肾移植受者血清抗体IgG1及IgG3亚型介导对凋亡细胞的反应性并激活补体途径

Serum IgG1 and IgG3 subclass antibodies in kidney transplant recipients dominate the reactivity to apoptotic cells and activate complement pathway

目的检测肾移植受者术前血清内多反应性IgG抗体亚型与凋亡细胞的反应性及与补体激活途径的关系,初步探讨此类抗体导致移植肾排异反应及影响移植肾存活的机制。方法选取50例肾移植患者术前血清学标本,应用流式细胞技术检测血清内IgG抗体亚型(IgG1-IgG4)对凋亡细胞的反应性,并检测此类抗体与凋亡细胞反应后,能否激活补体途径,导致C4d沉积于靶细胞表面,并分析IgG亚型对凋亡细胞反应强度与C4d在靶细胞表面沉积强度的相关性。结果肾移植患者血清内IgG抗体对凋亡细胞的反应性主要由IgG1及IgG3亚型介导,而极少患者的血清由IgG2或IgG4介导对凋亡细胞的反应,IgG1及IgG3亚型对凋亡细胞的反应性与C4d在靶细胞表面沉积强度呈显著相关性(P<0.001,P=0.005)。结论本研究初步揭示肾移植患者血清内多反应性IgG抗体通过IgG1及IgG3亚型介导对凋亡细胞的反应性,并可能通过激活补体途径造成移植肾损伤。

Objective To investigate the association between reactivity of IgG subclass in kidney transplant recipients to apoptotic cells and complement activation and explore the mechanism of effect of polyreactiveIgG on kidney allograft rejection and graft loss.Methods Pre-transplant serum samples were selected form 50 kidney transplant recipients.Reactivity of IgG subclass to apoptotic cells was detected using flow cytometry.We also observed whether polyreactive IgG could activate complement pathway,leading C4 ddeposition on target cells after binding to apoptotic cells.The association between reactivity of IgG subclass to apoptotic cells and C4 ddeposition on target cells was analyzed.Results Our studies showed that IgG reactivity to apoptotic cells was almost exclusively mediated by IgG1 and IgG3subclasses.Few samples showed IgG2 or IgG4reactivity to apoptotic cells.Moreover,we observed a strong association between IgG1 and IgG3reactivity to apoptotic cells and C4 ddeposition on target cells（P〈0.001,P=0.005）.Conclusion Our studies preliminarily revealed that reactivity of polyreactive IgG in kidney transplant recipients to apoptotic cells was mediated by IgG1 and IgG3subclasses,they lead to kidney allograft injury probably through activation of complement pathway.