Matthew McGuirk, Moazzam Shahzad, Muhammad Kashif Amin, Muhammad Atif Khan, Polina Bellman, Dinesh Pal Mudaranthakam, Shaun DeJarnette, Forat Lutfi, Nausheen Ahmed, Rajat Bansal, Haitham Abdelhakim, Chelsea Gorsline, Dennis Matthew Shoemaker, Al-Ola Abdallah, Leyla Shune, Sunil H. Abhyankar, Anurag K. Singh, Joseph P. McGuirk, Muhammad Umair Mushtaq
{"title":"Predictors of cytomegalovirus reactivation after allogeneic hematopoietic cell transplantation: Insights from a real-world experience","authors":"Matthew McGuirk, Moazzam Shahzad, Muhammad Kashif Amin, Muhammad Atif Khan, Polina Bellman, Dinesh Pal Mudaranthakam, Shaun DeJarnette, Forat Lutfi, Nausheen Ahmed, Rajat Bansal, Haitham Abdelhakim, Chelsea Gorsline, Dennis Matthew Shoemaker, Al-Ola Abdallah, Leyla Shune, Sunil H. Abhyankar, Anurag K. Singh, Joseph P. McGuirk, Muhammad Umair Mushtaq","doi":"10.1016/j.trim.2024.102039","DOIUrl":"10.1016/j.trim.2024.102039","url":null,"abstract":"<div><h3>Background</h3><p>We aimed to investigate factors associated with cytomegalovirus (CMV) viremia and CMV disease and its impact on post-transplant outcomes including overall survival (OS) following allogeneic hematopoietic stem cell transplantation (Allo-SCT).</p></div><div><h3>Methods</h3><p>We conducted a single-center retrospective study including 452 Allo-SCT recipients (matched unrelated donor, MUD 61%; haploidentical, haplo 39%) from 2016 to 2021. Data were analyzed using SPSS v28. Descriptive (chi-square and <em>t</em>-test), Kaplan-Meier and regression analyses were conducted.</p></div><div><h3>Results</h3><p>The median age was 57 years. Sixty-one percent were males and 84.3% were Caucasians. CMV serostatus was positive in 59.1% of recipients. The median follow-up was 24.4 months. CMV viremia and CMV disease were observed in 181 (40%) and 32 (7%) patients, respectively. Among CMV seropositive recipients, 65% developed CMV viremia and 11% were noted to have CMV disease compared to 4% and 1% in seronegative recipients, respectively (<em>p</em> < 0.001). Patients with CMV disease had significantly lower OS than those without CMV disease (median 14.1 months vs. not reached, <em>p</em> = 0.024); however, OS was not associated with CMV viremia (median not reached in both groups, <em>p</em> = 0.640). Letermovir prophylaxis was used in 66% (<em>n</em> = 176/267) of CMV seropositive recipients, but no impact was observed on the incidence of CMV viremia or CMV disease and OS.</p></div><div><h3>Conclusions</h3><p>CMV disease leads to significantly inferior survival after an allogeneic hematopoietic cell transplantation. Recipient CMV seropositive status was associated with the risk of CMV viremia and CMV disease, and this was not abrogated with the use of Letermovir prophylaxis.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102039"},"PeriodicalIF":1.5,"publicationDate":"2024-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000558/pdfft?md5=a4c72fed33a36edcef0a7d9ef43be792&pid=1-s2.0-S0966327424000558-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140185656","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}
Sudha Kodali , Constance M. Mobley , Elizabeth W. Brombosz , Analisa Lopez , Riki Graves , John Ontiveros , Marcela Velazquez , Ashish Saharia , Yee Lee Cheah , Caroline J. Simon , Christian Valverde , Alphonse Brown , Julie Corkrean , Linda W. Moore , Edward A. Graviss , David W. Victor III , Kelly Maresh , Mark J. Hobeika , Chukwuma Egwim , R. Mark Ghobrial
{"title":"Effect of a Hispanic outreach program on referral and liver transplantation volume at a single center","authors":"Sudha Kodali , Constance M. Mobley , Elizabeth W. Brombosz , Analisa Lopez , Riki Graves , John Ontiveros , Marcela Velazquez , Ashish Saharia , Yee Lee Cheah , Caroline J. Simon , Christian Valverde , Alphonse Brown , Julie Corkrean , Linda W. Moore , Edward A. Graviss , David W. Victor III , Kelly Maresh , Mark J. Hobeika , Chukwuma Egwim , R. Mark Ghobrial","doi":"10.1016/j.trim.2024.102034","DOIUrl":"10.1016/j.trim.2024.102034","url":null,"abstract":"<div><h3>Background</h3><p>Although Hispanic patients have high rates of end-stage liver disease and liver cancer, for which liver transplantation (LT) offers the best long-term outcomes, they are less likely to receive LT. Studies of end-stage renal disease patients and kidney transplant candidates have shown that targeted, culturally relevant interventions can increase the likelihood of Hispanic patients receiving kidney transplant. However, similar interventions remain largely unstudied in potential LT candidates.</p></div><div><h3>Methods</h3><p>Referrals to a single center in Texas with a large Hispanic patient population were compared before (01/2018–12/2019) and after (7/2021–6/2023) the implementation of a targeted outreach program. Patient progress toward LT, reasons for ineligibility, and differences in insurance were examined between the two eras.</p></div><div><h3>Results</h3><p>A greater proportion of Hispanic patients were referred for LT after the implementation of the outreach program (23.2% vs 26.2%, <em>p</em> = 0.004). Comparing the pre-outreach era to the post-outreach era, more Hispanic patients achieved waitlisting status (61 vs 78, respectively) and received a LT (971 vs 82, respectively). However, the proportion of Hispanic patients undergoing LT dropped from 30.2% to 20.3%. In the post-outreach era, half of the Hispanic patients were unable to get LT for financial reasons (112, 50.5%).</p></div><div><h3>Conclusions</h3><p>A targeted outreach program for Hispanic patients with end-stage liver disease effectively increased the total number of Hispanic LT referrals and recipients. However, many of the patients who were referred were ineligible for LT, most frequently for financial reasons. These results highlight the need for additional research into the most effective ways to ameliorate financial barriers to LT in this high-need community.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102034"},"PeriodicalIF":1.5,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159122","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":"Bioinformatics analysis characterizes immune infiltration landscape and identifies potential blood biomarkers for heart transplantation","authors":"Yujia Wang , Xiaoping Peng","doi":"10.1016/j.trim.2024.102036","DOIUrl":"10.1016/j.trim.2024.102036","url":null,"abstract":"<div><p>Background: Cardiac allograft rejection (AR) remains a significant complication following heart transplantation. The primary objective of our study is to gain a comprehensive understanding of the fundamental mechanisms involved in AR and identify possible therapeutic targets.</p><p>Methods: We acquired the <span>GSE87301</span><svg><path></path></svg> dataset from the Gene Expression Omnibus database. In <span>GSE87301</span><svg><path></path></svg>, a comparison was conducted on blood samples from patients with and without cardiac allograft rejection (AR and NAR) to detect differentially expressed genes (DEGs). Enrichment analysis was conducted to identify the pathways that show significant enrichment during AR. Machine learning techniques, including the least absolute shrinkage and selection operator regression (LASSO) and random forest (RF) algorithms, were employed to identify potential genes for the diagnosis of AR. The diagnostic value was evaluated using a nomogram and receiver operating characteristic (ROC) curve. Additionally, immune cell infiltration was analyzed to explore any dysregulation of immune cells in AR.</p><p>Results: A total of 114 DEGs were identified from the <span>GSE87301</span><svg><path></path></svg> dataset. These DEGs were mainly found to be enriched in pathways related to the immune system. To identify the signature genes, the LASSO and RF algorithms were used, and four genes, namely <em>ALAS2</em>, <em>HBD</em>, <em>EPB42</em>, and <em>FECH</em>, were identified. The performance of these signature genes was evaluated using the receiver operating characteristic curve (ROC) analysis, which showed that the area under the curve (AUC) values for <em>ALAS2</em>, <em>HBD</em>, <em>EPB42</em>, and <em>FECH</em> were 0.906, 0.881, 0.900, and 0.856, respectively. These findings were further confirmed in the independent datasets and clinical samples. The selection of these specific genes was made to construct a nomogram, which demonstrated excellent diagnostic ability. Additionally, the results of the single-sample gene set enrichment analysis (ssGSEA) revealed that these genes may be involved in immune cell infiltration.</p><p>Conclusion: We identified four signature genes (<em>ALAS2</em>, <em>HBD</em>, <em>EPB42</em>, and <em>FECH</em>) as potential peripheral blood diagnostic candidates for AR diagnosis. Additionally, a nomogram was constructed to aid in the diagnosis of heart transplantation. This study offers valuable insights into the identification of candidate genes for heart transplantation using peripheral blood samples.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102036"},"PeriodicalIF":1.5,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159121","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":"Efficacy and safety of cladribine in combination with busulfan and cyclophosphamide as an intensive conditioning regimen preceding allogeneic hematopoietic stem cell transplantation in relapsed or refractory acute myeloid leukemia","authors":"Fang Xiao , Huanxu Guo , Xueqian Yan, Meiying Qi, Jingyi Zhang","doi":"10.1016/j.trim.2024.102037","DOIUrl":"10.1016/j.trim.2024.102037","url":null,"abstract":"<div><h3>Background</h3><p>Cladribine, an analogue of deoxyadenosine, is used for therapy of hematological malignancies. Cladribine-containing regimen has been recommended as a rescue therapy for relapsed or refractory (R/R) acute myeloid leukemia (AML). Its combination with busulfan plus cyclophosphamide (BuCy), as an intensive conditioning regimen prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT), requires more clinical evidence. This study aimed to explore the efficacy and safety of cladribine plus BuCy administered as an intensive conditioning regimen before allo-HSCT in R/R AML patients.</p></div><div><h3>Methods</h3><p>Twenty-three R/R AML patients, who underwent cladribine plus BuCy intensive conditioning regimen before allo-HSCT, were retrospectively analyzed. The median (range) follow-up duration time of observation was 0.73 (0.08–2.69) years.</p></div><div><h3>Results</h3><p>The median (range) returned levels of mononuclear cells were 11.5 (6.1–18.5) x 108/kg and CD34+ cells were 5.5 (3.5–9.3) x 106/kg. The median (range) time of platelet reconstitution was 13.0 (9.0–21.0) days and neutrophil reconstitution was 14.0 (11.0–26.0) days. The incidence of conditioning regimen related toxicity (CRRT) affected 69.6% of patients; all CRRT-affected patients had grade I-II symptoms, including gastrointestinal tract (39.1%), oral cavity (26.1%), liver (8.7%), and kidney (4.3%) CRRTs. The incidence of acute graft-versus-host disease (GVDH) included 30.4% among all patients with 4.3% of grade III-IV acute GVHD, and 34.8% of chronic GVHD. During the follow-up period, 4 (17.4%) patients relapsed, and 6 (26.1%) patients died (cause of death: disease relapse, <em>n</em> = 3; infection, <em>n</em> = 2; GVHD, <em>n</em> = 1). The 1-year and 2-year accumulating event-free survival rates were 66.3% and 53.1%, respectively. The 1-year accumulating overall survival rate was 74.7% and 2-year survival rate was 64.0%.</p></div><div><h3>Conclusion</h3><p>Cladribine plus BuCy intensive conditioning regimen before allo-HSCT exhibits favorable treatment efficacy with acceptable toxicity in R/R AML patients.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102037"},"PeriodicalIF":1.5,"publicationDate":"2024-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000534/pdfft?md5=914ca45c10b04e3388d5aecf6d0df6a7&pid=1-s2.0-S0966327424000534-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159123","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}
Lidan Zhang , Ge Kuang , Xia Gong , Rui Huang , Zizuo Zhao , Yan Li , Jingyuan Wan , Bin Wang
{"title":"Piperine attenuates hepatic ischemia/reperfusion injury via suppressing the TLR4 signaling cascade in mice","authors":"Lidan Zhang , Ge Kuang , Xia Gong , Rui Huang , Zizuo Zhao , Yan Li , Jingyuan Wan , Bin Wang","doi":"10.1016/j.trim.2024.102033","DOIUrl":"10.1016/j.trim.2024.102033","url":null,"abstract":"<div><p>Piperine, the major active substance in black pepper, has been shown to have anti-inflammatory and antioxidant effects in several ischemic diseases. However, the role of piperine in hepatic ischemia/reperfusion injury (HIRI) and its underlying mechanisms remain unclear. In this study, the mice were administered piperine (30 mg/kg) intragastric administration before surgery. After 24 h of hepatic ischemia-reperfusion, liver histopathological evaluation, serum transaminase measurements, and TUNEL analysis were performed. The infiltration of inflammatory cells and production of inflammatory mediators in the liver tissue were determined by immunofluorescence and immunohistochemical staining. The protein levels of toll-like receptor 4 (TLR4) and related proteins such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), p65, and p38 were detected by western blotting. The results showed that plasma aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte apoptosis, oxidative stress, and inflammatory cell infiltration significantly increased in HIRI mice. Piperine pretreatment notably repaired liver function, improved the histopathology and apoptosis of liver cells, alleviated oxidative stress injury, and reduced inflammatory cell infiltration. Further analysis showed that piperine attenuated tumor necrosis factor-a (TNF-α) and interleukin 6 (IL-6) production and reduced TLR4 activation and phosphorylation of IRAK1, p38, and NF-κB in HIRI. Piperine has a protective effect against HIRI through the TLR4/IRAK1/NF-κB signaling pathway and may be a safer option for future clinical treatment and prevention of ischemia-related diseases.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102033"},"PeriodicalIF":1.5,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140132662","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":"Risks of infection and severity of coronavirus disease 2019 in kidney transplant recipients: A single-center cohort study","authors":"Kuniaki Inoue , Shunta Hori , Mitsuru Tomizawa , Tatsuo Yoneda , Yasushi Nakai , Makito Miyake , Nobumichi Tanaka , Kiyohide Fujimoto","doi":"10.1016/j.trim.2024.102023","DOIUrl":"10.1016/j.trim.2024.102023","url":null,"abstract":"<div><h3>Background</h3><p>The severity of coronavirus disease 2019 (COVID-19) is known to be high in kidney transplant recipients; however, the risk factors for COVID-19 infection in these patients has not been studied extensively. Therefore, we explored the predictors of COVID-19 infection and severity in kidney transplant recipients in Japan.</p></div><div><h3>Methods</h3><p>This study included kidney transplant recipients who were regularly followed-up at our hospital from February 2021 to March 2023. We retrospectively reviewed the patients' medical charts; obtained their clinical information, including comorbidities, immunosuppressant usage, and presence of COVID-19 infection; and assessed the risk of COVID-19 infection and severity. Severe illness was defined as a decrease in oxygen saturation.</p></div><div><h3>Results</h3><p>Among the 155 patients, 50 (32.3%) were infected with COVID-19. Multivariate analysis revealed that recipients taking >5 mg of prednisolone or taking tacrolimus instead of cyclosporine were at higher risk of infection (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.01–5.40; OR 2.29, 95% CI 1.03–5.07, respectively). Furthermore, of the 50 infected recipients, 42 had minor illness and eight had severe illness. Multivariate analysis revealed that recipients taking >5 mg of prednisolone were at a higher risk of severity (OR, 11.60, 95% CI 1.19–113.00).</p></div><div><h3>Conclusion</h3><p>In kidney transplant recipients, the infection rate and severity of COVID-19 tended to increase with higher maintenance doses of steroids. Recipients taking >5 mg of prednisolone should be considered a switch from tacrolimus to cyclosporine because cyclosporine may inhibit viral replication and reduce the risk of infection.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102023"},"PeriodicalIF":1.5,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060634","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}
Yue Xu , Yuxuan Wang , Di Zhang , Hao Zhang , Yicun Wang , Wei Wang , Xiaopeng Hu
{"title":"An autophagy-associated diagnostic signature based on peripheral blood for antibody-mediated rejection in renal transplantation","authors":"Yue Xu , Yuxuan Wang , Di Zhang , Hao Zhang , Yicun Wang , Wei Wang , Xiaopeng Hu","doi":"10.1016/j.trim.2024.102021","DOIUrl":"10.1016/j.trim.2024.102021","url":null,"abstract":"<div><h3>Background</h3><p>Antibody-mediated rejection (ABMR) emerged as a major cause of graft loss in renal transplantation. Needle biopsy is the gold standard for diagnosis of ABMR in renal allografts. Thus, noninvasive diagnosis methods of ABMR with high accuracy are urgently needed to prevent unnecessary biopsies.</p></div><div><h3>Methods</h3><p>We collected peripheral blood transcriptome data from two independent renal transplantation cohorts with patients with ABMR, stable well-functioning transplants (STA), and T-cell mediated rejection (TCMR). Differentially expressed genes (DEGs) were identified by comparing the ABMR group with the STA group. In addition, functional enrichment analysis and gene set enrichment analysis were performed to seek new key underlying mechanisms in ABMR. Subsequently, we utilized a Boruta algorithm and least absolute shrinkage and selection operator logistic algorithm to establish a diagnostic model which was then evaluated and validated in an independent cohort.</p></div><div><h3>Results</h3><p>According to functional enrichment analysis, autophagy was found to be the primary upregulated biological process in ABMR. Based on algorithms, three autophagy-associated genes, ubiquitin specific peptidase 33 (USP33), Ras homolog mTORC1 binding (RHEB), and ABL proto-oncogene 2 (ABL2), were selected to establish the diagnostic model in the training cohort. This autophagy-related gene model possessed good diagnostic value in distinguishing ABMR from STA blood samples in the training cohort (AUC = 0.907) and in the validation cohort (AUC = 0.972). In addition, this model also showed good discernibility in distinguishing ABMR from TCMR in the training and validation cohorts (AUCs = 0.908 and 0.833).</p></div><div><h3>Conclusion</h3><p>We identified and validated an autophagy-associated diagnostic model with high accuracy for renal transplant patients with ABMR. Our study provided a new potential test for the non-invasive diagnosis of ABMR in clinical practice and highlighted the importance of autophagy in ABMR.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102021"},"PeriodicalIF":1.5,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060596","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":"The hybrid CL-SP-D molecule has the potential to regulate xenogeneic rejection by human neutrophils more efficiently than CD47","authors":"Keigo Iemitsu , Rieko Sakai , Akira Maeda , Katarzyna Gadomska , Shuhei Kogata , Daiki Yasufuku , Jun Matsui , Kazunori Masahata , Masafumi Kamiyama , Hiroshi Eguchi , Soichi Matsumura , Yoichi Kakuta , Hiroshi Nagashima , Hiroomi Okuyama , Shuji Miyagawa","doi":"10.1016/j.trim.2024.102020","DOIUrl":"10.1016/j.trim.2024.102020","url":null,"abstract":"<div><h3>Objective</h3><p>Innate immunity plays a vital role in xenotransplantation. A CD47 molecule, binding to the SIRPα expressed on monocyte/macrophage cells, can suppress cytotoxicity. Particularly, the SIRPα contains ITIM, which delivers a negative signal. Our previous study demonstrated that the binding between CL-P1 and surfactant protein-D hybrid (CL-SP-D) with SIRPα regulates macrophages' phagocytic activity. In this study, we examined the effects of human CD47 and CL-SP-D expression on the inhibition of xenograft rejection by neutrophils in swine endothelial cells (SECs).</p></div><div><h3>Methods</h3><p>We first examined SIRPα expression on HL-60 cells, a neutrophil-like cell line, and neutrophils isolated from peripheral blood. CD47-expressing SECs or CL-SP-D-expressing SECs were generated through plasmid transfection. Subsequently, these SECs were co-cultured with HL-60 cells or neutrophils. After co-culture, the degree of cytotoxicity was calculated using the WST-8 assay. The suppressive function of CL-SP-D on neutrophils was subsequently examined, and the results were compared with those of CD47 using naïve SECs as controls. Additionally, we assessed ROS production and neutrophil NETosis.</p></div><div><h3>Results</h3><p>In initial experiments, the expression of SIRPα on HL-60 and neutrophils was confirmed. Exposure to CL-SP-D significantly suppressed the cytotoxicity in HL-60 (<em>p</em> = 0.0038) and neutrophils (<em>p</em> = 0.00003). Furthermore, engagement with CD47 showed a suppressive effect on neutrophils obtained from peripheral blood (<em>p</em> = 0.0236) but not on HL-60 (<em>p</em> = 0.4244). The results of the ROS assays also indicated a significant downregulation of SEC by CD47 (<em>p</em> = 0.0077) or CL-SP-D (<em>p</em> = 0.0018). Additionally, the suppression of NETosis was confirmed (<em>p</em> = 0.0125) in neutrophils co-cultured with S/CL-SP-D.</p></div><div><h3>Conclusion</h3><p>These results indicate that CL-SP-D is highly effective on neutrophils in xenogeneic rejection. Furthermore, CL-SP-D was more effective than CD47 at inhibiting neutrophil-mediated xenograft rejection.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102020"},"PeriodicalIF":1.5,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060635","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}
Haoyuan Wang , Xin Mao , Yue Zhong , Xu Zhao , Chuntian Li , Jun Jiang , Zheng Hong , Nuoxin Wang , Feng Wang
{"title":"Human amniotic mesenchymal stem cells inhibit immune rejection injury from allogeneic mouse heart transplantation: A preliminary study on the microRNA expression","authors":"Haoyuan Wang , Xin Mao , Yue Zhong , Xu Zhao , Chuntian Li , Jun Jiang , Zheng Hong , Nuoxin Wang , Feng Wang","doi":"10.1016/j.trim.2024.102022","DOIUrl":"10.1016/j.trim.2024.102022","url":null,"abstract":"<div><h3>Background</h3><p>Mesenchymal stem cell therapy is a new treatment for immune rejection in heart transplantation. The aim of this paper is to investigate the effect of human amniotic mesenchymal stem cells (hAMSCs) on alleviating immune rejection of allogeneic heart transplantation in mice and its possible underlying mechanism.</p></div><div><h3>Methods</h3><p>We injected hAMSCs into cervical ectopic heart transplantation model mice via tail vein to observe the survival time, the pathological changes of donor myocardium, and the fluorescent distribution of hAMSCs after the transplantation. MicroRNAs (miRs) with significantly differential expression were obtained by RNA sequencing and bioinformatic analysis, and a dual luciferase reporter gene assay together with real-time quantitative PCR (qRT-PCR) was performed to verify the relationship between miRs and their targeting genes.</p></div><div><h3>Results</h3><p>The intervention of hAMSCs prolonged the graft survival time and alleviated the pathological damage of the donor heart. The injected hAMSCs were distributed mainly in the liver, spleen, and kidney, only a very small portion in the donor and recipient hearts. In the allogeneic transplantation models, the expression of miR-34b-5p significantly increased after hAMSC treatment. MiR-34b-5p showed a knockdown effect on gene <em>Fc gamma receptor 2B</em> (<em>FCGR2B</em>).</p></div><div><h3>Conclusions</h3><p>hAMSCs can reduce the immune rejection injury after allogeneic heart transplantation. This effect may be associated with the upregulation of miR-34b-5p expression to knock down its targeting gene <em>FCGR2B</em>.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102022"},"PeriodicalIF":1.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140060632","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}
Ana Flávia Vieira Ferreira de Assis , Letícia de Oliveira Santos , Mariana Almeida Botelho , Evaldo Nascimento , Raquel A. Fabreti-Oliveira
{"title":"Impact of COVID-19 vaccination on clinical outcomes in kidney transplant patients","authors":"Ana Flávia Vieira Ferreira de Assis , Letícia de Oliveira Santos , Mariana Almeida Botelho , Evaldo Nascimento , Raquel A. Fabreti-Oliveira","doi":"10.1016/j.trim.2024.102019","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102019","url":null,"abstract":"<div><h3>Introduction</h3><p>The global health crisis caused by the COVID-19 pandemic has resulted in severe mortality and morbidity. Immunosuppressed patients, such as kidney transplant recipients, are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.</p></div><div><h3>Objective</h3><p>The aim of this cohort study was to evaluate the impact of COVID-19 vaccination on clinical outcomes in patients with kidney transplants.</p></div><div><h3>Materials and methods</h3><p>In this retrospective study, 254 patients with kidney transplants were vaccinated against SARS-CoV-2 and a fraction of these contracted COVID-19. The diagnosis of COVID-19 was carried out by reverse transcriptase-polymerase chain reaction testing, and the patients received treatment involving immunosuppressive and COVID-19-specific protocols.</p></div><div><h3>Results</h3><p>SARS-CoV-2 infection was diagnosed in 38 (14.96%) patients before the COVID-19 vaccine was administered. After vaccination, an additional 29 (11.42%) patients were diagnosed with COVID-19. Risk factors for hospitalization included age, body mass index (BMI), comorbidities, and time elapsed since renal transplantation (<em>p</em> = 0.025, 0.038, 0.012, and 0.046, respectively). COVID-19 vaccination resulted in a significant decrease in the rate of hospital-acquired SARS-CoV-2 infection from 63.16% to 34.48% (<em>p</em> = 0.020). The proportion of patients from this cohort placed in intensive care units decreased from 23.68% to zero. Allograft rejections exhibited a decreasing trend from 13.16% to 6.90% (<em>p</em> = 0.690). This patient cohort displayed 15.79% mortality prior to COVID-19 vaccination that was reduced to nil after immunization.</p></div><div><h3>Conclusion</h3><p>COVID-19 vaccination significantly reduced COVID-19 severity and mortality in this cohort of patients with kidney transplants. The risk factors for hospitalization were determined to be age, BMI, comorbidities, and time since renal transplantation. COVID-19 vaccination resulted in a clinical outcome of reduced hospitalization and a decrease in clinical complications. The COVID-19 vaccination-derived adverse effects in this cohort were found to be comparable to those in the immunocompetent population.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102019"},"PeriodicalIF":1.5,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140041671","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}