辅助性T细胞和调节性T细胞在天疱疮发病中的作用

Role of Th17 and Treg cells in the pathogenesis of pemphigus

目的:探讨辅助性T细胞17(Th17)和调节性T(Treg)细胞在天疱疮发病中的免疫介导机制。方法:采用FACS检测51例天疱疮患者外周血中CD3^+CD8^-T细胞(即CD3^+CD4^+T细胞)IL-17A表达,以及CD4^+CD25hiFoxp3^+Treg细胞水平,并与26例正常对照比较;采用ELISA法检测患者血清中特异性抗桥粒芯糖蛋白(Dsg)1、Dsg3抗体滴度、亚型,分析其与Th17和Treg细胞相关性。结果:天疱疮患者外周血Th17细胞比例显著高于正常对照组(P=0.014),并且急性期升高更为明显,急性期显著高于正常对照组(P=0.015);患者外周血Treg细胞比例显著低于正常对照组(P<0.001),并且急性期和稳定期患者均显著低于正常对照(P值分别为<0.001和=0.015),同时急性期患者显著低于稳定期患者(P=0.024);天疱疮患者外周血Th17与Treg细胞比例呈负相关(r=-0.532,P<0.001)。急性期患者抗Dsg1和Dsg3抗体滴度水平显著高于稳定期,并且急性期患者抗体亚型IgG4/IgG1比值显著升高。Dsg1和Dsg3抗体滴度水平及抗体亚型与Th17和Treg细胞比例无相关性。结论:天疱疮患者外周血Th17与Treg细胞失平衡,参与天疱疮致病。急性期患者抗体滴度显著升高,其中IgG4亚型是主要的致病性抗体。

Objective： To investigate the role of Th17 and Treg （regulatory T） cells in immune mediated mechanism of pem- phigus＇s pathogenesis. Methods： Peripheral blood mononuclear cells were prepared from 51 patients with pemphigus as well as 26 normal controls, and the frequencies of Th17 cells （CD3＋CDS-IL-17A＋, ie, CD3＋CD4＋IL-17A＋） and Treg cells（CD4＋ CD25hiFoxp3＋） were determined by flow cytometry. Serum specific Dsgl, Dsg3 antibodies and subtypes of patients were detected by ELISA. And the relationship of Th17 cells, Treg cells and the antibodies were analysised. Results： Peripheral blood from pemphigus patients showed significantly higher levels of Th17 cells than that from normal controls （P= 0.014）, specially in acute phase of pemphigus （P= 0.015 vs. normal control）; The levels of Treg cells in both acute and stable phases of pemphigus were significantly lower than that in normal control group （P〈0.001 for acute and P〈0.05 for stable）; Moreover, the levels of Treg cells were lower in acute than in stable pemphigus （P= 0.024）. The levels of Th17 cells in peripheral blood of patients with pemphigus were negatively correlated with the levels of Treg cells （r =-0.532, P 〈 0.001）. Anti-Dsgl and -Dsg3 antibody titers were higher in acute phase than that in stable phase patients. Subtype antibody ratio of IgG4 to IgG1 increased in acute phase. Dsgl and Dsg3 antibody titers, and subtype antibody didn＇t show any correlation with Th17 and Treg cells. Conclusion： Imbalance of Th17 and Treg ceils in peripheral blood of pemphigus patients involves in pathogenesis of pemphigus. Antibody titers rise significantly during acute phase, and IgG4 subtype plays an important role in the pathogenesis of pemphigus.