-
梅毒是由梅毒螺旋体感染所致的慢性性传播疾病,是我国目前发病率最高的性传播疾病之一,主要通过性交传染,也可通过母体子宫垂直传播,引起新生儿先天梅毒[1]。关于梅毒的治疗虽然有标准的诊治指南,但复发率仍较高。研究[2]表明,机体的免疫功能在清除梅毒螺旋体过程中发挥重要作用,免疫功能受抑制是梅毒病程迁延、反复发作的重要原因。T淋巴细胞免疫球蛋白黏蛋白分子-3(T-cell immunoglobulin domain and mucin domain-containing molecule 3,Tim-3)是T细胞免疫球蛋白黏蛋白家族中的一员,通过多种途径调节机体免疫应答,在多种疾病的病情发展中发挥作用[3]。本文通过分析梅毒病人血清Tim-3表达水平,并检测体液免疫功能指标及T淋巴细胞亚群表达变化,同时分析治疗前后Tim-3水平变化,探讨Tim-3在梅毒病程进展中的作用。
-
梅毒组病人血清Tim-3、IgG、IgM、IgA水平明显高于对照组(P < 0.01)。梅毒组病人CD4+ T细胞水平、CD4+/CD8+值均明显低于对照组(P < 0.01),CD8+ T细胞水平明显高于对照组(P < 0.01)(见表 1)。
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 梅毒组 105 16.19±3.79 16.54±3.48 3.23±0.67 1.53±0.30 38.19±4.59 27.73±3.67 1.41±0.31 对照组 30 11.54±3.22 13.77±2.84 2.44±0.35 1.26±0.26 43.06±5.11 22.88±3.13 1.94±0.47 t — 6.11 3.99 6.21 4.47 5.00 6.59 7.29 P — < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 表 1 2组病人血清Tim-3水平、体液免疫指标及T淋巴细胞亚群水平比较(x±s)
-
一期、二期、三期梅毒组Tim-3水平高于隐性组(P < 0.05~P < 0.01);二期、三期梅毒组Tim-3水平高于一期梅毒组(P < 0.05~P < 0.01)。三期梅毒组血清IgM明显高于一期梅毒组和隐性组(P < 0.01);二期、三期梅毒组IgA水平高于一期梅毒组(P < 0.05)。二期、三期梅毒组CD4+ T细胞水平、CD4+/CD8+值明显降低于隐性组(P < 0.01),CD8+ T细胞水平明显高于隐性组(P < 0.01)(见表 2)。
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 一期组 26 16.22±3.02 16.02±3.46 3.19±0.62 1.41±0.33 37.67±3.83 28.45±3.55 1.32±0.25 二期组 27 18.48±3.99* 17.09±3.94 3.58±0.58* 1.66±0.25* 35.54±4.55 30.04 ±3.10 1.19±0.18* 三期组 21 19.56±4.24** 17.92±4.01 3.7±0.66** 1.68±0.34* 34.86±4.23 30.88±4.88 1.14±0.21* 隐性组 31 14.18±3.08*##▲▲ 15.94±3.07 2.94±0.46##▲▲ 1.52±0.28 40.93±3.72**##▲▲ 25.10±2.46**##▲▲ 1.65±0.27**##▲▲ F — 11.97 1.68 11.44 4.51 12.35 14.85 27.25 P — < 0.01 >0.05 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 MS组内 — 12.733 12.943 0.331 0.089 16.614 12.107 0.054 q检验:与一期组比较*P < 0.05,**P < 0.01;与二期组比较##P < 0.01;与三期组比较▲▲P < 0.01 表 2 不同分期梅毒病人血清Tim-3水平、体液免疫功能指标及T淋巴细胞亚群水平比较(x±s)
-
梅毒病人治疗前后血清IgG水平变化差异无统计学意义(P>0.05)。治疗后血清Tim-3水平和外周血CD8+ T细胞水平明显低于治疗前(P < 0.01),外周血CD4+ T细胞水平、CD4+/CD8+值均明显高于治疗前(P < 0.01)(见表 3)。
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 治疗前 74 17.99±3.95 16.92±3.83 3.51±0.72 1.59±0.33 36.09±4.33 29.72±3.91 1.23±0.25 治疗后 74 14.98±3.91 15.88±3.96 3.12±0.63 1.43±0.33 39.29±4.68 26.82±3.75 1.52±0.31 t — 4.66 1.62 3.51 2.95 4.32 4.60 6.26 P — < 0.01 >0.05 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 表 3 梅毒病人治疗前后血清Tim-3水平、体液免疫功能指标及T淋巴细胞亚群水平比较(x±s)
-
Pearson相关分析, 显示梅毒螺旋体感染者Tim-3水平与CD8+T细胞水平呈正相关关系(r=0.52,P < 0.05),与CD4+T细胞水平呈负相关关系(r=-0.46,P < 0.05);Tim-3水平与IgG、IgM、IgA无明显相关关系(P>0.05)。
梅毒螺旋体感染者血清Tim-3水平与机体免疫功能相关性分析
Analysis on the relationship between the serum level of Tim-3 and immune function in treponemia pallidum infection patients
-
摘要:
目的分析梅毒螺旋体感染者血清T淋巴细胞免疫球蛋白黏蛋白分子-3(Tim-3)水平,探讨其与机体免疫功能的相关性。 方法选择梅毒螺旋体感染者105例,其中一期梅毒病人26例、二期梅毒病人27例、三期梅毒病人21例、隐性梅毒病人31例,另选择30名健康体检者作为对照组,检测各组血清Tim-3水平、体液免疫功能指标及T淋巴细胞亚群水平,并检测活动期梅毒治疗后血清Tim-3水平变化。 结果梅毒组病人血清Tim-3、IgG、IgM、IgA水平明显高于对照组(P < 0.01);二期、三期梅毒组Tim-3水平高于一期梅毒组和隐性组(P < 0.05~P < 0.01)。梅毒组病人CD4+ T细胞水平、CD4+/CD8+值均明显低于对照组(P < 0.01),CD8+ T细胞水平明显高于对照组(P < 0.01)。活动期梅毒经正规驱梅治疗后,血清Tim-3水平和外周血CD8+ T细胞水平明显低于治疗前(P < 0.01),外周血CD4+ T细胞水平、CD4+/CD8+值均明显高于治疗前(P < 0.01)。Pearson相关分析显示,梅毒螺旋体感染者Tim-3水平与CD8+ T细胞水平呈正相关关系(r=0.52,P < 0.05),与CD4+ T细胞水平呈负相关关系(r=-0.46,P < 0.05),与IgG、IgM、IgA无明显相关关系(P>0.05)。 结论梅毒螺旋体感染者存在Tim-3水平的升高、体液免疫功能的亢进及细胞免疫功能的失衡,血清Tim-3水平与CD4+、CD8+ T细胞水平存在相关性,可能参与了梅毒细胞免疫功能紊乱的过程,加速了病程进展。 -
关键词:
- 梅毒 /
- T淋巴细胞免疫球蛋白黏蛋白分子-3 /
- 体液免疫 /
- T淋巴细胞亚群
Abstract:ObjectiveTo analyze the serum level of T-cell immunoglobulin domain and mucin domain-containing molecule 3(Tim-3) in treponemia pallidum infection patients, and explore its correlation with immune function. MethodsOne hundred and five patients with ponemia pallidum infection included 26 cases of primary syphilis, 27 cases of secondary syphilis, 21 cases of third syphilis and 31 cases of latent syphilis, and 30 healthy subjects were set as the control group.The serum levels of Tim-3, humoral immunity index and T lymphocyte subgroup in all subjects were detected.The serum level of Tim-3 in active syphilis patients were detected after treatment. ResultsThe serum levels of Tim-3, IgG, IgM and IgA in treponemia pallidum infection groups were higher than those in control group(P < 0.01), and the serum levels of Tim-3 in secondary and third syphilis groups were significantly higher than those in primary and latent syphilis groups(P < 0.05 to P < 0.01).The CD4+T cell level and ratio of CD4+/CD8+ in patients with syphilis were significantly lower than those in control group(P < 0.01), while the CD8+T cell level in patients with syphilis was significantly higher than that in control group(P < 0.01).After regular syphilis depravation treatment for active syphilis, the serum levels of Tim-3 and peripheral blood CD8+ T cell were significantly lower than those before treatment(P < 0.01), and the peripheral blood CD4+ T cell level and CD4+/CD8+ value were significantly higher than those before treatment(P < 0.01).The results of Pearson correlation analysis showed that the level of Tim-3 was positively correlated with the level of CD8+ T cells(r=0.52, P < 0.05), negatively correlated with level of CD4+ T cells(r=-0.46, P < 0.05), but not significantly correlated with IgG, IgM and IgA(P>0.05). ConclusionsThe Tim-3 level increasing, hyperhumoral immune function and imbalance of cellular immune function exist in the patients infected with treponema pallidum.The serum level of Tim-3 is correlated with the CD4+ and CD8+ T cell levels, which may be involved in the process of cellular immune dysfunction of syphilis and accelerating the course of the disease. -
表 1 2组病人血清Tim-3水平、体液免疫指标及T淋巴细胞亚群水平比较(x±s)
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 梅毒组 105 16.19±3.79 16.54±3.48 3.23±0.67 1.53±0.30 38.19±4.59 27.73±3.67 1.41±0.31 对照组 30 11.54±3.22 13.77±2.84 2.44±0.35 1.26±0.26 43.06±5.11 22.88±3.13 1.94±0.47 t — 6.11 3.99 6.21 4.47 5.00 6.59 7.29 P — < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 表 2 不同分期梅毒病人血清Tim-3水平、体液免疫功能指标及T淋巴细胞亚群水平比较(x±s)
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 一期组 26 16.22±3.02 16.02±3.46 3.19±0.62 1.41±0.33 37.67±3.83 28.45±3.55 1.32±0.25 二期组 27 18.48±3.99* 17.09±3.94 3.58±0.58* 1.66±0.25* 35.54±4.55 30.04 ±3.10 1.19±0.18* 三期组 21 19.56±4.24** 17.92±4.01 3.7±0.66** 1.68±0.34* 34.86±4.23 30.88±4.88 1.14±0.21* 隐性组 31 14.18±3.08*##▲▲ 15.94±3.07 2.94±0.46##▲▲ 1.52±0.28 40.93±3.72**##▲▲ 25.10±2.46**##▲▲ 1.65±0.27**##▲▲ F — 11.97 1.68 11.44 4.51 12.35 14.85 27.25 P — < 0.01 >0.05 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 MS组内 — 12.733 12.943 0.331 0.089 16.614 12.107 0.054 q检验:与一期组比较*P < 0.05,**P < 0.01;与二期组比较##P < 0.01;与三期组比较▲▲P < 0.01 表 3 梅毒病人治疗前后血清Tim-3水平、体液免疫功能指标及T淋巴细胞亚群水平比较(x±s)
分组 n Tim-3/(pg/mL) IgG/(mg/dL) IgM/(mg/dL) IgA/(mg/dL) CD4+/% CD8+/% CD4+/CD8+ 治疗前 74 17.99±3.95 16.92±3.83 3.51±0.72 1.59±0.33 36.09±4.33 29.72±3.91 1.23±0.25 治疗后 74 14.98±3.91 15.88±3.96 3.12±0.63 1.43±0.33 39.29±4.68 26.82±3.75 1.52±0.31 t — 4.66 1.62 3.51 2.95 4.32 4.60 6.26 P — < 0.01 >0.05 < 0.01 < 0.01 < 0.01 < 0.01 < 0.01 -
[1] 张荣, 吴岷岷, 华云晖. 先天性梅毒56例临床分析[J]. 蚌埠医学院学报, 2012, 37(12): 1499. [2] INGRAM B. The many presentations of syphilis[J]. Dermatol Nurses Assoc, 2018, 10(5): 239. doi: 10.1097/JDN.0000000000000431 [3] DIXON KO, DAS M, KUCHROO VK. Human disease mutations highlight the inhibitory function of Tim-3[J]. Nat Genet, 2018, 50(12): 1640. doi: 10.1038/s41588-018-0289-3 [4] CABELLO A, GORGOLAS M. Syphilis. Status of a current epidemic[J]. Med Clin(Barc), 2017, 149(12): 540. [5] 王千秋, 范瑞强. 梅毒血清固定临床处理专家共识[J]. 中华皮肤科杂志, 2015, 48(11): 753. [6] MONSEL G, PALICH R, CAUMESÉ. Syphilis: what's new?[J]. Rev Prat, 2018, 68(8): 881. [7] CHEN YY, QIU XH, ZHANG YF, et al. A better definition of active syphilis infection[J]. Clin Chim Acta, 2015, 444(12): 1. [8] MALM K, ANDERSSON S, FREDLUND H, et al. Analytical evaluation of nine serological assays for diagnosis of syphilis[J]. J Eur Acad Dermatol Venereol, 2015, 29(12): 2369. doi: 10.1111/jdv.13237 [9] QIU MK, WANG SC, DAI YX, et al. PD-1 and Tim-3 pathways regulate CD8+ T cells function in atherosclerosis[J]. PLoS One, 2015, 10(6): e0128523. doi: 10.1371/journal.pone.0128523 [10] GORMAN JV, COLPAN JD. Acute stimulation generates Tim-3-expressing T helper type 1 CD4 T cells that persist in vivo and show enhanced effector function[J]. Immunology, 2018, 154(3): 418. doi: 10.1111/imm.12890 [11] JIN HT, ANDERSON AC, TAN WG, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection[J]. Proc Natl Acad Sci USA, 2010, 107(33): 14733. doi: 10.1073/pnas.1009731107 [12] LIU Y, GAO LF, LIANG XH, et al. Role of Tim-3 in hepatitis B virus infection: An overview[J]. World J Gastroenterol, 2016, 22(7): 2294. doi: 10.3748/wjg.v22.i7.2294 [13] RALLON N, GARCIA M, GARCIA-SAMANIEGO J, et al. Expression of PD-1 and Tim-3 markers of T-cell exhaustion is associated with CD4 dynamics during the course of untreated and treated HIV infection[J]. PLoS One, 2018, 13(3): e0193829. doi: 10.1371/journal.pone.0193829 [14] PEI JP, JIANG LF, JI XW, et al. The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection[J]. Eur J Clin Microbiol Infect Dis, 2016, 35(8): 1377. doi: 10.1007/s10096-016-2676-y [15] LIN M, HUANG J, HUANG J, et al. Level of serum soluble Tim-3 expression in early-phase acute pancreatitis[J]. Turk J Gastroenterol, 2019, 30(2): 188. doi: 10.5152/tjg.2018.18137 [16] 刘宏业, 韩燕, 尹跃平. 梅毒免疫和梅毒螺旋体的研究进展[J]. 国际皮肤性病学杂志, 2016, 42(6): 490.