天疱疮患者调节性B细胞与致病性抗体的相关性研究

目的 探讨调节性B细胞（Breg）在天疱疮发病中的免疫介导机制。方法 以CD19+CD24hiCD38hi作为Breg标记，流式细胞仪检测48例天疱疮患者及20例健康人外周血中Breg占CD19+B细胞的比例，观察不同严重程度患者的Breg比例变化趋势。采用ELISA法检测患者血清中特异性抗Dsg1、Dsg3抗体滴度、亚型，分析其与Breg比例的相关性。结果 天疱疮患者外周血Breg占CD19+B细胞的比例（11.54% ± 0.97%）与健康对照组（8.19% ± 0.85%）相比差异有统计学意义（P = 0.04），且急性期轻度患者该比例（5.17% ± 2.14%）与中度患者（11.38% ± 5.30%，P = 0.042）、重度患者（11.17% ± 5.31%，P = 0.046）相比，差异均有统计学意义；Breg比例与抗Dsg1抗体亚型IgG4以及IgG4/IgG1的比值均呈正相关（r值分别为0.527，0.565，P值均 < 0.01）。 结论 Breg主要和抗体产生以及疾病活动相关，但其具体的作用机制尚待研究。

Relationship of regulatory B cells with pathogenic antibodies in pemphigus

Objective To explore the mechanisms underlying the mediating effect of regulatory B （Breg） cells in the pathogenesis of pemphigus. Methods Peripheral blood specimens were collected from 48 patients with pemphigus at different degrees of severity and 20 healthy controls. Flow cytometry was conducted to analyze the frequency of Breg （CD19+CD24hiCD38hi） cells in peripheral CD19+ B cells, enzyme linked immunosorbent assay （ELISA） to determine the titer and subtypes of anti-desmoglein （Dsg） 1 and 3 antibodies in sera from these subjects. The relationship of anti-Dsg 1 and 3 antibodies with the frequency of Breg cells was assessed by Spearman′s rank correlation test. Results Significant differences were observed in the proportion of Breg cells in CD19+ B cells between patients with pemphigus and healthy controls （11.54% ± 0.97% vs. 8.19% ± 0.85%, P = 0.04）, as well as between patients with acute mild pemphigus and those with moderate and severe pemphigus （5.17% ± 2.14% vs. 11.38% ± 5.30% and 11.17% ± 5.31%, P = 0.042, 0.046, respectively）. The frequency of Breg cells was positively correlated with the absorbance value for anti-Dsg1 antibodies of IgG4 subclass and IgG4/IgG1 ratio（r = 0.527, 0.565, respectively, both P < 0.01）. Conclusions Breg cells are mainly associated with the production of antibodies in and disease severity of pemphigus, while the actual mechanism of action remains unknown.