{"title":"同种异体造血细胞移植后移植物抗宿主病和巨细胞病毒再激活中单核髓源性抑制细胞恢复和白细胞介素-10产生的动力学","authors":"Arsa Thammahong , Kitsada Wudhikarn , Ponlapat Rojnuckarin , Patsita Kansuwan , Udomsak Bunworasate , Chantiya Chanswangphuwana","doi":"10.1016/j.trim.2025.102263","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Myeloid-derived suppressor cells (MDSCs) suppress immune responses. We hypothesized that MDSCs and their related cytokines/chemokines after receiving allogeneic hematopoietic cell transplantation (allo-HCT) impact graft-versus-host disease (GVHD) and infectious complications.</div></div><div><h3>Methods</h3><div>This study investigated the dynamics of MDSCs recovery using flow cytometry. Cytokines/chemokines were measured by the Luminex assay and correlated with clinical outcomes.</div></div><div><h3>Results</h3><div>Forty-nine patients who underwent allo-HCT at King Chulalongkorn Memorial Hospital from 2022 to 2023 were enrolled. The median age was 42 years. Most cases (81.6 %) were acute leukemia. Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (85.7 %) or haploidentical donors (14.3 %). Forty-six patients (93.9 %) received myeloablative conditioning regimens. GVHD prophylaxis regimens were calcineurin inhibitor plus methotrexate (67.3 %) and post-transplantation cyclophosphamide (32.7 %). Acute GVHD occurred in 9 (18.4 %) patients with a median onset of 35 days. The percentage of monocytic MDSC (M-MDSC), interleukin-10 (IL-10) and CXCL2 levels on day+28 of acute GVHD patients were all significantly lower than non-GVHD patients (0.26 % vs. 0.55 %, <em>p</em> = 0.048, 15.45 pg/ml vs. 23.53 pg/ml, <em>p</em> = 0.041, and 201.44 pg/ml vs. 428.42 pg/ml, <em>p</em> = 0.029, respectively). Cytomegalovirus (CMV) reactivation was detected in 69.4 % of patients with a median onset of 39 days. CMV reactivation was related to higher M-MDSC percentage on day+14 and IL-10 on day+28 compared with no reactivation (0.76 % vs. 0.22 %, <em>p</em> = 0.047 and 24.35 pg/ml vs. 16.42 pg/ml, <em>p</em> = 0.003, respectively).</div></div><div><h3>Conclusion</h3><div>Delayed M-MDSC reconstitution and low IL-10 were associated with acute GVHD, while high numbers of M-MDSCs and higher IL-10 levels increased the risk of CMV reactivation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"92 ","pages":"Article 102263"},"PeriodicalIF":1.4000,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dynamics of monocytic myeloid-derived suppressor cell recovery and interleukin-10 production on graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation\",\"authors\":\"Arsa Thammahong , Kitsada Wudhikarn , Ponlapat Rojnuckarin , Patsita Kansuwan , Udomsak Bunworasate , Chantiya Chanswangphuwana\",\"doi\":\"10.1016/j.trim.2025.102263\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Myeloid-derived suppressor cells (MDSCs) suppress immune responses. We hypothesized that MDSCs and their related cytokines/chemokines after receiving allogeneic hematopoietic cell transplantation (allo-HCT) impact graft-versus-host disease (GVHD) and infectious complications.</div></div><div><h3>Methods</h3><div>This study investigated the dynamics of MDSCs recovery using flow cytometry. Cytokines/chemokines were measured by the Luminex assay and correlated with clinical outcomes.</div></div><div><h3>Results</h3><div>Forty-nine patients who underwent allo-HCT at King Chulalongkorn Memorial Hospital from 2022 to 2023 were enrolled. The median age was 42 years. Most cases (81.6 %) were acute leukemia. Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (85.7 %) or haploidentical donors (14.3 %). Forty-six patients (93.9 %) received myeloablative conditioning regimens. GVHD prophylaxis regimens were calcineurin inhibitor plus methotrexate (67.3 %) and post-transplantation cyclophosphamide (32.7 %). Acute GVHD occurred in 9 (18.4 %) patients with a median onset of 35 days. The percentage of monocytic MDSC (M-MDSC), interleukin-10 (IL-10) and CXCL2 levels on day+28 of acute GVHD patients were all significantly lower than non-GVHD patients (0.26 % vs. 0.55 %, <em>p</em> = 0.048, 15.45 pg/ml vs. 23.53 pg/ml, <em>p</em> = 0.041, and 201.44 pg/ml vs. 428.42 pg/ml, <em>p</em> = 0.029, respectively). Cytomegalovirus (CMV) reactivation was detected in 69.4 % of patients with a median onset of 39 days. CMV reactivation was related to higher M-MDSC percentage on day+14 and IL-10 on day+28 compared with no reactivation (0.76 % vs. 0.22 %, <em>p</em> = 0.047 and 24.35 pg/ml vs. 16.42 pg/ml, <em>p</em> = 0.003, respectively).</div></div><div><h3>Conclusion</h3><div>Delayed M-MDSC reconstitution and low IL-10 were associated with acute GVHD, while high numbers of M-MDSCs and higher IL-10 levels increased the risk of CMV reactivation.</div></div>\",\"PeriodicalId\":23304,\"journal\":{\"name\":\"Transplant immunology\",\"volume\":\"92 \",\"pages\":\"Article 102263\"},\"PeriodicalIF\":1.4000,\"publicationDate\":\"2025-06-25\",\"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/S0966327425000917\",\"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/S0966327425000917","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
骨髓源性抑制细胞(MDSCs)可抑制免疫反应。我们假设接受同种异体造血细胞移植(alloc - hct)后的MDSCs及其相关细胞因子/趋化因子影响移植物抗宿主病(GVHD)和感染性并发症。方法采用流式细胞术研究MDSCs的恢复动态。细胞因子/趋化因子通过Luminex检测并与临床结果相关。结果入选2022 - 2023年在朱拉隆功国王纪念医院接受同种异体ct治疗的49例患者。中位年龄为42岁。多数为急性白血病(81.6%)。外周血干细胞采集自人类白细胞抗原匹配相关/非相关供者(85.7%)或单倍体相同供者(14.3%)。46例(93.9%)患者接受了清髓调节方案。GVHD预防方案为钙调磷酸酶抑制剂加甲氨蝶呤(67.3%)和移植后环磷酰胺(32.7%)。9例(18.4%)患者发生急性GVHD,中位发病时间为35天。急性GVHD患者+28天单核细胞MDSC (M-MDSC)百分比、白细胞介素-10 (IL-10)和CXCL2水平均显著低于非GVHD患者(分别为0.26%比0.55%,p = 0.048, 15.45 pg/ml比23.53 pg/ml, p = 0.041, 201.44 pg/ml比428.42 pg/ml, p = 0.029)。在中位发病时间为39天的患者中检测到69.4%的巨细胞病毒(CMV)再激活。CMV再激活与未激活组相比,第14天的M-MDSC百分比和第28天的IL-10百分比较高(分别为0.76%对0.22%,p = 0.047和24.35 pg/ml对16.42 pg/ml, p = 0.003)。结论M-MDSC重构延迟和IL-10水平低与急性GVHD相关,而M-MDSC数量高和IL-10水平高会增加CMV再激活的风险。
Dynamics of monocytic myeloid-derived suppressor cell recovery and interleukin-10 production on graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation
Background
Myeloid-derived suppressor cells (MDSCs) suppress immune responses. We hypothesized that MDSCs and their related cytokines/chemokines after receiving allogeneic hematopoietic cell transplantation (allo-HCT) impact graft-versus-host disease (GVHD) and infectious complications.
Methods
This study investigated the dynamics of MDSCs recovery using flow cytometry. Cytokines/chemokines were measured by the Luminex assay and correlated with clinical outcomes.
Results
Forty-nine patients who underwent allo-HCT at King Chulalongkorn Memorial Hospital from 2022 to 2023 were enrolled. The median age was 42 years. Most cases (81.6 %) were acute leukemia. Peripheral blood stem cells were collected from human leukocyte antigen-matched related/unrelated donors (85.7 %) or haploidentical donors (14.3 %). Forty-six patients (93.9 %) received myeloablative conditioning regimens. GVHD prophylaxis regimens were calcineurin inhibitor plus methotrexate (67.3 %) and post-transplantation cyclophosphamide (32.7 %). Acute GVHD occurred in 9 (18.4 %) patients with a median onset of 35 days. The percentage of monocytic MDSC (M-MDSC), interleukin-10 (IL-10) and CXCL2 levels on day+28 of acute GVHD patients were all significantly lower than non-GVHD patients (0.26 % vs. 0.55 %, p = 0.048, 15.45 pg/ml vs. 23.53 pg/ml, p = 0.041, and 201.44 pg/ml vs. 428.42 pg/ml, p = 0.029, respectively). Cytomegalovirus (CMV) reactivation was detected in 69.4 % of patients with a median onset of 39 days. CMV reactivation was related to higher M-MDSC percentage on day+14 and IL-10 on day+28 compared with no reactivation (0.76 % vs. 0.22 %, p = 0.047 and 24.35 pg/ml vs. 16.42 pg/ml, p = 0.003, respectively).
Conclusion
Delayed M-MDSC reconstitution and low IL-10 were associated with acute GVHD, while high numbers of M-MDSCs and higher IL-10 levels increased the risk of CMV reactivation.
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.