摘要
目的分析原发性胆汁性胆管炎(primary biliary cholangitis,PBC)患者腺苷代谢通路相关分子的变化及其与PBC炎性损伤的关系。方法连续选择2016年10月-2017年10月在太仓市第一人民医院和常熟市第二人民医院就诊的PBC患者49例和体检健康者36例。流式细胞术分析外周血腺苷代谢通路关键分子CD39和CD73在CD4+T细胞和Foxp3+调节性T细胞(Treg)中的表达情况,高效液相色谱串联质谱(UHPLC-Q-TOF/MS)分析患者血清三磷酸腺苷(ATP)水平。分析以上指标的统计学差异及其与肝脏炎性损伤指标丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、γ-谷氨酰基转移酶(GGT)、碱性磷酸酶(ALP)和Mayo评分之间的相关性。结果 PBC组CD4+CD39+T细胞占CD4+T细胞比例[(5.28±1.92)%]较对照组[(11.01±3.19)%]显著降低(t=10.25,P<0.01),CD4+CD25+Foxp3+CD39+T细胞(CD39+Treg)在Foxp3+Treg中所占比例[(23.75±9.48)%]同样显著低于对照组[(54.68±5.18)%],差异有统计学意义(t=13.79,P<0.01)。PBC组和对照组CD4+CD73+T细胞在CD4+T细胞中的占比和CD4+CD25+Foxp3+CD73+T细胞在Foxp3+Treg中的占比差异无统计学意义(t值分别为2.235和1.083,P>0.05)。PBC组血清ATP水平[(200.28±79.41)μg/L]明显高于对照组[(89.20±33.76)μg/L],差异有统计学意义(t=8.367,P<0.01)。PBC组CD39+Treg占Treg比例与ATP、GGT和Mayo评分水平呈负相关关系(r值分别为-0.413、-0.378和-0.382,P值分别为0.003、0.007和0.007)。结论 CD39+Treg在PBC患者中比例显著降低,可能通过降低ATP的分解导致炎性损伤加剧。CD73+Treg在PBC患者中未见明显变化。
Objective To evaluate the changes of adenosine metabolism pathway related molecules and their contribution to inflammatory injury in primary biliary cholangitis （PBC）. Methods The consecutive samples of 49 subjects with PBC from The First People＇s Hospital of Taicang and The Second People＇s Hospital of Changshu were recruited from October 2016 to October 2017, and 36 healthy controls were involved in this study. The expression of CD39 and CD73 on CD4 ＋ T cells and Foxp3 ＋ regulatory T cells were assayed by flow cytometry and the concentration of adenosine triphosphate （ATP） in serum was analyzed by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry （UHPLC-Q-TOF/MS）. The correlations between Tregs, ATP and liver function were analyzed, i. e. , alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, gamma-glutamyhransferase （GGT）, alkaline phosphatase （ALP） and Mayo scores. Results In the patients with PBC, low proportions of CD4 ＋ CD39 ＋ T cells were noted compared with healthy controls [ （5.28 ± 1.92） % vs (11. 01 ± 3.19） %, t = 10.25, P 〈 0. 01 ]. The patients with PBC also had significantly low proportion of CD4 ＋ CD25 ＋ Foxp3 ＋ CD39 ＋ T cells compared with healthy controls t (23.75 ± 9.48) % vs (54.68± 5.18） %, t = 13,79, P 〈0.01]. No significant difference of the proportion of CD4＋ CD73 ＋ T or CD4＋ CD25 ＋ Foxp3 ＋ CD39 ＋ T cells was found between PBC and control groups （t values were 2. 235 and 1. 083, P 〉 0.05）. The level of serum ATP was higher in the patients with PBC than that of healthy controls [ （200.28 ± 79.41) μg/L vs （89.20 ± 33.76） μg/L, t = 8. 367, P 〈 0.01 ]. A significant correlation was demonstrated between the proportion of CD39 ＋ Treg in total Treg cells and the levels of ATP (r =-0. 413, P = 0.003), GGT (r =-0. 378, P = 0. 007) and Mayo score (r =-0. 382, P = 0. 007). Conclusion The low proportion of CD39 ＋ Treg cells may contribute to the down-regulation of ATP hydrolysis in the patients with PBC. No significant change of CD73 ＋ Treg cells was found in PBC patients.
作者
李勇
王金湖
鞠少卿
仲人前
张悦梅
龚燕萍
曹季军
吕心路
潘晓园
蒋廷旺
LI Yong;WANG Jinhu;JU Shaoqing;ZHONG Renqian;ZHANG Yuemei;GONG Yanping;CAO Jijun;LYU Xinlu;PAN Xi- aoyuan;JIANG Tingwang(Department of Clinical Laboratory, The First People＇s Hospital of Taicang City, Taicang 215400, Jiangsu;Laboratory Diagnostic Center, Affiliated Hospital of Nantong University, Nantong 226000, Jiangsu;Department of Laboratory Diagnostics, Changzheng Hospital, Shanghai 200003;Institution of Laboratory Medicine of Changshu, Changshu 215500, Jiangsu, China)
出处
《临床检验杂志》
CAS
CSCD
2018年第4期248-252,共5页
Chinese Journal of Clinical Laboratory Science
基金
苏州市科教兴卫青年项目(kjxw2014046)
江苏省青年医学人才培养项目(QNRC2016214)
苏州市重大疾病
传染病预防和控制关键技术项目(GWZX201604)
常熟市卫计委科技计划项目(csws201609)
