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首页> 美国卫生研究院文献>Lippincott Williams Wilkins Open Access >The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients
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The Influence of Immunosuppressive Agents on the Risk of De Novo Donor-Specific HLA Antibody Production in Solid Organ Transplant Recipients

机译：免疫抑制剂对固体器官移植受者从头供体特异性HLA抗体生产风险的影响

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摘要

Production of de novo donor-specific antibodies (dnDSA) is a major risk factor for acute and chronic antibody-mediated rejection and graft loss after all solid organ transplantation. In this article, we review the data available on the risk of individual immunosuppressive agents and their ability to prevent dnDSA production. Induction therapy with rabbit antithymocyte globulin may achieve a short-term decrease in dnDSA production in moderately sensitized patients. Rituximab induction may be beneficial in sensitized patients, and in abrogating rebound antibody response in patients undergoing desensitization or treatment for antibody-mediated rejection. Use of bortezomib for induction therapy in at-risk patients is of interest, but the benefits are unproven. In maintenance regimens, nonadherent and previously sensitized patients are not suitable for aggressive weaning protocols, particularly early calcineurin inhibitor withdrawal without lymphocyte-depleting induction. Early conversion to mammalian target of rapamycin inhibitor monotherapy has been reported to increase the risk of dnDSA formation, but a combination of mammalian target of rapamycin inhibitor and reduced-exposure calcineurin inhibitor does not appear to alter the risk. Early steroid therapy withdrawal in standard-risk patients after induction has no known dnDSA penalty. The available data do not demonstrate a consistent effect of mycophenolic acid on dnDSA production. Risk minimization for dnDSA requires monitoring of adherence, appropriate risk stratification, risk-based immunosuppression intensity, and prospective DSA surveillance.
机译：从头产生供体特异性抗体（dnDSA）是所有实体器官移植后急性和慢性抗体介导的排斥和移植物丢失的主要危险因素。在本文中，我们回顾了有关单个免疫抑制剂的风险及其预防dnDSA产生的能力的可用数据。兔抗胸腺细胞球蛋白的诱导疗法可在中度敏感患者中实现dnDSA产生的短期减少。利妥昔单抗的诱导可能对致敏的患者有益，并且在接受脱敏或抗体介导的排斥反应治疗的患者中废除反弹抗体应答。在危险患者中使用硼替佐米进行诱导治疗是令人感兴趣的，但是其益处尚未得到证实。在维持治疗方案中，非依从性且先前致敏的患者不适合积极的断奶方案，尤其是早期钙调神经磷酸酶抑制剂的撤药而无淋巴细胞衰竭。据报道，将雷帕霉素抑制剂单药早期转化为哺乳动物靶标会增加dnDSA形成的风险，但将雷帕霉素抑制剂与减少暴露量的钙调神经磷酸酶抑制剂的哺乳动物靶标联合使用似乎不会改变该风险。标准风险高的患者在诱导后早期停用类固醇激素疗法尚无已知的dnDSA罚款。现有数据不能证明麦考酚酸对dnDSA的生产产生一致的影响。最小化dnDSA的风险需要监控依从性，适当的风险分层，基于风险的免疫抑制强度以及前瞻性DSA监视。

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