ICAR 2016:滤泡辅助性T细胞或能阻断乙肝病毒母婴传播

2018-07-13 编辑:略晓薛 来源:一诺医学 作者:ailanboman714
 
慢性乙型肝炎病毒(CHBV)感染是导致肝脏疾病进展的主要原因。而母婴传播是CHBV感染的主要原因。研究已表明滤泡调节性T细胞(TFH)能够通过激活B细胞调节体液免疫发挥抗HBV感染的作用。来自印度的研究人员在加利福尼亚州拉由拉市举办的2016第29届国际抗病毒研究大会(ICAR)上发表了一项滤泡调节性祖细胞阻止乙型肝炎病毒母婴传播的研究报道。
 
研究人员通过随访乙肝病毒表面抗原阳性(HBsAg+)妊娠妇女直到分娩,同时监测婴儿感染病毒的证据即HBsAg和HBV DNA。根据检测结果将受试者分HBV垂直传播组(N=2,GrpA)和非传播组(N=28,GrpB),通过流式细胞术检测TFH的表型及功能,同时检测亚群和共刺激分子(ICOS)。ELISA检测IL-21,通过NGS RNA检测两组PBMCs。RNA测序和流式细胞术所得数据通过qRTPCR再次检测确定。分析TFH和HBV DNA的相关性。通过多变量回归及ROC曲线分析该细胞及相关因子对HBV垂直传播的预测价值。
 
研究结果显示,CD4+CXCR5+(TFH)细胞频数在两组中均明显减少Grp(6.3+4.4% vs. 17.2+5%, p=0.001),同时TFH中ICOS的表达在GrpA中下降。RNA测序表明GrpA 组中TFH相关表型及转录因子的表达下降大于2倍与GrpB相比,比如CD4, BCL6, ICOS, SLAMF1,CXCR5 , BAFF,BATF,CD40, BAFFR 。aRT-PCR显示GrpA组中的IL-21也减少。TFH与HBV DNA有负相关关系。ROC曲线表明TFH对预测HBV垂直传播具有重要意义,cutoff值为9.5,同时具有高度特异性及灵敏度。
 
研究认为,TFH细胞能够作为预测HBV垂直传播的指标。而TFH细胞减少及功能失调可能说明病毒的垂直传播。
 
 
 
英文原文
 
Mother T Follicular Helper Cells Prevent Vertical Transmission of Hepatitis B to Their Babies
 
Nirupma Trehanpati, Ph.D., Ashish Vyas, M.S., paul David, M.S., Shiv Sarin, M.D., Nirupma Trehanpati, Ph.D.
 
Institute of Liver and Biliary Sciences, New Delhi, New Delhi, India
 
Chronic Hepatitis B infection (CHBV) is a leading cause of advanced liver diseases. Mother to child transmission accounts for most cases of CHBV infections. Follicular T helper cells (TFH) have shown a preventive role against HBV through activating the B cell mediated humoral immunity in patients.
 
METHODS: HBsAg+ pregnant mothers were followed up till delivery & babies were tested for evidence of HBV transmission(HBsAg or HBVDNA).Phenotyping and functionality of TFH cells and its subsets along with co-stimulatory molecule ICOS was performed by flowcytometry in transmitting (N=2,GrpA) & non transmitting mothers(N=28,GrpB). IL-21 was measured by ELISA. NGS RNA sequencing was done in PBMCs in both groups. RNA sequencing & FACS data was validated by qRTPCR. Correlation of TFH with HBV DNA was done. Multivariate regression & ROC was drawn to determine cellular predictors of HBV transmission.
 
RESULTS: CD4+CXCR5+(TFH) cells were significantly decreased in GrpA compared to GrpB(6.3+4.4% vs. 17.2+5%, p=0.001) and ICOS expression on TFH was also decreased in GrpA. RNA sequencing data also showed >2 fold decreased expression of TFH cell related genes likeCD4, BCL6, ICOS, SLAMF1,CXCR5 and BAFF,BATF,CD40, BAFFR in GrpA than GrpB. qRT-PCR showed IL-21 was also decreased in GrpA . Reciprocal relation was found between TFH cells and HBV DNA. ROC showed significance of TFH cells with cutoff 9.5 values for prediction of HBV transmission with highest specificity & sensitivity.
 
CONCLUSIONS: TFH cells can be used as a marker to predict HBV Transmission. Decreased and dysfunctional TFH cells inHBV infected may lead to vertical transmission.




本网站所有注明“来源:一诺医学”的文字、图片及音视频资料,版权均归一诺医学所有,其他平台转载需得到授权且注明:“来源:一诺医学”。本站所有转载文章系出于传递更多信息之目的,且明确注明来源和/或作者,不希望被转载的媒体和/或个人请与我们联系(0571-86635366),我们将立即进行删除处理。所有文章仅代表作者观点,不代表本站立场。

相关文章