Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action
Posttransplant therapy using high-dose human immunoglobulin (intravenous gammaglobulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action
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DOI：
10.1097/00007890-199809270-00017
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发表时间：
1998-09-27
期刊：
影响因子：
6.2
通讯作者：
Tyan, DB
中科院分区：
文献类型：
--
作者：
Jordan, SC;Quartel, AW;Tyan, DB
背景静脉注射丙种球蛋白（MG）含有抗独特型抗体，在体外和体内是HLA特异性同种抗体的有效抑制剂。此外，高度HLA同种异体致敏的等待移植的患者可以通过MG输注显著降低HLA同种异体抗体水平，并且随后的移植可以成功地用交叉配型阴性的组织不相容的器官完成。在这项研究中，我们研究了可能使用MG来减少移植后产生的供体特异性抗HLA同种异体抗体及其在治疗抗体介导的同种异体移植排斥反应（AR）事件中的疗效。我们提供了10例严重同种异体移植排斥反应患者的数据，其中4例发生了与高水平的供者特异性抗HLA同种异体抗体相关的AR事件。大多数患者显示AR发作迅速改善，所有患者在IVIG输注后2-5天内消退。IVIG治疗也迅速降低IVIG输注后供体特异性抗HLA同种抗体水平。所有AR发作均逆转。10例患者中有9例无复发性排斥反应，有些患者随访长达5年。两名患者的蛋白G柱分离研究结果表明，IVIG诱导体内抑制的潜在机制是一系列事件，从最初的抑制（由于IgG的被动转移）到最终的IgM或IgG封闭抗体的主动诱导。MG似乎是一种有效的治疗方法，可以控制心脏和肾脏移植受者的移植后AR发作，包括常规治疗无效的患者。与供体特异性细胞毒性抗体相关的血管排斥反应似乎对MG治疗特别敏感。
Background. Intravenous gammaglobulin (MG) contains anti-idiotypic antibodies that are potent inhibitors of HLA-specific alloantibodies in vitro and in vivo. In addition, highly HLA-allosensitized patients awaiting transplantation can have HLA alloantibody levels reduced dramatically by MG infusions, and subsequent transplantation can be accomplished successfully with a crossmatch-negative, histoincompatible organ.Methods. In this study, we investigated the possible use of MG to reduce donor-specific anti-HLA alloantibodies arising after transplantation and its efficacy in treating antibody-mediated allograft rejection (AR) episodes. We present data on 10 patients with severe allograft rejection, four of whom developed AR episodes associated with high levels of donor-specific anti-HLA alloantibodies.Results. Most patients showed rapid improvements in AR episodes, with resolution noted within 2-5 days after IVIG infusions in all patients. IVIG treatment also rapidly reduced donor-specific anti-HLA alloantibody levels after IVIG infusion. All AR episodes were reversed. Freedom from recurrent rejection episodes was seen in 9 of 10 patients, some with up to 5 years of follow-up. Results of protein G column fractionation studies from two patients suggest that the potential mechanism by which IVIG induces in vivo suppression is a sequence of events leading from initial inhibition due to passive transfer of IgG to eventual active induction of an IgM or IgG blocking antibody in the recipient.Conclusion. MG appears to be an effective therapy to control posttransplant AR episodes in heart and kidney transplant recipients, including patients who have had no success with conventional therapies. Vascular rejection episodes associated with development of donor-specific cytotoxic antibodies appears to be particularly responsive to MG therapy.