Yuling He, Ruijing Xiao, Xiang Ji, Yanping Jiang, Lang Chen, Li Li, Dingping Yang, Xinti Tan, Jingyi Liu, Zhiqing Tang, Yongyi Bi, Bing Xia, Xinxing Wu, Youxin Jin, Fox David A, Lundy Steven K, Guohua Ding, Jinquan Tan
Department of Immunology, Wuhan University School of Medicine, Wuhan University, Dong Hu Road 115, 430071 Wuchang, Wuhan, P.R. China.
J Am Soc Nephrol. 2008 Nov;19(11):2130-9. doi: 10.1681/ASN.2007121303. Epub 2008 Jul 23.
The source of IgA and the mechanism for deposition of IgA in the mesangium remain unknown for primary IgA nephropathy. Because CD19(+)CD5(+) B cells are important producers of IgA and contribute to several autoimmune diseases, they may play an important role in IgA nephropathy. In this study, flow cytometry, quantitative PCR, and confocal microscopy were used to assess the frequency, distribution, Ig production, CD phenotypes, cytokine production, and sensitivity to apoptosis of CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies of 36 patients with primary IgA nephropathy. All patients with IgA nephropathy were significantly more likely to have CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney biopsies than were five control subjects and 10 patients with active systemic lupus erythematosus. The 33 patients who had IgA nephropathy and responded to treatment demonstrated a significant decrease in CD19(+)CD5(+) B cells in the peripheral blood, peritoneal fluid, and kidney (all P < 0.01). In the three patients who had IgA nephropathy and did not respond to treatment, the frequency of CD19(+)CD5(+) B cells did not change. CD19(+)CD5(+) B cells isolated from patients with untreated IgA nephropathy expressed higher levels of IgA, produced more IFN-gamma, and were more resistant to CD95L-induced apoptosis than cells isolated from control subjects and patients with lupus; these properties reversed with effective treatment of IgA nephropathy. In conclusion, these results strongly suggest that CD19(+)CD5(+) B cells play a prominent role in the pathogenesis of primary IgA nephropathy.
原发性IgA肾病中IgA的来源以及IgA在系膜中沉积的机制尚不清楚。由于CD19(+)CD5(+) B细胞是IgA的重要产生者，并与多种自身免疫性疾病有关，它们可能在IgA肾病中发挥重要作用。在本研究中，运用流式细胞术、定量PCR和共聚焦显微镜，对36例原发性IgA肾病患者外周血、腹腔积液和肾活检组织中CD19(+)CD5(+) B细胞的频率、分布、Ig产生、CD表型、细胞因子产生及对凋亡的敏感性进行评估。与5名对照受试者和10例活动性系统性红斑狼疮患者相比，所有IgA肾病患者外周血、腹腔积液和肾活检组织中更易出现CD19(+)CD5(+) B细胞。33例对治疗有反应的IgA肾病患者外周血、腹腔积液和肾组织中的CD19(+)CD5(+) B细胞显著减少（均P < 0.01）。3例对治疗无反应的IgA肾病患者，其CD19(+)CD5(+) B细胞频率未发生变化。从未经治疗的IgA肾病患者分离出的CD19(+)CD5(+) B细胞比从对照受试者和狼疮患者分离出的细胞表达更高水平的IgA，产生更多的IFN-γ，且对CD95L诱导的凋亡更具抗性；这些特性在IgA肾病有效治疗后逆转。总之，这些结果强烈提示CD19(+)CD5(+) B细胞在原发性IgA肾病发病机制中起重要作用。
