Department of Hepatology and Liver Transplantation, Santa Casa de Porto Alegre, Porto Alegre 90050170, Rio Grande do Sul, Brazil.
Department of Hepato-biliary-pancreatic Surgery and Liver Transplantation, Irmandade Santa Casa de Misericórdia de Porto Alegre, Porto Alegre 90020-090, Rio Grande do Sul, Brazil.
World J Gastroenterol. 2024 Sep 7;30(33):3837-3845. doi: 10.3748/wjg.v30.i33.3837.
Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of donor-specific antibodies (DSAs) and their impact on graft longevity. While substantial evidence for adult populations exists, research focusing on pediatric LT outcomes remains limited.
To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.
A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre, Brazil, between December 2013 and December 2023. Only patients who survived for > 30 days after LT with at least one DSA analysis were included. DSA classes I and II and cross-matches were analyzed. The presence of DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy.
Overall, 67 transplanted children were analyzed; 61 received grafts from living donors, 85% of whom were related to recipients. Pre-transplant DSA (class I or II) was detected in 28.3% of patients, and dnDSA was detected in 48.4%. The median time to DSA detection after LT was 19.7 [interquartile range (IQR): 4.3-35.6] months. Biopsy-proven rejection occurred in 13 patients at follow-up, with C4d positivity observed in 5/13 Liver biopsies. The median time to rejection was 7.8 (IQR: 5.7-12.8) months. The presence of dnDSA was significantly associated with rejection (36% 3%, < 0.001). The rejection-free survival rates at 12 and 24 months were 76% 100% and 58% 95% for patients with dnDSA anti-DQ those without, respectively.
Our findings highlight the importance of incorporating DSA assessment into pre- and post-transplantation protocols for pediatric LT recipients. Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.
肝移植（LT）后抗体介导的排斥反应（AMR）已逐渐被认识到，特别是在供体特异性抗体（DSA）的出现及其对移植物长期存活的影响方面。虽然有大量针对成人的证据，但针对儿科 LT 结果的研究仍然有限。
调查人类白细胞抗原（HLA）错配和 DSA 的流行情况，并评估其与儿科 LT 后排斥反应发作的关系。
巴西阿雷格里港圣家堂的一组儿科 LT 受者在 2013 年 12 月至 2023 年 12 月期间接受 HLA 检测。仅纳入 LT 后存活时间超过 30 天且至少进行了一次 DSA 分析的患者。分析了 DSA Ⅰ类和Ⅱ类和交叉配型。在 LT 后至少 3 个月使用 Luminex 单抗原珠法评估 dnDSA（存在），阳性反应阈值设定为 1000 MFI。通过肝活检确认排斥反应发作。
共分析了 67 名接受移植的儿童；61 名接受活体供者的移植物，其中 85%与受者有亲属关系。28.3%的患者在移植前检测到预存 DSA（Ⅰ类或Ⅱ类），48.4%的患者检测到 dnDSA。LT 后检测到 DSA 的中位时间为 19.7 [四分位距（IQR）：4.3-35.6]个月。在随访期间，13 名患者发生活检证实的排斥反应，5/13 例肝活检显示 C4d 阳性。排斥反应的中位时间为 7.8（IQR：5.7-12.8）个月。dnDSA 的存在与排斥反应显著相关（36% 3%， < 0.001）。dnDSA 阳性患者的 12 个月和 24 个月无排斥反应生存率分别为 76% 100%和 58% 95%，而 dnDSA 阴性患者分别为 71% 97%和 52% 96%。
我们的研究结果强调了在儿科 LT 受者的移植前和移植后方案中纳入 DSA 评估的重要性。未来的影响可能包括基于此分析的儿科 LT 受者的免疫抑制最小化策略。
