Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory on Organ Donation and Transplant Immunology, Guangzhou, China.
Front Immunol. 2022 Apr 13;13:869444. doi: 10.3389/fimmu.2022.869444. eCollection 2022.
B cell-activating factor (BAFF), which is critical in the activation and differentiation of B cells, is a candidate diagnostic and predictive biomarker for antibody-mediated rejection (ABMR). We aimed to investigate the value of serum soluble BAFF (sBAFF) for the diagnosis and risk stratification of ABMR after kidney transplantation.
In the diagnostic study, sBAFF level among ABMR (n = 25), T cell-mediated rejection (TCMR) (n = 14), 4 other pathological lesions (n = 21), and stable allograft function group (n = 15) were compared. In the nested case-control study, kidney allograft recipients with donor-specific antibody (DSA) or ABMR (n = 16) vs. stable allograft function (n = 7) were enrolled, and sBAFF was measured preoperatively, at D7, M1, M3, M6, M9, M12, M18 posttransplant and at allograft biopsy.
There was no significant difference in sBAFF level at biopsy between ABMR and non-ABMR groups. Longitudinal study showed that the sBAFF levels decreased dramatically at D7 in both groups. The sBAFF level in the DSA group started to increase within M1, while in the stable group, it maintained a low level until M3 and M6. The sBAFF levels of the DSA group were significantly higher than that of the stable group at M1 [1,013.23 (633.97, 1,277.38) pg/ml vs. 462.69 (438.77, 586.48) pg/ml, = 0.005], M3 [1,472.07 (912.79, 1,922.08) pg/ml vs. 561.63 (489.77, 630.00) pg/ml, = 0.002], and M6 [1,217.95 (965.25, 1,321.43) pg/ml vs. 726.93 (604.77, 924.60) pg/ml, = 0.027]. sBAFF levels at M3 had the best predictive value for the DSA/ABMR with the area under the receiver operating characteristic (AUROC) curve value of 0.908. The predictive performance of the maximum (max) change rate from D7 to the peak within M3 was also excellent (AUROC 0.949, = 0.580).
We clarified by a diagnostic study that sBAFF is not a diagnostic biomarker for ABMR in kidney transplantation and revealed by a nested case-control study that sBAFF values at M3 posttransplant and dynamic changes in sBAFF within M3 posttransplant have a good predictive value for the DSA/ABMR. It provides a useful tool for early screening of low-risk patients with negative preoperative DSA for the risk of developing postoperative DSA in kidney allograft recipients.
B 细胞激活因子（BAFF）在 B 细胞的激活和分化中起着关键作用，是抗体介导的排斥反应（ABMR）的候选诊断和预测生物标志物。我们旨在研究血清可溶性 BAFF（sBAFF）在肾移植后 ABMR 的诊断和风险分层中的价值。
在诊断研究中，比较了 ABMR（n=25）、T 细胞介导的排斥反应（TCMR）（n=14）、其他 4 种病理病变（n=21）和稳定同种异体移植物功能组（n=15）的 sBAFF 水平。在嵌套病例对照研究中，招募了伴有供体特异性抗体（DSA）或 ABMR（n=16）的肾移植受者与稳定同种异体移植物功能（n=7），并在移植前、术后 D7、M1、M3、M6、M9、M12、M18 进行 sBAFF 测量，并在移植后进行活检。
在 ABMR 和非 ABMR 组之间，活检时 sBAFF 水平没有显著差异。纵向研究表明，两组的 sBAFF 水平在 D7 时均急剧下降。DSA 组的 sBAFF 水平在 M1 开始升高，而在稳定组中，直到 M3 和 M6 才维持在低水平。DSA 组的 sBAFF 水平在 M1 [1,013.23（633.97,1,277.38）pg/ml 比 462.69（438.77,586.48）pg/ml， = 0.005]、M3 [1,472.07（912.79,1,922.08）pg/ml 比 561.63（489.77,630.00）pg/ml， = 0.002]和 M6 [1,217.95（965.25,1,321.43）pg/ml 比 726.93（604.77,924.60）pg/ml， = 0.027]时明显更高。M3 时的 sBAFF 水平对 DSA/ABMR 具有最佳的预测价值，ROC 曲线下面积（AUROC）值为 0.908。从 D7 到 M3 内峰值的最大（max）变化率的预测性能也非常出色（AUROC 0.949， = 0.580）。
我们通过诊断研究明确了 sBAFF 不是肾移植中 ABMR 的诊断生物标志物，并通过嵌套病例对照研究揭示了移植后 M3 时的 sBAFF 值和 M3 内 sBAFF 的动态变化对 DSA/ABMR 具有良好的预测价值。它为肾移植受者中术前阴性 DSA 的低风险患者提供了一种有用的工具，以早期筛查术后发生 DSA 的风险。
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