丙酮酸脱氢酶复合物E2亚单位重组蛋白体外刺激PBC患者PBMCs实验研究

Peripheral blood T cell responses to recombinant PDC-E2 in primary biliary cirrhosis

目的:初步探讨丙酮酸脱氢酶复合物的E2亚单位(PDCE2)与原发性胆汁性肝硬化(PBC)发病机制间的关系.方法:用纯化的PDCE2重组蛋白体外刺激PBC患者外周血单个核细胞(PBMCs);3HTdR掺入法检测PBMCs增殖情况;ELASA法检测细胞上清中TNFα含量.结果:11例M2抗体阳性和1例AMA阳性的PBC患者中有8例出现不同程度PBMCs增殖,而2例AMA和M2抗体均阴性的PBC患者和4例AIH患者PBMCs均无增殖.11例M2抗体阳性的PBC患者刺激后TNFα分泌均明显增加.结论:PBC患者外周血中存在针对PDCE2的自身反应性T细胞;TNFα可能在PBC的病理损伤中发挥重要作用.

AIM: To evaluate the peripheral blood T cell responses to PDC-E2 and its possible role in the pathogenesis of primary biliary cirrhosis (PBC). METHODS: Fourteen patients with PBC and four patients with autoimmune hepatitis (AIH) were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) were stimulated by purified recombinant PDC-E2. Stimulation index was measured by ~3H-TdR incorporation assay and TNF-a was detected in the supernatant of culture by ELISA. RESULTS: The proliferation of PBMCs was observed in 8 out of the 14 PBC patients, who were antimitochomdrial antibody (AMA) or anti-M2 positive. AMA positivity or anti-M2 positivity was not observed in AIH patients. TNF-a secretion increased significantly after stimulation in all the 11 anti-M2 positive PBC patients. CONCLUSION: The results suggest the possibility of using PDC-E2 as a target antigen to induce autoimmune damage in PBC and that TNF-a may play an important role in this damage.