重组人β2糖蛋白1作为抗磷脂抗体综合征口服耐受原的实验研究

Experimental studies of recombinant human β2-glycoprotein-1 as oral tolerogen in antiphospholipid antibody syndrome

目的:探讨口服重组人β2糖蛋白1(rhβ2-GP-1)诱导小鼠β2-GP-1特异性免疫耐受机制。方法:以rhβ2-GP-1免疫小鼠,在免疫的不同时间给予小鼠口服不同剂量的rhβ2-GP-1,应用3H-TdR掺入法检测免疫小鼠T淋巴细胞增殖水平,应用ELISA方法检测免疫小鼠抗β2糖蛋白1抗体(anti-β2-GP-1)产生滴度以及免疫小鼠IL-4、IL-10、IL-2、IFN-γ、TGF-β等细胞因子的产生情况。结果:在免疫的不同时间、口服不同剂量的rhβ2-GP-1可不同程度地诱导免疫小鼠anti-β2-GP-1滴度下降;耐受小鼠T淋巴细胞增殖水平明显降低(P<0.01);IL-4、IL-10、TGF-β水平显著升高,IL-2水平显著降低,IFN-γ水平未见显著变化。结论:在合适的时间口服适当剂量的rhβ2-GP-1能够诱导小鼠β2-GP-1特异性免疫耐受。

Objective：To explore the mechanism of β-GP-1-specific immunologic tolerance of recombinant human β2-glycoprotein-1 （rhβ2-GP-1） as oral tolerogen in β2-glycoprotein-1 immunized mice. Methods： Mice were immunized with rhβ2-GP-1, and were administrated orally using hrβ2-GP-1 in different doses and periods. Levels of T lymphocyte proliferation were determined using 3 H-TdR incorporation method, titers of anti-β-glycoprotein-1 antibody and five cytokine concentrations in the tolerant mice were detected by ELISA. Results： Titers of anti-β2- glycoprotein-1 antibody in β2-GP-1-immunized mice induced by oral rhβ2-GP-1 were significantly decreased（ P 〈 0.01）. In tolerant mice, levels of T lymphocyte proliferation were decreased obviously（ P 〈 0.01 ）;concentrations of IL-4 ,IL-10, TGF-β were increased, and IL-2 was decreased. Conclusion：Oral administration of rhβ2-GP-1 in appropriate dose and suitable period could induce β2-GP-1-specific immunologic tolerance.