Pretagostini R, Berloco P, Poli L, Cinti P, Di Nicuolo A, De Simone P, Colonnello M, Salerno A, Alfani D, Cortesini R
2nd Surgical Clinic, La Sapienza University of Rome, Italy.
ASAIO J. 1996 Sep-Oct;42(5):M645-8. doi: 10.1097/00002480-199609000-00067.
The presence of alloantibodies may play a role in accelerated or acute humoral rejection. Different therapeutic strategies based on a removal of anti donor antibodies and prevention of their resynthesis have been used in the management of transplant rejection episodes. Immunoadsorption with staphylococcal protein A, a method to selectively remove immunoglobulin G, may represent a new treatment to reverse humoral rejection in kidney transplantation. From 1991 to January 1996, such a method was used in 23 patients in whom an acute humoral rejection developed over a mean period of 14.1 +/- 9.5 days after operation. Twenty-two patients had been transplanted from living donors and one from a cadaveric donor. The ages ranged from 23 to 58 years (mean, 34 +/- 10 years). All transplants were performed according to a negative direct crossmatch. Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). Rejection was diagnosed on the basis of hematochemical tests, Doppler ultrasonography, and kidney biopsy. Only steroid and monoclonal and polyclonal antibody resistant rejections with > 165% positive direct crossmatches against the donor were treated with Protein A immunoabsorption. The procedure used is based on the treatment of 2-3 plasma volumes for the first 2 days and then every other day until a negative crossmatch is obtained, together with improvement in clinical status (mean treatments, 7.3 +/- 4.5 [range, 4-23]; mean duration of treatment, 12.3 +/- 10.2 days [range, 3-44]). From the start of treatment, azathioprine is replaced by cyclophosphamide at a dose of 1-2 mg/kg/day. During treatment, a remarkable fall in immunoglobulin G levels is achieved on the first day, whereas immunoglobulin M titers remain constant, with a slight decrease in serum albumin. Immediately after treatment, a negative crossmatch was found in 22 (95.6%) of 23 patients. In six patients (26%), graft function did not recover, and one patient (4.3%) died. Preliminary results show that immunoabsorption with staphylococcal protein A may be an effective support in the treatment of humoral acute rejection, particularly when it is performed as soon as an early diagnosis of humoral rejection is made. In fact, such treatment has a highly selective adsorption, allows treatment of large volumes of plasma, and can achieve a rapid decrease in the titer of circulating immunoglobulins.
同种抗体的存在可能在加速性或急性体液排斥反应中起作用。基于去除抗供体抗体并防止其重新合成的不同治疗策略已被用于处理移植排斥反应。用葡萄球菌蛋白A进行免疫吸附，一种选择性去除免疫球蛋白G的方法，可能代表了一种逆转肾移植中体液排斥反应的新疗法。从1991年到1996年1月，该方法用于23例患者，这些患者在术后平均14.1±9.5天发生急性体液排斥反应。22例患者接受活体供体移植，1例接受尸体供体移植。年龄范围为23至58岁（平均34±10岁）。所有移植均根据阴性直接交叉配型进行。基础免疫抑制包括环孢素、类固醇、硫唑嘌呤以及抗淋巴细胞球蛋白或单克隆抗体（OKT3）。根据血液化学检查、多普勒超声和肾活检诊断排斥反应。仅对针对供体直接交叉配型阳性率>165%的对类固醇、单克隆和多克隆抗体耐药的排斥反应采用蛋白A免疫吸附治疗。所采用的程序是在开始的2天内处理2 - 3个血浆容量，然后每隔一天处理一次，直到获得阴性交叉配型，同时临床状况改善（平均治疗次数，7.3±4.5[范围，4 - 23]；平均治疗持续时间，12.3±10.2天[范围，3 - 44]）。从治疗开始，硫唑嘌呤被剂量为1 - 2mg/kg/天的环磷酰胺替代。治疗期间，第一天免疫球蛋白G水平显著下降，而免疫球蛋白M滴度保持不变，血清白蛋白略有下降。治疗后立即在23例患者中的22例（95.6%）发现阴性交叉配型。6例患者（26%）移植肾功能未恢复，1例患者（4.3%）死亡。初步结果表明，用葡萄球菌蛋白A进行免疫吸附可能是治疗体液性急性排斥反应的有效支持手段，特别是在早期诊断体液性排斥反应后尽快进行时。事实上，这种治疗具有高度选择性吸附，允许处理大量血浆，并能使循环免疫球蛋白滴度迅速下降。
