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肺结核患者和家庭接触者的血清铁水平及其与天然抗性相关巨噬细胞蛋白 1 多态性和表达的关系。

Serum iron levels in tuberculosis patients and household contacts and its association with natural resistance-associated macrophage protein 1 polymorphism and expression.

机构信息

Pusat Kebijakan Sumber Daya dan Sistem Ketahanan Kesehatan, Badan Kebijakan Pembangunan Kesehatan, Ministry of Health Republic Indonesia, Jakarta, Indonesia.

Postgraduate Program, Faculty of Medicine, Universitas Hasanuddin, Makassar, South Sulawesi, Indonesia.

出版信息

Clin Respir J. 2023 Sep;17(9):893-904. doi: 10.1111/crj.13677. Epub 2023 Aug 22.

Abstract

BACKGROUND

Iron deficiency can impair immune function, increasing tuberculosis (TB) susceptibility and severity. The research aimed to investigate iron deficiency anemia in TB patients and household contacts and its association with natural resistance-associated macrophage protein 1 (NRAMP1) polymorphism and expression.

METHODS

The levels of iron, ferritin, and transferrin were measured in the serum by ELISA (Enzyme-Linked Immunosorbent Assay). NRAMP1 polymorphisms were determined by polymerase chain reaction (PCR) and sequencing. NRAMP1 gene expression was measured by real-time PCR. Interferon-gamma release assay (IGRA) checked on household contacts to screen household contacts with positive IGRA as the control.

RESULTS

This study involved 35 TB cases and 35 TB contacts. The results showed that the serum Fe levels were found to be lower in the TB case group (median 149.6 μmol/L) than in the positive IGRA household contacts group (median 628.53 μmol/L) with a p-value <0.001. Meanwhile, ferritin levels in TB cases tended to be higher, in contrast to transferrin, which was found to tend to be lower in TB cases than household contacts but did not show a significant difference. This study found no association between the polymorphism of exon 15 D543 and active TB. However, NRAMP1 gene expression was lower in TB cases than in positive IGRA household contacts (p = 0.011). Besides, there was a positive correlation between NRAMP1 gene expression and serum Fe levels (r = 0.367, p = 0.006). TB was associated with decreased NRAMP1 gene expression (OR 0.086 95% CI 0.02-0.366, p = 0.001). Besides, TB was associated with low Fe levels (OR 0.533 95% CI 0.453-0.629, p < 0.001).

CONCLUSION

Comparing the TB case to the household contacts group, decreased serum Fe levels were discovered in the TB case group. This study also shows a correlation of NRAMP1 gene expression to Fe levels in TB patients and household contacts and describes that TB may lead to decreased Fe levels by downregulating NRAMP1 expression.

摘要

背景

铁缺乏可损害免疫功能,增加结核病(TB)的易感性和严重程度。本研究旨在探讨 TB 患者和家庭接触者的缺铁性贫血及其与天然抗性相关巨噬细胞蛋白 1(NRAMP1)多态性和表达的关系。

方法

采用酶联免疫吸附试验(ELISA)检测血清中铁、铁蛋白和转铁蛋白的水平。采用聚合酶链反应(PCR)和测序法检测 NRAMP1 多态性。采用实时 PCR 法检测 NRAMP1 基因表达。对家庭接触者进行干扰素-γ释放试验(IGRA)检查,以筛选出 IGRA 阳性的家庭接触者作为对照组。

结果

本研究共纳入 35 例 TB 病例和 35 例 TB 接触者。结果显示,TB 病例组的血清 Fe 水平明显低于阳性 IGRA 家庭接触者组(中位数 149.6 μmol/L),差异具有统计学意义(p<0.001)。同时,TB 病例组的铁蛋白水平较高,而转铁蛋白水平较低,但差异无统计学意义。本研究未发现外显子 15 D543 多态性与活动性 TB 之间存在关联。然而,TB 病例组的 NRAMP1 基因表达低于阳性 IGRA 家庭接触者(p=0.011)。此外,NRAMP1 基因表达与血清 Fe 水平呈正相关(r=0.367,p=0.006)。TB 与 NRAMP1 基因表达降低相关(OR 0.086,95%CI 0.02-0.366,p=0.001)。此外,TB 与低 Fe 水平相关(OR 0.533,95%CI 0.453-0.629,p<0.001)。

结论

与家庭接触者组相比,TB 病例组的血清 Fe 水平降低。本研究还表明,NRAMP1 基因表达与 TB 患者和家庭接触者的 Fe 水平相关,并描述了 TB 可能通过下调 NRAMP1 表达导致 Fe 水平降低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a3b/10500328/0fb5ee980aff/CRJ-17-893-g003.jpg

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