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可溶性CD30水平升高对伴有预存供者特异性抗体的中度风险肾移植受者早期抗体介导性排斥反应的发生率及长期预后无影响。

Increased Levels of sCD30 Have No Impact on the Incidence of Early ABMR and Long-Term Outcome in Intermediate-Risk Renal Transplant Patients With Preformed DSA.

作者信息

Drasch Thomas, Bach Christian, Luber Markus, Spriewald Bernd, Utpatel Kirsten, Büttner-Herold Maike, Banas Bernhard, Zecher Daniel

机构信息

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.

出版信息

Front Med (Lausanne). 2021 Nov 8;8:778864. doi: 10.3389/fmed.2021.778864. eCollection 2021.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e5e/8606593/9cb1c9c9e454/fmed-08-778864-g0001.jpg

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