Liu Yong, Zhao Pingwei, Qu Zhihui, Ayana Desalegn Admassu, Jiang Yanfang
Key Laboratory of Zoonosis Research, Ministry of Education, The First Hospital of Jilin University, Changchun, 130032, China.
Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, China.
Int Immunopharmacol. 2014 Sep;22(1):98-106. doi: 10.1016/j.intimp.2014.06.024. Epub 2014 Jun 24.
The frequency of different subsets of CD4(+)CXCR5(+) TFH cells and serum cytokine levels were analyzed in a total of 14 patients with newly diagnosed hepatitis B virus-associated membranous nephropathy (HBV-MN), 12 individuals with immune-tolerant HBV infection (HBV-IT) and 12 healthy controls (HC). Serum cytokine levels were measured before and 10-12 weeks after treatment. Significantly higher frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, and higher serum levels of IL-17A, IFN-γ, IL-2, IL-10, IL-4 and IL-21 were detected in HBV-MN patients compared to the HC. The percentage of CD4(+)CXCR5(+) TFH cells and serum IL-21 level in HBV-MN patients were also higher than the HBV-IT. The percentage of CD4(+)CXCR5(+) TFH cell was negatively correlated with the value of eGFR, and the percentage of CD4(+)CXCR5(+)ICOS(+) TFH cells was positively correlated with the 24-h urinary protein concentration. Notably, the percentage of CD4(+)CXCR5(+)PD-1(+) TFH cells was positively correlated with serum IL-21 level and 24-h urinary protein concentration. Treatment with prednisone or/and immunosuppressive drugs significantly reduced the frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+) TFH cells and serum IL-21 level, but increased IL-4 and IL-10 levels in the patients. CD4(+)CXCR5(+) TFH cells, especially CD4(+)CXCR5(+)PD-1(+) TFH cells may participate in the pathogenesis of HBV-MN.
共对14例新诊断的乙型肝炎病毒相关性膜性肾病（HBV-MN）患者、12例免疫耐受的HBV感染（HBV-IT）个体和12名健康对照者（HC）分析了CD4(+)CXCR5(+) TFH细胞不同亚群的频率和血清细胞因子水平。在治疗前及治疗10 - 12周后测量血清细胞因子水平。与HC相比，HBV-MN患者中CD4(+)CXCR5(+)、CD4(+)CXCR5(+)ICOS(+)和CD4(+)CXCR5(+)PD-1(+) TFH细胞的频率显著更高，且血清IL-17A、IFN-γ、IL-2、IL-10、IL-4和IL-21水平更高。HBV-MN患者中CD4(+)CXCR5(+) TFH细胞百分比和血清IL-21水平也高于HBV-IT患者。CD4(+)CXCR5(+) TFH细胞百分比与估算肾小球滤过率（eGFR）值呈负相关，CD4(+)CXCR5(+)ICOS(+) TFH细胞百分比与24小时尿蛋白浓度呈正相关。值得注意的是，CD4(+)CXCR5(+)PD-1(+) TFH细胞百分比与血清IL-21水平和24小时尿蛋白浓度呈正相关。泼尼松或/和免疫抑制药物治疗显著降低了患者中CD4(+)CXCR5(+)、CD4(+)CXCR5(+)PD-1(+) TFH细胞的频率和血清IL-21水平，但增加了IL-4和IL-10水平。CD4(+)CXCR5(+) TFH细胞，尤其是CD4(+)CXCR5(+)PD-1(+) TFH细胞可能参与了HBV-MN的发病机制。
