生酮饮食对难治性癫痫患儿滤泡辅助性T细胞及B细胞的影响  

The mechanism of hypogammaglobuinemia caused by ketongenic diet

作　　者：周厚福[1] 李成荣[2] 廖建湘[2] 王国兵[2] 林素芳[2] 陈黎[2] 

机构地区：[1]遵义医学院珠海校区,519090 [2]深圳市儿童医院,518026

出　　处：《中华微生物学和免疫学杂志》2014年第11期817-824,共8页Chinese Journal of Microbiology and Immunology

基　　金：深圳市科技计划项目（201103147）

摘　　要：目的：探讨生酮饮食（ KD ）导致低丙种球蛋白血症的可能机制。方法难治性癫痫（ IP）患儿36例，正常同龄对照17例，分别于KD治疗前后直接取血备检。流式细胞术检测外周血滤泡辅助性T细胞（ Tfh）、各阶段B细胞比例，ELISA检测外周血IL-21浓度，实时荧光定量PCR检测外周血CD4＋T细胞雷帕霉素靶蛋白（ mTOR ）、Blimp-1、Bcl-6和IL-21 mRNA表达及测定CD19细胞mTOR mRNA表达。结果（1）IP患儿Tfh细胞数量在KD治疗后明显下降（P＜0．05），IP患儿治疗前Tfh细胞比例与正常对照组无明显差异（P＞0．05）。（2）IP患儿KD治疗后Tfh细胞转录因子Bcl-6表达显著下降（P＜0．05），抑制因子Blimp-1表达增高（P＜0．05）。（3）KD治疗后IP患儿IL-21血浓度呈下降趋势，CD4＋T细胞IL-21 mRNA表达显著下降（P＜0．05）。（4）KD治疗前后CD27－IgD＋B细胞无显著差异（P＞0．05），CD27＋IgD＋B细胞和CD27－IgD－B细胞呈下降趋势，CD27＋IgD－B细胞和CD27＋IgD－CD38highB细胞治疗后明显下降（P＜0．05），Tfh细胞比例与CD27＋IgD－转化后记忆B细胞和CD27＋IgD－CD38high浆细胞数量呈正相关（r分别为0．644和0．609，P＜0．05）。（5）IP患儿KD治疗后CD4＋T细胞mTOR mRNA表达显著下降（P＜0．05），mTOR表达与Tfh比例呈正相关（r＝0．691，P＜0．05），mTOR表达与CD27＋IgD－转化后记忆B细胞和CD27＋IgD－CD38high浆细胞数量呈正相关（r分别为0．715和0．650，P＜0．05）。结论 KD可通过抑制CD4＋T细胞及B细胞mTOR表达下调Tfh细胞数量及功能，抑制B细胞分化，这可能是少数患儿长期KD治疗导致低丙种球蛋白血症的原因之一。Objective To investigate the possible mechanism of hypogammaglobuinemia caused by ketongenic diet （KD）.Methods Thirty-six children with intractable epilepsy （IP） and seventeen age-matched healthy children were recruited in this study.The percentages of B cells at various stages of devel-opment and follicular helper T （ Tfh） cells were detected by flow cytometry.The plasma concentrations of IL-21 were determined by ELISA.Real-time quantitative PCR was performed to detect the expression of mam-malian target of rapamycin （ mTOR） , Blimp-1, Bcl-6 and IL-21 at mRNA level in CD4＋T cells.Results mTOR at mRNA level was significantly down-regulated after KD treatment （P〈0.05）.The numbers of Tfh cells were positively correlated with the transcriptional level of mTOR （r=-0.691, P〈0.05）.Conclusion KD treatment might down-regulate Tfh and B cells through suppressing the expression of mTOR at mRNA level, suggesting a possible mechanism of hypogammaglobuinemia induced by KD treatment.

关 键 词：生酮饮食 雷帕霉素靶蛋白 B细胞 滤泡辅助性T细胞 IL-21 BCL-6 BLIMP-1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]