布鲁菌病患者CD4^(+)T细胞Tim-3及其相关细胞因子的表达及临床意义

Expression and clinical significance of Tim-3 and its related cytokines on CD4+T cells in patients with brucellosis

目的探讨布鲁菌病(brucellosis melitensis,Bm,简称布病)患者T细胞表面T细胞免疫球蛋白和黏蛋白结构域蛋白3(T cell immunoglobulin and mucin domain-containing protein 3,Tim-3)以及血清中白细胞介素-10(interleukin-10,IL-10)和转化生长因子-β(transforming growth factor beta,TGF-β)的表达情况,分析这些指标在急慢性期患者中的表达差异,为急慢性期布病鉴别诊断提供新方案。方法选取2023年4—9月在新疆医科大学第一附属医院确诊为布鲁菌病患者56例,其中31例为急性期患者,25例为慢性期患者。同期35例健康体检者为健康对照。运用流式细胞术检测并比较各组CD4+T细胞表面Tim-3水平,运用流式液相多重蛋白定量实验(cytometric bead array,CBA)和酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)检测并比较各组血清中IL-10和TGF-β的水平,并分析这些因素与布病患者分期的关系。结果对照组、急性组和慢性组的Tim-3^(+)CD3^(+)CD4^(+)T细胞占比分别为(2.56±1.25)%、(5.14±1.98)%和(13.66±2.66)%,患者组的Tim-3水平较健康对照组高,且慢性组更高,差异有统计学意义(P<0.05)。患者组的IL-10和TGF-β水平较健康对照组高,且慢性组IL-10、TGF-β水平均明显高于急性组,差异有统计学意义(P<0.05)。Tim-3、IL-10和TGF-β评分预测布病患者慢性期的受试者工作特征(receiver operating characteristic,ROC)曲线下面积分别为0.876、0.865、0.663。结论Tim-3以及血清IL-10和TGF-β在布病患者中表达存在一定的差异性,Tim-3、IL-10和TGF-β高表达提示患者有可能转变为布病慢性期,且Tim-3的诊断效果最好。因此,Tim-3作为诊断指标可能为布病的治疗与鉴别诊断提供新的思路和策略。

Objective To investigate the expression of T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)on the surface of T cells in patients with brucellosis(Bm),as well as the expression of interleukin-10(IL-10)and transforming growth factor beta(TGF-β)in serum,and to analyze the differential expression of these indicators in patients with acute and chronic brucellosis,in order to provide new approaches for the differential diagnosis of acute and chronic brucellosis.Methods A total of 56 patients diagnosed with brucellosis at the First Affiliated Hospital of Xinjiang Medical University from April 2023 to September 2023 were selected,including 31 patients in the acute phase and 25 patients in the chronic phase.Additionally,35 healthy individuals underwent routine physical examinations within the same period served as healthy controls.Flow cytometry was used to detect and compare Tim-3 levels on the CD4^(+)T cells'surface among the groups.Levels of serum IL-10 and TGF-βwere measured and compared using CBA and ELISA,respectively,and the relationship of these factors with the staging of brucellosis patients was analyzed.Results The proportions of Tim-3^(+)CD3^(+)CD4^(+)T cells in the control group,acute group,and chronic group were(2.56±1.25)%,(5.14±1.98)%,and(13.66±2.66)%,respectively.The Tim-3 levels in the patients with brucellosis were higher than those in the healthy control group,with the chronic group showing even higher levels,and these differences were statistically significant(P<0.05).The levels of IL-10 and TGF in the patient group were higher than those in the healthy control group,with the chronic group exhibiting significantly higher levels of IL-10 and TGF-βthan the acute group,also presenting statistically significant differences(P<0.05).The areas under the ROC curve for predicting chronic brucellosis with Tim-3,IL-10,and TGF-βscores were 0.876,0.865,and 0.663,respectively.Conclusions There are certain differences in the expression of Tim-3,serum IL-10,and TGF-βamong patients with brucellosis,with high expression indicating a potential transition to the chronic phase of the disease.Tim-3 has shown the best diagnostic performance.Therefore,as a diagnostic indicator,Tim-3 may provide new ideas and strategies for the treatment and differential diagnosis of brucellosis.