均增加，但 MMP-8 是男性结核病的更好鉴别标志物。肺结核患者的血浆胶原酶升高，且在男性和女性之间存在差异。在研究结核病免疫病理学和开发新的诊断标志物时，必须考虑性别因素。
