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使用OKT3单克隆抗体成功逆转急性心脏移植排斥反应。

Successful reversal of acute cardiac allograft rejection with OKT*3 monoclonal antibody.

作者信息

Costanzo-Nordin M R, Silver M A, O'Connell J B, Pifarre R, Grady K L, Winters G L, Murdock D K, Sullivan H J, Grieco J G, Scanlon P J

机构信息

Department of Medicine, Loyola University Medical Center, Maywood, IL 60153.

出版信息

Circulation. 1987 Nov;76(5 Pt 2):V71-80.

PMID:3311459
Abstract

The efficacy of OKT3 monoclonal antibody in reversing acute cardiac allograft rejection was investigated in 10 cardiac transplant recipients aged 5 to 57 years (mean 34 +/- 18) and treated with the same induction and maintenance immunosuppression. Serial endomyocardial biopsies, right heart catheterization, and echocardiograms were performed for rejection surveillance. After intensified immunosuppression with equine antithymocyte globulins and steroids, nine patients showed persistent rejection (lymphocytic infiltration and myocyte necrosis). Conventional immunosuppression was contraindicated in one patient. OKT3 (5 mg by intravenous push daily for 14 days) resulted in complete resolution of rejection in nine of 10 patients (90%). After therapy with OKT3 mean right atrial and pulmonary arterial wedge pressure were significantly lower (9.1 +/- 4.0 vs 4.8 +/- 2.0 mm Hg and 13.4 +/- 4.3 vs 8.0 +/- 3.3 mm Hg, respectively; p less than .05). Cardiac index was doubled in two patients with rejection-induced cardiac dysfunction (1.5 vs 3.2 and 1.6 vs 2.7 liters/min/m2). Only two patients developed antibodies to OKT3. Fever, nausea and headache occurred with the first three doses of OKT3 and did not recur. One patient developed aseptic meningitis. OKT3 effectively reverses refractory cardiac allograft rejection before the development of irreversible graft dysfunction. Patients who do not develop antibodies to OKT3 can be retreated with this drug. Adverse reactions to OKT3 are self-limited.

摘要

在10名年龄为5至57岁(平均34±18岁)且接受相同诱导和维持免疫抑制治疗的心脏移植受者中,研究了OKT3单克隆抗体逆转急性心脏移植排斥反应的疗效。进行了系列心内膜心肌活检、右心导管检查和超声心动图以监测排斥反应。在用马抗胸腺细胞球蛋白和类固醇强化免疫抑制后,9名患者出现持续性排斥反应(淋巴细胞浸润和心肌细胞坏死)。1名患者禁忌常规免疫抑制。OKT3(每日静脉推注5毫克,共14天)使10名患者中的9名(90%)排斥反应完全消退。用OKT3治疗后,平均右心房压和肺动脉楔压显著降低(分别为9.1±4.0对4.8±2.0毫米汞柱和13.4±4.3对8.0±3.3毫米汞柱;p<0.05)。两名因排斥反应导致心脏功能障碍的患者心脏指数翻倍(分别为1.5对3.2和1.6对2.7升/分钟/平方米)。只有两名患者产生了针对OKT3的抗体。发热、恶心和头痛在OKT3的前三剂给药时出现,且未再次发生。1名患者发生了无菌性脑膜炎。OKT3在不可逆移植功能障碍发生之前有效地逆转难治性心脏移植排斥反应。未产生针对OKT3抗体的患者可用该药再次治疗。OKT3的不良反应是自限性的。

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