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维生素D对肺结核患者密切家庭接触者活动性肺结核发病的保护作用:一项前瞻性队列研究

Protective Role of Vitamin D Against Development of Active Tuberculosis in Close Household Contacts of Pulmonary Tuberculosis Patients: A Prospective Cohort Study.

作者信息

Panda Sudhasini, Tiwari Ambrish, Kumar Vivek, Luthra Kalpana, Kumar Kuldeep, Singh Archana

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110029 India.

Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, 110029 India.

出版信息

Indian J Clin Biochem. 2024 Apr;39(2):248-256. doi: 10.1007/s12291-022-01110-3. Epub 2023 Jan 12.

Abstract

Vitamin-D is known to promote innate immune responses by acting as a cofactor of VDR for induction of antimicrobial peptides like cathelicidin. Close household contacts of pulmonary tuberculosis patients are at high risk of active infection, Therefore, possible role of vitamin-D in TB prevention through cathelicidin production was studied in high-risk household contacts (HHCs) of pulmonary tuberculosis (PTB) patients. 20 HHCs of PTB patients were recruited and followed up for one year. Levels of vitamin-D (25(OH)D) and its associated molecules were evaluated at 3-months intervals for one year or until the development of active TB. 25(OH)D was measured using chemiluminescence method. Serum VDR and cathelicidin levels were measured by ELISA and VDR mRNA expression by qPCR. Throughout the study period mean range of serum 25(OH)D levels was 20.51 ± 5.12 ng/ml. VDR and cathelicidin levels however showed significant decline after six months suggesting decrease in bacterial exposure. None of the HHCs developed active infection even with high exposure to 2 + to 3 + AFB positive index cases. Mantoux positive household contacts had high levels of VDR and cathelicidin, suggestive of an early or latent phase of infection, did not develop active TB plausibly due to maintenance of adequate serum levels of vitamin-D. Optimal levels of 25(OH)D and its associated molecules during early stages of infection may serve as protective factor against development of active TB. Cohort of HHCs with severely deficient vitamin-D levels (10 ng/ml) could be followed up for a better risk assessment.

摘要

众所周知,维生素D作为维生素D受体(VDR)的辅助因子,通过诱导抗菌肽(如cathelicidin)来促进先天免疫反应。肺结核患者的密切家庭接触者有很高的活动性感染风险。因此,研究了维生素D在肺结核(PTB)患者的高危家庭接触者(HHCs)中通过cathelicidin产生来预防结核病的可能作用。招募了20名PTB患者的HHCs,并随访一年。在一年的时间里,每隔3个月评估一次维生素D(25(OH)D)及其相关分子的水平,直到出现活动性结核病。使用化学发光法测量25(OH)D。通过酶联免疫吸附测定(ELISA)测量血清VDR和cathelicidin水平,通过定量聚合酶链反应(qPCR)测量VDR mRNA表达。在整个研究期间,血清25(OH)D水平的平均范围为20.51±5.12 ng/ml。然而,VDR和cathelicidin水平在6个月后显著下降,表明细菌暴露减少。即使与2+至3+抗酸杆菌(AFB)阳性指数病例有高暴露接触,也没有HHCs发生活动性感染情况。结核菌素试验阳性的家庭接触者VDR和cathelicidin水平较高,提示处于感染的早期或潜伏阶段,由于维持了足够的血清维生素D水平,可能没有发展为活动性结核病。感染早期25(OH)D及其相关分子的最佳水平可能是预防活动性结核病发展的保护因素。对于维生素D水平严重缺乏(<10 ng/ml)的HHCs队列,可以进行随访以进行更好的风险评估。

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