Melina U Melere, Flavia H Feier, Jorge Neumann, Antônio N Kalil, Juliana de M Montagner, Luiza S Nader, Carolina S da Silva, Marco Aurélio F Junior, Gabriela P Coral, Guilherme P Bobsin, Cristina T Ferreira
{"title":"小儿肝移植受者的人类白细胞抗原相容性和捐献者特异性抗体的发生率。","authors":"Melina U Melere, Flavia H Feier, Jorge Neumann, Antônio N Kalil, Juliana de M Montagner, Luiza S Nader, Carolina S da Silva, Marco Aurélio F Junior, Gabriela P Coral, Guilherme P Bobsin, Cristina T Ferreira","doi":"10.3748/wjg.v30.i33.3837","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of <i>de novo</i> 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.</p><p><strong>Aim: </strong>To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.</p><p><strong>Methods: </strong>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 <i>de novo</i> DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex<sup>®</sup> single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy.</p><p><strong>Results: </strong>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% <i>vs</i> 3%, <i>P</i> < 0.001). The rejection-free survival rates at 12 and 24 months were 76% <i>vs</i> 100% and 58% <i>vs</i> 95% for patients with dnDSA anti-DQ <i>vs</i> those without, respectively.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":23778,"journal":{"name":"World Journal of Gastroenterology","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438625/pdf/","citationCount":"0","resultStr":"{\"title\":\"Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.\",\"authors\":\"Melina U Melere, Flavia H Feier, Jorge Neumann, Antônio N Kalil, Juliana de M Montagner, Luiza S Nader, Carolina S da Silva, Marco Aurélio F Junior, Gabriela P Coral, Guilherme P Bobsin, Cristina T Ferreira\",\"doi\":\"10.3748/wjg.v30.i33.3837\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of <i>de novo</i> 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.</p><p><strong>Aim: </strong>To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.</p><p><strong>Methods: </strong>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 <i>de novo</i> DSA (dnDSA) was evaluated at least 3 months after LT using the Luminex<sup>®</sup> single antigen bead method, with a positive reaction threshold set at 1000 MFI. Rejection episodes were confirmed by liver biopsy.</p><p><strong>Results: </strong>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% <i>vs</i> 3%, <i>P</i> < 0.001). 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引用次数: 0
摘要
背景:肝移植(LT)术后抗体介导的排斥反应已被越来越多的人所认识,尤其是新出现的供体特异性抗体(DSA)及其对移植物寿命的影响。目的:调查人类白细胞抗原(HLA)错配和DSA的发生率,评估它们与小儿LT术后排斥反应的关系:2013年12月至2023年12月期间,在巴西阿雷格里港的Santa Casa接受HLA检测的一组儿科LT受者。只有在LT术后存活超过30天且至少进行过一次DSA分析的患者才被纳入。分析对象包括 I 类和 II 类 DSA 以及交叉配型。采用Luminex®单抗原珠法评估LT后至少3个月是否存在新生DSA(dnDSA),阳性反应阈值设定为1000 MFI。通过肝脏活检确认排斥反应:共分析了67名接受移植的儿童,其中61人接受了活体捐献者的移植,85%的受者与活体捐献者有亲属关系。28.3%的患者在移植前检测到DSA(I级或II级),48.4%的患者检测到dnDSA。LT后检测到DSA的中位时间为19.7个月[四分位距(IQR):4.3-35.6]。13名患者在随访时发生了活检证实的排斥反应,其中5/13例肝脏活检观察到C4d阳性。出现排斥反应的中位时间为 7.8 个月(IQR:5.7-12.8)。dnDSA的存在与排斥反应显著相关(36% vs 3%,P < 0.001)。有dnDSA抗DQ的患者与没有dnDSA抗DQ的患者相比,12个月和24个月的无排斥生存率分别为76% vs 100%和58% vs 95%:我们的研究结果凸显了将DSA评估纳入小儿LT受者移植前后方案的重要性。未来的影响可能包括根据这项分析为小儿LT受者制定免疫抑制最小化策略。
Human leukocyte antigen compatibility and incidence of donor-specific antibodies in pediatric liver transplant recipients.
Background: Antibody-mediated rejection following liver transplantation (LT) has been increasingly recognized, particularly with respect to the emergence of de novo 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.
Aim: To investigate the prevalence of human leukocyte antigen (HLA) mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.
Methods: 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 de novo 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.
Results: 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% vs 3%, P < 0.001). The rejection-free survival rates at 12 and 24 months were 76% vs 100% and 58% vs 95% for patients with dnDSA anti-DQ vs those without, respectively.
Conclusion: 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.
期刊介绍:
The primary aims of the WJG are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in gastroenterology and hepatology.