Transplant immunology最新文献

{"title":"Trametinib alleviates lipopolysaccharide-induced acute kidney injury by inhibiting macrophage polarization through the PI3K/Akt pathway","authors":"Yingqi Zeng ,&nbsp;Wenjia Yuan ,&nbsp;Chen Feng ,&nbsp;Longkai Peng ,&nbsp;Xubiao Xie ,&nbsp;Fenghua Peng ,&nbsp;Tengfang Li ,&nbsp;Minjie Lin ,&nbsp;Hedong Zhang ,&nbsp;Helong Dai","doi":"10.1016/j.trim.2025.102183","DOIUrl":"10.1016/j.trim.2025.102183","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced acute kidney injury (AKI) is a severe condition characterized by dysregulation of pro- and anti-inflammatory responses. Targeting macrophage polarization between pro-inflammatory M1 and anti-inflammatory M2 cells offers a potential therapeutic approach for AKI. Trametinib (TRAM), an inhibitor of the MEK1/2 signaling pathway, was evaluated for its impact on M1/M2 polarization in AKI.</div></div><div><h3>Methods</h3><div>Wild-type (WT) mice were subjected to lipopolysaccharide (LPS)-induced AKI and intraperitoneally treated with dimethyl sulfoxide (DMSO) or TRAM (10 mg/kg) for three days. Renal function was assessed by measuring creatinine levels. While histopathological changes, RNA sequencing data, and serum cytokine levels were analyzed. Macrophage M1/M2 polarization in kidney tissues was examined using flow cytometry and immunohistochemistry. Murine bone marrow-derived macrophages (BMDMs) were polarized to the M1 or M2 phenotype in vivo and treated with or without TRAM (10 μM). M1/M2 polarization was analyzed via flow cytometry, and PI3K/Akt signaling was evaluated by western blotting.</div></div><div><h3>Results</h3><div>TRAM significantly improved renal function, as demonstrated by reduced serum creatinine levels (<em>p</em> &lt; 0.01) and ameliorated histopathological damage (p &lt; 0.01). Flow cytometry and immunohistochemistry revealed that TRAM markedly inhibited pro-inflammatory M1 macrophage polarization (<em>p</em> &lt; 0.001). Additionally, TRAM reduced serum level of IFN-γ (<em>p</em> &lt; 0.01) and IL-17 (p &lt; 0.001). In vitro, TRAM suppressed M1 polarization (<em>p</em> &lt; 0.05) by inhibiting the PI3K/Akt signaling pathway.</div></div><div><h3>Conclusion</h3><div>TRAM mitigated LPS-induced AKI by suppressing M1 macrophage polarization via the PI3K/Akt pathway, highlighting its therapeutic potential for AKI and other inflammatory kidney diseases.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102183"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of human leukocyte antigen (HLA) allele and haplotype frequency using next generation sequencing (NGS) platform: Single-centre study of over 500 individuals in India!","authors":"Mehra Simmi,&nbsp;Aseem K Tiwari,&nbsp;Chauhan Rajni,&nbsp;Bhardwaj Gunjan,&nbsp;Rani Neha,&nbsp;Kashyap Shubham,&nbsp;Kahlon Simran","doi":"10.1016/j.trim.2025.102180","DOIUrl":"10.1016/j.trim.2025.102180","url":null,"abstract":"<div><h3>Background</h3><div>The huge diversity of Human Leukocyte Antigen (HLA) system is well-known to be associated with various diseases, anthropology, population genetics, and transplantation. The frequencies of HLA alleles in different populations are crucial for both research and clinical applications. This study determined the allelic and haplotype frequencies of all HLA class I and class II loci in 595 consecutive samples from patients who underwent solid organ transplantation (SOT) and hematopoietic progenitor cell transplantation (HPCT).</div></div><div><h3>Method</h3><div>High-resolution HLA typing for HLA-A, B, C, DRB1, and DQB1 was conducted using a next generation sequencing (NGS) platform.</div></div><div><h3>Results</h3><div>The most frequent alleles observed among all HLAs were A*11:01:01 (0.1849), A*24:02:01 (0.1202) and A*01:01:01 (0.1143) in A locus, B*40:06:01 (0.1050), B*52:01:01 (0.0950) and B*51:01:01 (0.0723) in B locus, C*07:02:01 (0.1303), C*04:01:01 (0.1227) and C*15:02:01 (0.1185) in C locus, DRB1*07:01:01 (0.1286), DRB1*15:01:01 (0.1134) and DRB1*03:01:01 (0.0966) in DRB1 locus, and DQB1*06:01:01 (0.1849), DQB1*03:01:01 (0.1471) and DQB1*02:02:01 (0.0966) in DQB1 locus. The most frequent (&gt;2 %) five-locus A ∼ B ∼ C ∼ DRB1 ∼ DQB1 haplotypes were A*33:03:01 ∼ B*44:03:02 ∼ C*07:06:01 ∼ DQB1*02:02:01 ∼ DRB1*07:01:01 (2.97 %), A*26:01:01 ∼ B*08:01:01 ∼ C*07:02:01 ∼ DQB1*02:01:01 ∼ DRB1*03:01:01 (2.23 %) and A*02:11:01 ∼ B*40:06:01 ∼ C*15:02:01 ∼ DQB1*06:01:01 ∼ DRB1*15:01:01(2.15 %). Among all tested loci, the HLA-B locus had the most polymorphism, whereas the HLA-DQB1 locus had the least polymorphism.</div></div><div><h3>Conclusion</h3><div>The data represent the distribution of HLA-A, B, C, DRB1, DQB1 alleles and their haplotype frequencies among the population in India.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102180"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effective management of primary central nervous system posttransplant lymphoproliferative disorder in a kidney transplant recipient using surgery and rituximab, along with a literature review","authors":"Guangjun Liu ,&nbsp;Rending Wang ,&nbsp;Jianyong Wu ,&nbsp;Jianghua Chen","doi":"10.1016/j.trim.2025.102186","DOIUrl":"10.1016/j.trim.2025.102186","url":null,"abstract":"<div><h3>Background</h3><div>Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare but severe complication following solid organ transplantation (SOT). Currently, treatment regimens still lack clear guidelines.</div></div><div><h3>Methods</h3><div>A kidney transplant recipient with PCNS-PTLD was reported in this case study, who treated with rituximab after transplant surgery. What's more, PubMed was used to find case series related to PCNS-PTLD.</div></div><div><h3>Results</h3><div>The patient of this case report experienced complete remission (CR) following resection and treatment with rituximab. A total of 130 cases were extracted from 20 articles and were combined with one case from our institution. Out of 131 patients with PCNS-PTLD, the median duration between SOT and PTLD was 48 months. The majority (83 %) of patients had received a kidney transplant, with 74.8 % showing monomorphic histology and 93 % having an EBV+ tumor. Most patients (95 %) had reduction in immunosuppression as part of their first-line treatment. Other initial treatments consisted of high-dose methotrexate (HD-MTX) (46 %), high-dose cytarabine (HDAC) (26 %), and/or rituximab (47 %). The Overall Response Rate (ORR) was 63 %, showing that HD-MTX and/or HDAC-based therapy had the highest rates of ORR and CR. Roughly half of the participants experienced prolonged survival. After 36 months of observation, the median progression free survival (PFS) was 10 months and the overall survival (OS) was 18 months.</div></div><div><h3>Conclusion</h3><div>The use of HD-MTX and HDAC showed promise in treating PCNS-PTLD, but rituximab may also a potential drug for the PCNS-PTLD. Research should continue to investigate the alternative treatments for this condition.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"90 ","pages":"Article 102186"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsp90 and HIF-1α regulate mitophagy by promoting BNIP3 expression in renal ischemia-reperfusion injury","authors":"Qi Dong,&nbsp;Xia Li,&nbsp;Ke Cheng","doi":"10.1016/j.trim.2025.102177","DOIUrl":"10.1016/j.trim.2025.102177","url":null,"abstract":"<div><h3>Background</h3><div>Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI). Studies have shown that mitochondrial damage is involved in the pathogenesis of AKI, and that inhibition of Hsp90 expression can improve IR-induced AKI. However, the mechanisms by which Hsp90 improves IR-induced AKI and whether it is involved in mitochondrial autophagy remain unclear.</div></div><div><h3>Methods</h3><div>An IR-induced AKI mouse model was established, and the degree of renal injury was analyzed using hematoxylin and eosin (H&amp;E) and periodic acid-Schiff (PAS) staining. The expression of Hsp90, HIF-1α, BNIP3, and mitochondrial autophagy proteins was detected by western blotting <em>in vivo</em> and <em>in vitro</em>. HK2 cell viability, apoptosis, mitochondrial autophagy, reactive oxygen species (ROS), and inflammatory cytokines levels were detected using Cell Counting Kit 8 (CCK8) assays, Terminal·deoxynucleotidyl transferase-mediated dUTP nick end·labeling (TUNEL) labeling, immunofluorescence, and enzyme-linked immunosorbent (ELISA).</div></div><div><h3>Results</h3><div>A murine IR-induced AKI model was successfully generated, and increased expression levels of Hsp90, HIF-1α, and inflammatory cytokines were observed, accompanied by a worsening of renal injury. After induction of IRI in HK2 cells, downregulation of Hsp90 or HIF-1α expression resulted in decreased downstream BNIP3 expression, an increase in HK2 cell viability, and a decrease in the level of mitochondrial autophagy.</div></div><div><h3>Conclusion</h3><div>Hsp90 upregulated the expression of HIF-1αand BNIP3, thereby enhancing mitochondrial autophagy in IR-induced AKI.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102177"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of tacrolimus time in therapeutic range (TTR) on early post transplantation outcomes","authors":"Mariano Berro MD PhD ,&nbsp;Silvina Odstrcil MD ,&nbsp;Milagros Frassa MD ,&nbsp;Maria M. Rivas MD ,&nbsp;Jose I Trucco ,&nbsp;Ines Paganini MD ,&nbsp;Gustavo D. Kusminsky MD ,&nbsp;Daniel Couriel MD","doi":"10.1016/j.trim.2025.102181","DOIUrl":"10.1016/j.trim.2025.102181","url":null,"abstract":"<div><div>Tacrolimus is a backbone for immunosuppression after allogeneic stem cell transplantation (AlloSCT). There is no sufficient kinetic data demonstrating the consistency of maintaining therapeutic levels. Herein, we measured the kinetic of therapeutic range (TTR) and its impact on outcomes of AlloSCT. Our local observational cohort included 186 adult AlloSCT performed at Hospital Austral between January 2012 and December 2019. An additional external cohort included 307 adult patients with AlloSCT from the University of Utah. We defined adequate TTR as &gt;75 % of the measurements between 5.0 and 15.0 ng/mL during the first 30 days post-transplantation. In our local cohort, 55 % of patients had adequate TTR values. Primary graft failure was significantly lower in patients with adequate TTR (2 %, 95 % CI 0.5–7.7 % vs. 10 %, 95 % CI 5–18 %, <em>p</em> = 0.01). Non relapse mortality (NRM) was significantly lower with adequate TTR (17 %, 95 % CI 11–26 % vs. 33 %, 95 % CI 24–43 %; <em>p</em> &lt; 0.01). Similarly, the external cohort had an NRM value significantly reduced in patients with adequate TTR values. In the pooled data analysis of local and external groups (<em>n</em> = 493), the TTR value below minimal range (≥25 % of measurements &lt;5 ng/mL) was an independent risk factor for graft failure, as well as for NRM rate (44 %, 95 % CI 30–57 % vs. 18 %, 95 % CI 15–22 %) (<em>p</em> &lt; 0.001) and lower OS at 3 years (47 %, 95 % CI 26–55 % vs. 56 %, 95 % CI 49–59 %, p &lt; 0.001).</div><div>These findings showed the importance of adequate TTRs during the first month after AlloSCTs. Sub-therapeutic TTR values were associated with worse survival outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102181"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel CD62L depleted donor lymphocyte infusion with T-cell receptor alpha-beta depleted haploidentical hematopoietic stem cell transplantation in children","authors":"Daniel Ka Leung Cheuk ,&nbsp;Pamela Pui Wah Lee ,&nbsp;Wilson Yau Ki Chan ,&nbsp;Godfrey Chi Fung Chan ,&nbsp;Chi Chiu So ,&nbsp;Wing Hang Leung","doi":"10.1016/j.trim.2025.102176","DOIUrl":"10.1016/j.trim.2025.102176","url":null,"abstract":"<div><div>Ex-vivo depletion of donor CD45RA+ naïve T-cells can reduce graft-versus-host-disease (GVHD) in haploidentical hematopoietic stem cell transplantation (HSCT) while providing memory T-cells to reduce infections. CD62L is another marker of naïve T-cells. Depletion of CD62L+ cells may offer advantages of removing central memory T-cells which may also cause mild GVHD, and retain CD45RA+ effector memory T-cells (TEMRA). We aimed to evaluate the depletion efficiency, safety and immunoreconstitution after novel CD62L depleted donor lymphocyte infusion (DLI) with T-cell receptor (TCR)-αβ depleted haploidentical HSCT. Children with malignant or non-malignant diseases who underwent the first TCRαβ depleted haploidentical HSCT were recruited to receive CD62L depleted DLI on day 0 at a dose of 1 × 10⁶/kg or 5 × 10⁶/kg CD3+CD62L- cells using the CliniMACS device. Six children aged 0.3–15 years received 4.6-10 × 10⁶/kg CD34+ cells. CD62L depletion resulted in undetectable CD3+CD62L+ cells in 4 patients and 3.39–3.52 log reduction in 2 patients. Infusion was well-tolerated. All patients had neutrophil and platelet engrafted early (medians 10 and 9.5 days respectively) with 100 % donor chimerism. Only one patient had grade 1 acute GVHD. None had chronic GVHD. Post-transplant recovery of CD3+ cells reached a median of 117/uL at 1 month and as high as 352/uL at 3 months. TEMRA cells were present at 1 month (median 2 cells/uL) and increased 3 months post-transplant (median 21 cells/uL). In conclusion, CD62L depletion is highly efficient and appears safe and does not affect engraftment. It provides TEMRA and effector memory T-cells to protect the recipient against infections. Risk of GVHD is low.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102176"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical application of biological agents in rheumatoid arthritis","authors":"Lianying Cheng ,&nbsp;Xiaofeng Rong","doi":"10.1016/j.trim.2025.102187","DOIUrl":"10.1016/j.trim.2025.102187","url":null,"abstract":"<div><div>Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder primarily distinguished by synovial inflammation, which, as the disease evolves, can lead to bone erosion and destruction. Consequently, the pivotal strategy in preventing joint damage and fostering functional recovery lies in the effective management of synovial inflammation. Disease-modifying antirheumatic drugs (DMARDs) and prednisone therapy remain the first-line treatments for RA. However, in instances of refractory RA, these medications may fall short in adequately controlling inflammation, and they are often accompanied by several adverse effects, including limited bioavailability, therapeutic resistance, and potentially toxic side effects. Given these challenges, the identification of targeted therapies to manage disease activity and diminish inflammation becomes imperative.Recently, biologic agents for the treatment of RA have garnered significant attention owing to their minimal side effect profile, reduced potential for drug dependence, and their precise therapeutic action directly on target cells. This review provides a comprehensive exploration of advancements in biologics that target and inhibit inflammatory cytokine receptors, specifically TNF-α, IL-6, and IL-1β, as well as B lymphocyte receptors, TLR4, nanodrugs, and Janus kinase (JAK) inhibitors in the context of RA. By providing innovative perspectives and strategies for the treatment of this condition, this review contributes to the ongoing efforts to refine and improve the therapeutic landscape for RA.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102187"},"PeriodicalIF":1.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing the urobiome and associated metabolic profiles during acute rejection in renal transplant patients: A pilot study","authors":"David Harriman ,&nbsp;Alex Ng ,&nbsp;Monica Bronowski ,&nbsp;Herman Kazakov ,&nbsp;Christopher Nguan ,&nbsp;Thien Dang ,&nbsp;Karen Sherwood ,&nbsp;Aaron Miller ,&nbsp;Dirk Lange","doi":"10.1016/j.trim.2024.102170","DOIUrl":"10.1016/j.trim.2024.102170","url":null,"abstract":"<div><div>Characteristic alterations in the urinary microbiome, or urobiome, are associated with renal transplant pathology. To date, there has been no direct study of the urobiome during acute allograft rejection. The goal of this study was to determine if unique urobiome alterations are present during acute rejection in renal transplant recipients. We performed shotgun metagenomic sequencing of 32 mid-stream urine samples obtained from 15 transplant recipients pre-transplant, 1- and 3-months post-transplant, and at time of rejection discovered with for-cause biopsy. Within individuals, there was a 40–60 % difference in urobiome composition from pre-to-post-transplant in both rejectors and non-rejectors. The taxa Ureaplasma was enriched in rejectors compared to non-rejectors. However, a greater number of microbial genes were enriched in non-rejectors compared to rejectors, except for genes associated with tetracycline resistance, the lysophosphatidic acid synthesis pathway, and tryptophanyl-tRNA synthetase. Together, our findings suggest that the urobiome is significantly altered post-transplant with certain taxa and/or microbial genes potentially associated with acute allograft rejection/inflammation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102170"},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142955673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lower basophil count after anti-thymocyte globulin induction is associated with lower incidence of acute cellular rejection in heart transplant recipients","authors":"Boško Skorić ,&nbsp;Petra Mjehović ,&nbsp;Mia Dubravčić Došen ,&nbsp;Andrija Nekić ,&nbsp;Dora Fabijanović ,&nbsp;Nina Jakuš ,&nbsp;Jure Samardžić ,&nbsp;Ivo Planinc ,&nbsp;Maja Čikeš ,&nbsp;Hrvoje Gašparović ,&nbsp;Davor Miličić","doi":"10.1016/j.trim.2025.102173","DOIUrl":"10.1016/j.trim.2025.102173","url":null,"abstract":"<div><h3>Introduction</h3><div>While lymphodepletion is considered a therapeutic effect of rabbit anti-thymocyte globulin (rATG), a concomitant decrease in basophil count (BC) has unknown clinical effect.</div></div><div><h3>Objective</h3><div>To investigate the association between BC following rATG induction and acute cellular rejection (ACR) during the first post-HTx year.</div></div><div><h3>Methods</h3><div>Retrospective single-center study included 183 HTx recipients receiving rATG induction between 2010 and 2021 (mean age 52 ± 13 years, 23 % female). Absolute lymphocyte count (ALC), platelet (PLT) count and BC were assessed on days 0, 7, 14, and 21 following HTx. The primary outcome was the first ACR (grade ≥1B) within the first post-HTx year.</div></div><div><h3>Results</h3><div>Patients with ACR had significantly higher BC on day 14 (17/μL (IQR 9–43/μL) vs. 10/μL (IQR 4–19/μL), <em>p</em> = 0.050) and higher PLT on day 7 (143 × 10³/μL (IQR 103–168 × 10³/μL) vs. 105 × 10³/μL (IQR 68–141 × 10³/μL), <em>p</em> = 0.02), with higher ALC on day 14 (308/μL (IQR 171–530/μL) vs. 180/μL (IQR 93–317/μL), <em>p</em> = 0.016) and on day 21 (529/μL (IQR 240–610/μL) vs. 225/μL (IQR 121–328/μL), <em>p</em> &lt; 0.001). In univariate analysis, ACR was associated with higher BC on day 14 (<em>p</em> = 0.004), higher PLT on day 7 (p = 0.02), higher ALC on days 14 (<em>p</em> = 0.04) and 21 (p &lt; 0.001). Multivariable regression model showed the most significant association between higher BC on day 14 and ACR (<em>p</em> = 0.015).</div></div><div><h3>Conclusion</h3><div>Lower BC two weeks after rATG induction is associated with less ACR during the first post-HTx year.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102173"},"PeriodicalIF":1.6,"publicationDate":"2025-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of complement inhibitors against refractory antibody-mediated rejection of lung transplantation: Two clinical cases","authors":"Hadrien Mallet ,&nbsp;Laurent Razat ,&nbsp;Quentin Perrier ,&nbsp;Amandine Briault ,&nbsp;Christel Saint Raymond ,&nbsp;Loic Falque ,&nbsp;Lionel Rostaing ,&nbsp;Bruno Degano ,&nbsp;Pierrick Bedouch","doi":"10.1016/j.trim.2025.102174","DOIUrl":"10.1016/j.trim.2025.102174","url":null,"abstract":"<div><div>Antibody-mediated rejection (AMR) has been recognized as a significant cause of acute and chronic lung allograft dysfunction after lung transplantation. Some treatments, eculizumab, an anti-complement (C)5 component monoclonal antibody (Mab), seem to have a promising effect in the management of some patients with AMR. We present two patients with acute AMR after lung transplantation who received the anti-C5 Mab therapy. In both cases, we identified the presence of C4d deposition in the peritubular capillaries on trans-alveolar biopsies, which suggested activation of complement in AMR. Prior to eculizumab therapy, both patients had also received immunoadsorption, courses of intravenous immunoglobulins (IVIG) and rituximab. For the first patient, we have shown that eculizumab can serve as an effective bridge to re-transplantation. For the second patient, we observed the absence of clinical and biological efficacy, and without a clear therapeutic efficacy the therapy with eculizumab had been discontinued after two months.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"89 ","pages":"Article 102174"},"PeriodicalIF":1.6,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}