Drasch Thomas, Bach Christian, Luber Markus, Spriewald Bernd, Utpatel Kirsten, Büttner-Herold Maike, Banas Bernhard, Zecher Daniel
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Department of Internal Medicine 5-Hematology and Oncology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
Front Med (Lausanne). 2021 Nov 8;8:778864. doi: 10.3389/fmed.2021.778864. eCollection 2021.
It is still incompletely understood why some patients with preformed donor-specific anti-HLA antibodies (DSA) have reduced kidney allograft survival secondary to antibody-mediated rejection (ABMR), whereas many DSA-positive patients have favorable long-term outcomes. Elevated levels of soluble CD30 (sCD30) have emerged as a promising biomarker indicating deleterious T-cell help in conjunction with DSA in immunologically high-risk patients. We hypothesized that this would also be true in intermediate-risk patients. We retrospectively analyzed pre-transplant sera from 287 CDC-crossmatch negative patients treated with basiliximab induction and tacrolimus-based maintenance therapy for the presence of DSA and sCD30. The incidence of ABMR according to the Banff 2019 classification and death-censored allograft survival were determined. During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients ( < 0.001). In DSA-positive patients, most pronounced in those with strong DSA (MFI > 5,000), increased levels of sCD30 were associated with accelerated graft loss compared to patients with low sCD30 (3-year allograft survival 75 vs. 95%). Long-term survival, however, was comparable in DSA-positive patients irrespective of sCD30 status. Likewise, the incidence of early ABMR and lesion score characteristics were comparable between sCD30-positive and sCD30-negative patients with DSA. Finally, increased sCD30 levels were not predictive for early persistence of DSA. Preformed DSA are associated with an increased risk for ABMR and long-term graft loss independent of sCD30 levels in intermediate-risk kidney transplant patients.
目前仍未完全理解为何一些预先存在供者特异性抗HLA抗体（DSA）的患者会因抗体介导的排斥反应（ABMR）而导致肾移植存活率降低，而许多DSA阳性患者却有良好的长期预后。可溶性CD30（sCD30）水平升高已成为一种有前景的生物标志物，表明在免疫高风险患者中，sCD30与DSA共同作用时存在有害的T细胞辅助。我们推测在中度风险患者中也是如此。我们回顾性分析了287例接受巴利昔单抗诱导和以他克莫司为基础的维持治疗的CDC交叉配型阴性患者的移植前血清，以检测DSA和sCD30的存在情况。根据2019年班夫分类确定ABMR的发生率以及死亡截尾的移植肾存活率。在中位随访7.4年期间，DSA阳性患者的移植肾存活率显著低于DSA阴性患者（<0.001）。在DSA阳性患者中，尤其是那些DSA强阳性（平均荧光强度>MFI>5000）的患者，与sCD30水平低的患者相比，sCD30水平升高与移植肾丢失加速相关（3年移植肾存活率分别为75%和95%）。然而，无论sCD30状态如何，DSA阳性患者的长期存活率相当。同样，DSA阳性的sCD30阳性和sCD30阴性患者之间早期ABMR的发生率和病变评分特征相当。最后，sCD30水平升高并不能预测DSA的早期持续存在。在中度风险的肾移植患者中，预先存在的DSA与ABMR风险增加和长期移植肾丢失相关，且与sCD30水平无关。
