Data_Sheet_1_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.docx

Background: 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.
Methods: 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.
Results: During a median follow-up of 7.4 years, allograft survival was significantly lower in DSA-positive as compared to DSA-negative patients (p < 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.
Conclusion: 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.

背景：目前尚不完全明确，为何部分携带预存供体特异性抗HLA抗体（preformed donor-specific anti-HLA antibodies, DSA）的肾移植受者会因抗体介导排斥反应（antibody-mediated rejection, ABMR）出现移植肾存活率下降，而多数DSA阳性受者却能获得良好的长期预后。可溶性CD30（soluble CD30, sCD30）水平升高已被证实是一项颇具潜力的生物标志物，可提示免疫高危人群中与DSA协同存在的有害T细胞辅助作用。本研究假设，这一关联在中危人群中同样成立。
方法：本研究回顾性分析了287例CDC交叉配型阴性的肾移植受者的术前血清样本，这些受者均接受巴利昔单抗诱导治疗及以他克莫司为基础的维持治疗，检测其样本中DSA与sCD30的表达情况。依据Banff 2019分类标准确定ABMR的发生率，并统计死亡删失移植肾存活率。
结果：中位随访7.4年期间，DSA阳性受者的移植肾存活率显著低于DSA阴性受者（p<0.001）。在DSA阳性受者中，尤以强阳性DSA（平均荧光强度Mean Fluorescence Intensity, MFI>5000）受者最为显著：与sCD30水平较低的受者相比，sCD30水平升高者的移植肾失功进展更快，其3年移植肾存活率分别为75%与95%。但无论sCD30状态如何，DSA阳性受者的长期存活率均无显著差异。同样，在携带DSA的受者中，sCD30阳性与sCD30阴性者的早期ABMR发生率及病变评分特征均无明显差异。此外，sCD30水平升高无法预测DSA的早期持续存在。
结论：在中危肾移植受者中，预存DSA与ABMR发生风险升高及长期移植肾失功风险升高相关，且这一关联不受sCD30水平的影响。