Biotechnology Department, College of Science, University of Baghdad, Baghdad, Iraq.
National Specialized Center for Chest and Respiratory Diseases, Ministry of Health and Environment, Baghdad, Iraq.
Indian J Tuberc. 2022 Apr;69(2):191-200. doi: 10.1016/j.ijtb.2021.08.003. Epub 2021 Aug 12.
Control of tuberculosis (TB) depends on a balance between host's immune factors and bacterial evasion strategies. Interleukin-37 (IL-37) is among the immunomodulatory factors that have been proposed to influence susceptibility to tuberculosis.
A case-control study was conducted on 105 patients with pulmonary TB (37 active, 41 multi-drug resistant and 27 relapse) and 79 healthy controls to determine serum levels and single nucleotide polymorphisms (SNPs) of IL-37. The IL-37 level was assessed with an enzyme-linked immunosorbent kit, while DNA-sequencing was used to detect SNPs in the promoter region of IL37 gene.
Median level of IL-37 was markedly increased in serum of TB patients compared to controls (325.0 vs. 169.1 pg/mL; p < 0.001). This increase was universally determined in subgroups of patients distributed according to gender, age groups, and clinical type of disease, while no significant differences were found between the subgroups in patients or controls. Analysis of receiver operating characteristic curve confirmed these findings and IL-37 occupied a very good area under the curve, which was 0.816 (95% CI = 0.744-0.888; p < 0.001). At a cut-off value of 185.6 pg/mL, the sensitivity and specificity of IL-37 were 81.0 and 82.3%, respectively. Of the nine detected SNPs (rs2466449 G/A, rs2466450 A/G, rs2723168 G/A, rs3811042 G/A, rs3811045 T/C, rs3811046 G/T, rs3811047 A/G, rs3811048 G/A and rs200782323 G/A), only rs3811048 showed a significant association with TB; the G allele showed a significantly decreased frequency in TB patients compared to controls (25.2 vs. 44.9%; OR = 0.41; p < 0.001). It was possible to assign five haplotypes, and three showed significant differences between patients and controls. Frequency of haplotype A-A-G-A-C-T-G-A-G (0.331 vs. 0.213; OR = 2.10; p = 0.015) was significantly increased in TB patients compared to controls. On the contrary, frequencies of haplotypes A-A-G-A-C-T-G-G-G (0.029 vs. 0.116; OR = 0.24; p = 0.01) and A-A-G-G-T-G-A-G-G (0.140 vs. 0.275; OR = 0.45; p = 0.015) were significantly decreased in patients.
IL-37 was up-regulated in the serum of TB patients irrespective of their gender, age or clinical type of disease. SNPs in the promoter region of IL37 gene were proposed to be associated with susceptibility to TB.
结核病（TB）的控制取决于宿主免疫因素和细菌逃避策略之间的平衡。白细胞介素-37（IL-37）是影响结核病易感性的免疫调节因子之一。
对 105 例肺结核患者（37 例活动性、41 例耐多药、27 例复发）和 79 例健康对照进行病例对照研究，以确定血清中 IL-37 的水平和单核苷酸多态性（SNP）。采用酶联免疫吸附试剂盒检测 IL-37 水平，而 DNA 测序则用于检测 IL37 基因启动子区域的 SNP。
与对照组相比，肺结核患者血清中 IL-37 的中位水平明显升高（325.0 vs. 169.1 pg/mL；p < 0.001）。这种增加在按性别、年龄组和疾病临床类型分布的患者亚组中普遍存在，而在患者或对照组的亚组之间未发现显著差异。受试者工作特征曲线分析证实了这些发现，IL-37 曲线下面积非常好，为 0.816（95%CI=0.744-0.888；p < 0.001）。在 185.6 pg/mL 的截断值下，IL-37 的灵敏度和特异性分别为 81.0%和 82.3%。在检测到的 9 个 SNP 中（rs2466449 G/A、rs2466450 A/G、rs2723168 G/A、rs3811042 G/A、rs3811045 T/C、rs3811046 G/T、rs3811047 A/G、rs3811048 G/A 和 rs200782323 G/A），只有 rs3811048 与结核病显著相关；与对照组相比，G 等位基因在结核病患者中的频率显著降低（25.2% vs. 44.9%；OR=0.41；p < 0.001）。可以分配五个单倍型，其中三个在患者和对照组之间存在显著差异。与对照组相比，单倍型 A-A-G-A-C-T-G-A-G（0.331 对 0.213；OR=2.10；p=0.015）在结核病患者中的频率显著增加。相反，单倍型 A-A-G-A-C-T-G-G-G（0.029 对 0.116；OR=0.24；p=0.01）和 A-A-G-G-T-G-A-G-G-G（0.140 对 0.275；OR=0.45；p=0.015）的频率在患者中显著降低。
IL-37 在结核病患者的血清中呈上调状态，无论其性别、年龄或疾病临床类型如何。IL37 基因启动子区域的 SNP 被认为与结核病易感性相关。
