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-β was 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-β increased 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-β was 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-β in 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-β are closely related to the pathogenesis and activity of vitiligo.
目的:采用两种蛋白质组学技术鉴定和筛选不同分期白癜风的血清标志物,并研究其网络关系.方法:收集白癜风稳定期和进展期以及健康人各15例的血清样本,采用双向凝胶电泳技术(2-DE)和核素标记相对和绝对定量技术(iTRAQ)对所有样本进行检测,筛选出差异表达蛋白,并用软件分析其可能作用的主要通路.结果:通过2-DE鉴定出稳定期白癜风患者10个差异蛋白(6个上调,4个下调),进展期白癜风患者25个差异蛋白(11个上调,14个下调);iTRAQ鉴定出稳定期患者62个差异蛋白(29个上调,33个下调),进展期患者50个差异蛋白(30个上调,20个下调).两种蛋白质组学鉴定出的相同差异蛋白包括稳定期间α-胰蛋白酶抑制剂重链H4、补体C4-A(上调);进展期补体C4-B、载脂蛋白A(下调)和间α-胰蛋白酶抑制剂重链H4(上调).基因本体(Gene ontology,GO)注释分析示共同的差异蛋白主要参与CCKR通路、纤溶酶原激活级联通路、p53通路、趋化炎症因子调控通路等.结论:基于2-DE与iTRAQ两种不同的蛋白质组学方法筛选出不同分期白癜风的共同差异表达蛋白,为进一步研究白癜风的发生机制奠定了基础.
Xinghua Gao (高兴华)合作论文数Institute of Health Sciences, China Medical University;The First Hospital of China Medical University1