白癜风外周血中MBL和Treg细胞及其因子水平变化的相关性分析

Comparison and correlation of MBL and Treg cells and their related factors in peripheral blood of vitiligo

目的探讨白癜风患者不同分期分型中血清甘露糖结合凝结素(mannose/mannan-binding lectin,MBL)、调节性T细胞(regulatory T cell,Treg)和其细胞因子的变化及与其活动度的相关性。方法选择2020年10月至2021年6月复旦大学附属中山医院确诊的50例白癜风患者为研究对象,根据白癜风临床分期标准分为稳定期(25例)和进展期(25例);根据白癜风临床分型原则分为节段型(14例)和非节段型(36例)。另选择25例健康体检者为对照组。比较不同分期、分型与对照组的外周血MBL、CD4^(+)CD25^(+)CD127-Treg细胞及细胞毒T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)、白细胞介素(interleukin,IL)-10,转化生长因子-β(transforming growth factor-β,TGF-β)的变化,并分析白癜风患者病情活动程度(vitiligo disease activity score,VIDA)与MBL等指标的相关性。结果与对照组相比,稳定期及进展期白癜风患者血清MBL、外周血单个核细胞(peripheral blood mononuclear cell,PBMC)中CD4^(+)CD25^(+)CD127-Treg细胞及相关因子CD4^(+)CD25^(+)CD152^(+)(CTLA-4)水平明显降低,TGF-β水平明显升高,组间差异具有统计学意义[ng/mL:(4.76±0.56)比(4.32±0.56)比(3.80±0.43),%:(7.51±3.28)比(6.21±1.52)比(4.02±0.68),%:(4.04±1.84)比(4.00±2.04)比(2.36±1.08),ng/mL:(32.17±14.49)比(50.79±22.40)比(66.40±27.04),F=20.78、17.12、7.88、15.27,P值均<0.05],而IL-10表达的组间差异无统计学意义(P>0.05)。与稳定期相比,进展期MBL、Treg细胞及相关因子CTLA-4水平明显降低,TGF-β水平明显升高,组间差异具有统计学意义(P=0.001、0.001、0.003)。与对照组相比,节段型与非节段型白癜风患者血清MBL及CD4^(+)CD25^(+)CD127-Treg细胞水平明显降低,TGF-β表达明显升高,差异具有统计学意义[ng/mL:(4.76±0.56)比(3.95±0.61)比(4.14±0.55),%:(7.51±3.28)比(5.49±1.48)比(4.97±1.65),ng/mL:(30.89±17.88)比(58.08±30.14)比(59.32±23.99),F=12.26、9.19、11.96,P值均<0.05],而相关因子CD4^(+)CD25^(+)CD152^(+)(CTLA-4)和IL-10表达的组间差异无统计学意义(P>0.05)。相关性分析结果显示,白癜风患者VIDA评分与MBL及CD4^(+)CD25^(+)CD127-Treg细胞水平呈显著负相关,与TGF-β呈显著正相关(r=-0.28、-0.36、0.31,P值均<0.05)。结论MBL、Treg及其细胞因子CTLA-4、TGF-β与白癜风的发病进程及其活动度密切相关。

Objective To investigate the changes of serum mannose-binding lectin(MBL)and regulatory T cell(Treg)and their cytokines in patients with vitiligo at different stages and types,and their correlation with their activity.Methods A total of 50 patients with vitiligo diagnosed in Zhongshan Hospital Fudan University from October 2020 to June 2021 were selected.According to the clinical staging criteria of vitiligo,they were divided into stable stage(25 cases)and progressive stage(25 cases).According to the clinical classification principle,they were divided into segmental type(14 cases)and non-segmental type(36 cases).Another 25 healthy subjects were selected as the control group.The changes of MBL,CD4^(+)CD25^(+)CD127-Treg,related factors cytotoxic T lymphocyte-associated antigen-4(CTLA-4),interleukin(IL)-10 and transforming growth factor-β(TGF-β)in peripheral blood of patients with vitiligo were compared among the control group and different stages and types,and the correlation between vitiligo disease activity score(VIDA)and related indicators was analyzed.Results Compared with the control group,the levels of serum MBL,CD4^(+)CD25^(+)CD127-Treg cells and related factor CD4^(+)CD25^(+)CD152^(+)(CTLA-4)in peripheral blood mononuclear cell(PBMC)of patients with stable and progressive vitiligo were significantly lower,while the level of TGF-βwas significantly higher[ng/mL:(4.76±0.56)vs(4.32±0.56)vs(3.80±0.43),%:(7.51±3.28)vs(6.21±1.52)vs(4.02±0.68),%:(4.04±1.84)vs(4.00±2.04)vs(2.36±1.08),ng/mL:(32.17±14.49)vs(50.79±22.40)vs(66.40±27.04),F=20.78,17.12,7.88,15.27,all P values<0.05].However,there was no significant difference in IL-10 expression among the groups(P>0.05).Compared with the stable phase,the CTLA-4 levels of MBL,Treg cells and related factors decreased significantly,while the level of TGF-βincreased significantly(P=0.001,0.001,0.003).Compared with the control group,the levels of serum MBL and CD4^(+)CD25^(+)CD127-Treg cells in patients with segmental vitiligo and non-segmental vitiligo were significantly lower,and the expression of TGF-βwas significantly higher[ng/mL:(4.76±0.56)vs(3.95±0.61)vs(4.14±0.55),%:(7.51±3.28)vs(5.49±1.48)vs(4.97±1.65),ng/mL:(30.89±17.88)vs(58.08±30.14)vs(59.32±23.99),F=12.26,9.19,11.96,all P values<0.05)].There was no significant difference in the expression of CD4^(+)CD25^(+)CD152^(+)(CTLA-4)and IL-10 among the groups(P>0.05).VIDA score was negatively correlated with MBL and Treg,and positively correlated with TGF-βin patients with vitiligo(r=-0.28、-0.36、0.31,all P values<0.05).Conclusion MBL,Treg and their cytokines CTLA-4 and TGF-βare closely related to the pathogenesis and activity of vitiligo.