活体大叶肺移植术后早期临床诊断急性排斥反应中抗供体CD8同种免疫反应的激活及其对预后的影响

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2025-02-21 DOI:10.1016/j.trim.2025.102201

Satona Tanaka , Naoki Tanimine , Akiyoshi Nakakura , Koichiro Uchida , Ichiro Sakanoue , Hidenao Kayawake , Mamoru Takahashi , Shigeto Nishikawa , Yojiro Yutaka , Yoshito Yamada , Akihiro Ohsumi , Masatsugu Hamaji , Daisuke Nakajima , Toyofumi F. Chen-Yoshikawa , Yuka Tanaka , Hideki Ohdan , Hiroshi Date

{"title":"活体大叶肺移植术后早期临床诊断急性排斥反应中抗供体CD8同种免疫反应的激活及其对预后的影响","authors":"Satona Tanaka , Naoki Tanimine , Akiyoshi Nakakura , Koichiro Uchida , Ichiro Sakanoue , Hidenao Kayawake , Mamoru Takahashi , Shigeto Nishikawa , Yojiro Yutaka , Yoshito Yamada , Akihiro Ohsumi , Masatsugu Hamaji , Daisuke Nakajima , Toyofumi F. Chen-Yoshikawa , Yuka Tanaka , Hideki Ohdan , Hiroshi Date","doi":"10.1016/j.trim.2025.102201","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The characteristics and prognostic impacts of early graft infiltration after lung transplantation and clinically diagnosed acute rejection remain unclear. Furthermore, the alloimmune response status in lung transplantation remains uninvestigated.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study, we evaluated 92 living-donor lobar lung transplantations (LDLLT) to establish the effect of graft infiltration—diagnosed as acute rejection—within one-month post-transplantation (cAR), on chronic lung allograft dysfunction (CLAD)-free LDLLT survival. The alloimmune response was evaluated using the carboxyfluorescein diacetate succinimidyl ester (CFSE)-mixed lymphocyte reaction (MLR) in lymphocytes isolated from donor and recipient blood one week after LDLLT. The anti-donor proliferation of CD4+ and CD8+ T cells was determined using flow cytometry.</div></div><div><h3>Results</h3><div>cAR was observed in 54 (58.7 %) patients who underwent LDLLT. The median postoperative day of cAR occurrence was 7 days (ranging between 5 and 28 days). Only one episode of cAR occurred in 51 patients (94.4 %). CLAD-free survival was significantly lower in patients who underwent cAR, especially within 2 years after LDLLT (<em>p</em> = 0.016). Thirteen CFSE-MLR assays were performed in seven consecutive LDLLT cases (six bilateral and one unilateral LDLLT). Increased anti-donor proliferation of CD8+ T cells, but not CD4+ T cells, was associated with cAR, irrespective of human leukocyte antigen (HLA) class I mismatch.</div></div><div><h3>Conclusion</h3><div>Early lung graft infiltration after LDLLT increases the risk of the early development of CALD. Augmented anti-donor CD8 + response was also associated with graft infiltration, which could not be predicted from HLA mismatches but could be monitored using MLR in LDLLT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102201"},"PeriodicalIF":1.6000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Activation of anti-donor CD8 alloimmune response in clinically diagnosed acute rejection early after living-donor lobar lung transplantation and its impact on outcome\",\"authors\":\"Satona Tanaka , Naoki Tanimine , Akiyoshi Nakakura , Koichiro Uchida , Ichiro Sakanoue , Hidenao Kayawake , Mamoru Takahashi , Shigeto Nishikawa , Yojiro Yutaka , Yoshito Yamada , Akihiro Ohsumi , Masatsugu Hamaji , Daisuke Nakajima , Toyofumi F. Chen-Yoshikawa , Yuka Tanaka , Hideki Ohdan , Hiroshi Date\",\"doi\":\"10.1016/j.trim.2025.102201\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>The characteristics and prognostic impacts of early graft infiltration after lung transplantation and clinically diagnosed acute rejection remain unclear. Furthermore, the alloimmune response status in lung transplantation remains uninvestigated.</div></div><div><h3>Methods</h3><div>In this retrospective cohort study, we evaluated 92 living-donor lobar lung transplantations (LDLLT) to establish the effect of graft infiltration—diagnosed as acute rejection—within one-month post-transplantation (cAR), on chronic lung allograft dysfunction (CLAD)-free LDLLT survival. The alloimmune response was evaluated using the carboxyfluorescein diacetate succinimidyl ester (CFSE)-mixed lymphocyte reaction (MLR) in lymphocytes isolated from donor and recipient blood one week after LDLLT. The anti-donor proliferation of CD4+ and CD8+ T cells was determined using flow cytometry.</div></div><div><h3>Results</h3><div>cAR was observed in 54 (58.7 %) patients who underwent LDLLT. The median postoperative day of cAR occurrence was 7 days (ranging between 5 and 28 days). Only one episode of cAR occurred in 51 patients (94.4 %). CLAD-free survival was significantly lower in patients who underwent cAR, especially within 2 years after LDLLT (<em>p</em> = 0.016). Thirteen CFSE-MLR assays were performed in seven consecutive LDLLT cases (six bilateral and one unilateral LDLLT). Increased anti-donor proliferation of CD8+ T cells, but not CD4+ T cells, was associated with cAR, irrespective of human leukocyte antigen (HLA) class I mismatch.</div></div><div><h3>Conclusion</h3><div>Early lung graft infiltration after LDLLT increases the risk of the early development of CALD. Augmented anti-donor CD8 + response was also associated with graft infiltration, which could not be predicted from HLA mismatches but could be monitored using MLR in LDLLT.</div></div>\",\"PeriodicalId\":23304,\"journal\":{\"name\":\"Transplant immunology\",\"volume\":\"90 \",\"pages\":\"Article 102201\"},\"PeriodicalIF\":1.6000,\"publicationDate\":\"2025-02-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Transplant immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0966327425000292\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplant immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0966327425000292","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景肺移植术后早期移植物浸润及临床诊断急性排斥反应的特点和预后影响尚不清楚。此外，同种免疫反应在肺移植中的地位仍未得到研究。方法在这项回顾性队列研究中，我们评估了92例活体供体大叶肺移植（LDLLT），以确定移植后1个月内移植物浸润（诊断为急性排斥反应）对慢性同种异体肺移植功能障碍（CLAD）无LDLLT存活的影响。在LDLLT后1周，用羧基荧光素-二乙酸琥珀酰酰酯(CFSE)-混合淋巴细胞反应（MLR）评价供体和受体分离淋巴细胞的同种免疫反应。流式细胞术检测CD4+和CD8+ T细胞抗供体增殖。结果54例（58.7%）LDLLT患者出现瘢痕。术后cAR发生的中位天数为7天（范围为5 ~ 28天）。51例患者（94.4%）仅发生一次cAR发作。接受cAR治疗的患者无clad生存率显著降低，尤其是LDLLT后2年内（p = 0.016）。连续7例LDLLT患者（6例双侧LDLLT和1例单侧LDLLT）进行13次CFSE-MLR检测。无论人类白细胞抗原（HLA） I类失配与否，抗供体CD8+ T细胞增殖增加与cAR相关，而CD4+ T细胞不存在。结论LDLLT术后早期肺移植物浸润增加CALD早期发展的风险。增强的抗供体CD8 +反应也与移植物浸润有关，这不能通过HLA不匹配来预测，但可以通过LDLLT的MLR来监测。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Activation of anti-donor CD8 alloimmune response in clinically diagnosed acute rejection early after living-donor lobar lung transplantation and its impact on outcome

查看原文本刊更多论文

Activation of anti-donor CD8 alloimmune response in clinically diagnosed acute rejection early after living-donor lobar lung transplantation and its impact on outcome

Background

The characteristics and prognostic impacts of early graft infiltration after lung transplantation and clinically diagnosed acute rejection remain unclear. Furthermore, the alloimmune response status in lung transplantation remains uninvestigated.

Methods

In this retrospective cohort study, we evaluated 92 living-donor lobar lung transplantations (LDLLT) to establish the effect of graft infiltration—diagnosed as acute rejection—within one-month post-transplantation (cAR), on chronic lung allograft dysfunction (CLAD)-free LDLLT survival. The alloimmune response was evaluated using the carboxyfluorescein diacetate succinimidyl ester (CFSE)-mixed lymphocyte reaction (MLR) in lymphocytes isolated from donor and recipient blood one week after LDLLT. The anti-donor proliferation of CD4+ and CD8+ T cells was determined using flow cytometry.

Results

cAR was observed in 54 (58.7 %) patients who underwent LDLLT. The median postoperative day of cAR occurrence was 7 days (ranging between 5 and 28 days). Only one episode of cAR occurred in 51 patients (94.4 %). CLAD-free survival was significantly lower in patients who underwent cAR, especially within 2 years after LDLLT (p = 0.016). Thirteen CFSE-MLR assays were performed in seven consecutive LDLLT cases (six bilateral and one unilateral LDLLT). Increased anti-donor proliferation of CD8+ T cells, but not CD4+ T cells, was associated with cAR, irrespective of human leukocyte antigen (HLA) class I mismatch.

Conclusion

Early lung graft infiltration after LDLLT increases the risk of the early development of CALD. Augmented anti-donor CD8 + response was also associated with graft infiltration, which could not be predicted from HLA mismatches but could be monitored using MLR in LDLLT.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.