Transplant immunology最新文献

{"title":"Glutamine supplementation improves the activity and immunosuppressive action of induced regulatory T cells in vitro and in vivo","authors":"Li Zhang ,&nbsp;Zhongya Xu ,&nbsp;Yuanjiu Li ,&nbsp;Ke-jia Wu ,&nbsp;Chongyuan Yu ,&nbsp;Wenjie Zhu ,&nbsp;Dong-lin Sun ,&nbsp;Li Zhu ,&nbsp;Jun Zhou","doi":"10.1016/j.trim.2024.102044","DOIUrl":"10.1016/j.trim.2024.102044","url":null,"abstract":"<div><h3>Background</h3><p>Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs).</p></div><div><h3>Methods</h3><p>CD4⁺CD45RA⁺T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-<em>versus</em>-host disease (GVHD) model was constructed to confirm the efficacy of glutamine-treated iTregs <em>in vivo</em>.</p></div><div><h3>Results</h3><p>After being cultured <em>in vitro</em>, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-β, and Ki67 (CTLA-4, IL-10, TGF-β are immunosuppressive markers of iTregs) compared with that of the control iTregs (<em>P</em> &lt; 0.05). Furthermore, the growth curve showed that the proliferative ability of glutamine-treated iTregs was better than that of the control iTregs (<em>P</em> &lt; 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (<em>P</em> &lt; 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (<em>P</em> &lt; 0.05). However, GPNA significantly reversed the effects of glutamine (<em>P</em> &lt; 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury.</p></div><div><h3>Conclusion</h3><p>Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102044"},"PeriodicalIF":1.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000601/pdfft?md5=b00b7c3f557e49bedfdf53c55596bd8f&pid=1-s2.0-S0966327424000601-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140791810","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":"Early recovery of natural killer cells post T-cell depleted allogeneic stem cell transplantation using alemtuzumab “in the bag”","authors":"Glenda M. Davison ,&nbsp;Jessica J. Opie ,&nbsp;Saarah F.G. Davids ,&nbsp;Rygana Mohammed ,&nbsp;Nicolas Novitzky","doi":"10.1016/j.trim.2024.102045","DOIUrl":"10.1016/j.trim.2024.102045","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;p&gt;Allogeneic stem cell transplantation (SCT) is a critical therapy for haematological malignancy but may lead to acute and chronic graft &lt;em&gt;versus&lt;/em&gt; host disease (GvHD). T-cell depletion with alemtuzumab, either &lt;em&gt;in vivo&lt;/em&gt; or &lt;em&gt;ex vivo,&lt;/em&gt; reduces the incidence of GvHD but is a risk factor for disease relapse and poor immune reconstitution. Natural killer (NK) cells are the first lymphocytes to recover. Classical NK cells make up &gt;90% of the normal circulating population and can directly kill neoplastic or virally infected cells while the regulatory subset makes up &lt;10%, secretes cytokines and is not cytotoxic. The recovery and balance of these subsets post SCT remains controversial, with most studies analysing patients who received unmanipulated grafts and &lt;em&gt;in vivo&lt;/em&gt; immunosuppression.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;p&gt;The aim was to assess the early recovery of NK cells in 18 consecutive patients receiving &lt;em&gt;ex vivo&lt;/em&gt; T-cell depleted SCT and to compare the results to 25 individuals receiving haploidentical non-T cell depleted grafts.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;All patients received myeloablative conditioning. After stem cell collection, the stem cells of the T cell depleted group were treated “in the bag” with alemtuzumab (CAMPATH 1H) at a concentration of 1&lt;!--&gt; &lt;!--&gt;mg/10&lt;sup&gt;8&lt;/sup&gt; mononuclear cells and thereafter immediately infused. For those receiving non-T cell depleted grafts, GvHD prophylaxis was with post infusion therapeutic doses of cyclophosphamide. Blood samples were collected at days 21, 28 and 90. Complete blood counts were performed on an automated analyser while lymphocyte and NK subsets were examined using multiparameter flowcytometry. NK cells were defined as lymphocytes which were CD3-/CD56+. The classical subset was recognised as CD56&lt;sup&gt;dim&lt;/sup&gt;/CD16+ while the regulatory population as CD56&lt;sup&gt;bright&lt;/sup&gt;/CD16-. The results for both transplant types were compared at all time points using SPSS v8 statistical software.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;The recovery of lymphocytes was slow in both groups. Those receiving non-T cell depleted grafts had significantly higher T cell counts at day 21 and 28 when compared to the T cell depleted group (&lt;em&gt;P&lt;/em&gt; &lt; 0.05). In contrast, NK cells in the &lt;em&gt;ex vivo&lt;/em&gt; T-cell depleted patients recovered rapidly and by day 21 was no different to normal (&lt;em&gt;p&lt;/em&gt; &gt; 0.05), while the non-T cell depleted group had significantly decreased numbers (&lt;em&gt;p&lt;/em&gt; &lt; 0.001), only recovering at day 90. Both groups had abnormal NK cell subset ratios with significantly elevated percentages of regulatory cells (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). However, significant differences were observed between the two groups with those receiving T cell depleted grafts having lower percentages of regulatory cells as well as higher numbers of classical NK cells at day 21 and 28 (&lt;em&gt;p&lt;/em&gt; &lt; 0.01).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;p&gt;This study ","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102045"},"PeriodicalIF":1.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000613/pdfft?md5=8f96b1e1839ab652893041087250fc3f&pid=1-s2.0-S0966327424000613-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140764911","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":"Borderline rejection: To treat or not to treat?","authors":"Alessandra Palmisano ,&nbsp;Marta D'Angelo ,&nbsp;Ilaria Gandolfini ,&nbsp;Marco Delsante ,&nbsp;Giovanni Maria Rossi ,&nbsp;Micaela Gentile ,&nbsp;Enrico Fiaccadori ,&nbsp;Paolo Cravedi ,&nbsp;Umberto Maggiore","doi":"10.1016/j.trim.2024.102047","DOIUrl":"10.1016/j.trim.2024.102047","url":null,"abstract":"<div><h3>Introduction</h3><p>It is unclear whether kidney transplant recipients with a biopsy diagnosis as a “borderline” acute T-cell mediated rejection (TCMR) requires the treatment with intravenous (iv) steroids pulse plus/minus intensification of the maintenance therapy (TRT) in comparison with the simple clinical follow-up (F-UP).</p></div><div><h3>Methods</h3><p>We retrospectively followed a consecutive series of kidney transplant recipients diagnosed with a borderline acute TCMR at biopsy by surveillance or clinical indication for 12 months and compared TRT and F-UP groups. We evaluated trends in renal function by measuring estimated glomerular filtration rate (eGFR) using multiple regression models. Repeated eGFR measures (REML) were adjusted for potential confounding factors for 12 months. The difference in 12-month eGFR values were observed in the TRT vs F-UP groups, type of biopsy, as well as the surveillance vs. clinical outcomes.</p></div><div><h3>Results</h3><p>Out of 59 included patients, 37% of them were in the TRT group and remaining 63% in the F-UP group. As expected, the TRT group had, at the time of biopsy, lower eGFR value of 39.0 ml/min/m2 [16.5] in comparison to 49.6 [19.6] ml/min/m² in the F-UP group (<em>P</em> = 0.043), Similarly, the TRT group required more frequent clinical biopsies vs. F-UP group (68% vs. 32%; <em>P</em> = 0.014). However, the TRT group recovered kidney function reaching the eGFR values of the F-UP group at 12 months; the increase being significant only in patients who received indication biopsies (<em>P</em> &lt; 0.001). The estimated adjusted TRT effect on 12-month eGFR change after indication biopsy was improved by +15.8 ml/min/1.73m² (95%CI: +0.1 to +31.4 ml/min/1.73 m2; <em>P</em> = 0.048 by three-way interaction term) compared to the F-UP group.</p></div><div><h3>Conclusion</h3><p>Our preliminary study supports the indication for the treatment of acute borderline TCMR only in cases with biopsies performed by clinical indication.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102047"},"PeriodicalIF":1.5,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140756655","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":"Beyond prevention: Unveiling the benefits of triple vaccination on COVID-19 severity and resource utilization in solid organ transplant recipients","authors":"Jared R. Zhang ,&nbsp;John C. Johnson ,&nbsp;Richard G. Preble ,&nbsp;Muhammad Mujtaba ,&nbsp;A. Scott Lea ,&nbsp;Heather L. Stevenson ,&nbsp;Michael Kueht","doi":"10.1016/j.trim.2024.102048","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102048","url":null,"abstract":"<div><h3>Objective</h3><p>Despite the widespread reduction in COVID-19-related morbidity and mortality attributed to vaccination in the general population, vaccine efficacy in solid organ transplant recipients (SOTR) remains under-characterized. This study aimed to investigate clinically relevant outcomes on double and triple-vaccinated versus unvaccinated SOTR with COVID-19.</p></div><div><h3>Study design and setting</h3><p>A retrospective propensity score-matched cohort study was performed utilizing data from the US Collaborative Network Database within TriNetX (<em>n</em> = 117,905,631). We recruited vaccinated and unvaccinated (matched controls) SOTR with COVID-19 over two time periods to control for vaccine availability: December 2020 to October 2022 (bi-dose, double-dose vaccine effectiveness) and December 2020 to April 2023 (tri-dose, triple-dose vaccine effectiveness). A total of 42 factors associated with COVID-19 disease severity were controlled for including age, obesity, diabetes, and hypertension. We monitored 30-day outcomes including acute respiratory failure, intubation, and death following a diagnosis of COVID-19.</p></div><div><h3>Results</h3><p>Subjects were categorized into two cohorts based on the two time periods: bi-dose cohort (vaccinated, <em>n</em> = 462; unvaccinated, <em>n</em> = 20,998); tri-dose cohort (vaccinated, <em>n</em> = 517; unvaccinated, <em>n</em> = 23,061).Compared to unvaccinated SOTR, 30-day mortality was significantly lower for vaccinated subjects in both cohorts: tri-dose (2.0% vs 7.5%, HR = 0.22 [95% CI: 0.11, 0.46]); bi-dose (3.7% vs 8.2%, HR = 0.43 [95% CI: 0.24, 0.76]). Hospital admission rates were similar between bi-dose vaccinated and unvaccinated subjects (33.1% vs 28.6%, HR = 1.2 [95% CI: 0.95, 1.52]). In contrast, tri-dose vaccinated subjects had a significantly lower likelihood of hospital admission (29.4% vs 36.6%, HR = 0.74 [95% CI: 0.6, 0.91]). Intubation rates were significantly lower for triple-vaccinated- (2.3% vs 5.2%, <em>p</em> &lt; 0.05), but not double-vaccinated subjects (3.0% vs 5.2%, <em>p</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>In solid organ transplant recipients with COVID-19, triple vaccination, but not double vaccination, against SARS-CoV-2 was associated with significantly less hospital resource utilization, decreased disease severity, and fewer short-term complications. These real-world data from extensively matched controls support the protective effects of COVID-19 vaccination with boosters in this vulnerable population.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102048"},"PeriodicalIF":1.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140618624","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":"Clinico-epidemiological characteristics of early- versus late-onset cytomegalovirus disease among renal transplant recipients: A two-decade experience","authors":"Shuvam Roy ,&nbsp;Anupma Kaul ,&nbsp;Dharmendra Singh Bhadhuria ,&nbsp;Narayan Prasad ,&nbsp;Atul Garg ,&nbsp;Rungmei S.K. Marak ,&nbsp;Manas Ranjan Patel ,&nbsp;Manas Ranjan Behera ,&nbsp;Ravi Shankar Kushwaha ,&nbsp;Monika Yachha","doi":"10.1016/j.trim.2024.102040","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102040","url":null,"abstract":"<div><h3>Background</h3><p>Reactivation of cytomegalovirus (CMV) infection in transplant patients is high because of immunosuppression. We have evaluated the clinical and epidemiological characteristics of early versus late onset of CMV infection among renal transplant recipients.</p></div><div><h3>Methods</h3><p>A single center retrospective observational study was conducted among renal transplant recipients who underwent kidney transplant between January 2002 and December 2021. CMV disease was classified as early or late depending on its detection prior to or after 90 days post-transplantation. Herein, we reported the differences between early and late onset of CMV disease with respect to clinical symptoms, the use of immunosuppression and the impact on graft outcomes.</p></div><div><h3>Results</h3><p>Out of total 2164 renal transplant recipients, 156 patients (7.2%) were diagnosed with CMV disease. Among these 156 patients, 25 patients (16%) had early CMV while 131 patients (84%) had late CMV. Overall, the two groups did not differ with respect to the induction or maintenance of immunosuppressive agents. However, the proportion of CMV syndrome was greater among early (56.0%) than late (26.7%) CMV groups (<em>p</em> = 0.01). In contrast, tissue invasive disease was more frequent among late (73.3%) in comparison to early (44.0%) CMV groups (<em>p</em> = 0.01). Among clinical symptoms, diarrhea was more frequent in late (63.4%) vs. early (36%) CMV-affected patients (p = 0.01). Graft loss occurred in 4.0% of early CMV group vs. 25.2% of late CMV group (<em>p</em> = 0.03). Neither of the clinical groups differed with respect to occurrence of biopsy-proven allograft rejection post-infection.</p></div><div><h3>Conclusions</h3><p>Early CMV disease presents more frequently as CMV syndrome while late CMV disease usually manifests itself as tissue invasive disease. Graft loss is more common in patients with late onset of CMV disease.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102040"},"PeriodicalIF":1.5,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140351170","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":"Serum IL-6 predicts risk of kidney transplant failure independently of immunological risk","authors":"Julius Friedmann ,&nbsp;Antonia Schuster ,&nbsp;Simone Reichelt-Wurm ,&nbsp;Bernhard Banas ,&nbsp;Tobias Bergler ,&nbsp;Louisa Steines","doi":"10.1016/j.trim.2024.102043","DOIUrl":"10.1016/j.trim.2024.102043","url":null,"abstract":"<div><p>Interleukin-6 (IL-6) is an important immune mediator and a target for novel antibody therapies. In this study, we aimed to determine whether serum IL-6 levels are associated with immunological risk, allograft rejection and outcomes in kidney transplant (Ktx) patients. We retrospectively analyzed the data of 104 patients who underwent Ktx at our center between 2011 and 2015. The patients were divided into high- and low-risk groups (<em>n</em> = 52 per group) based on panel reactive antibody (PRA) percentage ≥ 35%, the existence of pre-Ktx donor-specific antibodies (DSA), or a previous transplant. IL-6 concentrations were measured before and at 3 months, 12 months, and 3 years after Ktx. Serum IL-6 levels tended to be higher in high-risk patients than in low-risk patients prior to Ktx and at 12 months after Ktx; however, the difference did not reach statistical significance (pre-Ktx, high-risk: 1.995 ± 2.79 pg/ml vs. low-risk: 1.43 ± 1.76 pg/ml, <em>p</em> = 0.051; 12 mo. high-risk: 1.16 ± 1.87 pg/ml vs. low-risk: 0.78 ± 1.13 pg/ml, <em>p</em> = 0.067). IL-6 levels were correlated with the types (no rejection, T cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), or both) and time (&lt;1 year vs. &gt;1 year after Ktx) of rejection, as well as patient and graft survival. Patients with both TCMR and ABMR had significantly higher IL-6 levels at 3 months (14.1 ± 25.2 pg/ml) than patients with ABMR (3.4 ± 4.8 pg/ml, <em>p</em> = 0.017), with TCMR (1.7 ± 1.3 pg/ml, <em>p</em> &lt; 0.001), and without rejection (1.7 ± 1.4 pg/ml, p &lt; 0.001). Three years after Ktx, patients with AMBR had significantly higher IL-6 levels (5.30 ± 7.66 pg/ml) than patients with TCMR (1.81 ± 1.61 pg/ml, <em>p</em> = 0.009) and patients without rejection (1.19 ± 0.95 pg/ml; <em>p</em> = 0.001). Moreover, three years after Ktx IL-6 levels were significantly higher in patients with late rejections (3.5 ± 5.4 pg/ml) than those without rejections (1.2 ± 1.0 pg/ml) (<em>p</em> = 0.006). The risk of death-censored graft failure was significantly increased in patients with elevated IL-6 levels at 12 months (IL-6 level &gt; 1.396 pg/ml, HR 4.61, <em>p</em> = 0.007) and 3 years (IL-6 level &gt; 1.976 pg/ml, HR 6.75, <em>p</em> = 0.003), but elevated IL-6 levels were not associated with a higher risk of death. Overall, our study highlights IL-6 as a risk factor for allograft failure and confirms that IL-6 levels are higher in patients developing ABMR compared to TCMR alone or no rejection.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102043"},"PeriodicalIF":1.5,"publicationDate":"2024-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140319273","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":"Circular RNA circEfnb2 promotes cell injury after cerebral infarction by sponging miR-202-5p and regulating TRAF3 expression","authors":"Limin Tu ,&nbsp;Wei Cheng ,&nbsp;Xudong Wang ,&nbsp;Zhixin Li ,&nbsp;Xing Li","doi":"10.1016/j.trim.2024.102042","DOIUrl":"10.1016/j.trim.2024.102042","url":null,"abstract":"<div><h3>Background</h3><p>Exogenous neural cell transplantation may be therapeutic for stroke, cerebral ischemic injury. Among other mechanisms, increasing findings indicated circular RNAs (circRNAs) regulate the pathogenesis progression of cerebral ischemia. Mmu_circ_0015034 (circEfnb2) was upregulated in focal cortical infarction established by middle cerebral artery occlusion (MCAO) in mice. Our study was designed to probe the molecular mechanism of circEfnb2 in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal damage in cerebral ischemia.</p></div><div><h3>Methods</h3><p>We established an in vitro OGD/R cell model. CircEfnb2 and microRNA-202-5p (miR-202-5p) levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). Lactate dehydrogenase (LDH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were assessed using specific kits. Tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β) levels were examined using an Enzyme-linked immunosorbent assay (ELISA). Flow cytometry analysis evaluated cell apoptosis. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved caspase 3, and Tumor necrosis factor receptor-associated factor 3 (TRAF3) were determined using Western blot assay.</p></div><div><h3>Results</h3><p>Overall, circEfnb2 was highly expressed whereas miR-202-5p was decreased in OGD/R-treated mouse hippocampal neuronal HT22 cells compared to normal controls (both <em>p</em> &gt; 0.05). From an in vitro functional perspective, circEfnb2 knockdown attenuated an OGD/R-triggered neuronal injury compared to controls (<em>p</em> &gt; 0.05). Mechanically, circEfnb2 acted as a sponge of miR-202-5p; downregulation of miR-202-5p annulled the inhibitory roles of circEfnb2 silencing in an OGD/R-caused neuronal injury model. Our analysis showed that miR-202-5p directly targeted TRAF3 as enhanced TRAF3 abolished the effects of miR-202-5p in the OGD/R-induced neuronal injury. In vivo, lentivirus with a short hairpin (sh)-circEfnb2 inhibited cerebral injury, when injected into cerebral cortex in MCAO mice (<em>p</em> &gt; 0.05).</p></div><div><h3>Conclusion</h3><p>Our results suggest that circEfnb2 deficiency may decrease OGD/R-induced HT22 cell damage by modulating the miR-202-5p/TRAF3 axis. This explanation may provide a new direction for cerebral infarction potential therapeutic targets.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102042"},"PeriodicalIF":1.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140289090","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":"Nocardiosis in kidney transplant recipients: A tertiary care center experience","authors":"Rungmei Marak ,&nbsp;Abdullah ,&nbsp;Manas Behera ,&nbsp;Anupma Kaul ,&nbsp;Dharmendra Bhadauria ,&nbsp;Narayan Prasad ,&nbsp;Manas Patel ,&nbsp;Ravi Kushwaha ,&nbsp;Monika Yachha","doi":"10.1016/j.trim.2024.102041","DOIUrl":"10.1016/j.trim.2024.102041","url":null,"abstract":"<div><h3>Introduction</h3><p>Kidney transplant recipients are at increased risk of opportunistic infections, including <em>Nocardia</em>. The incidence of nocardiosis in kidney transplant recipients is 0.4–1.3%. The data regarding its epidemiology and outcomes is limited.</p></div><div><h3>Methods</h3><p>This was a 10-year retrospective observational study from January 2012 to December 2021 at a tertiary care center in northern India, in which all kidney transplant recipients with <em>Nocardia</em> infection were included and followed.</p></div><div><h3>Results</h3><p>12 (1.1%) patients had a <em>Nocardia</em> infection among the 1108 kidney transplant recipients. All were living donor kidney transplant recipients, and the mean age at diagnosis was 48.67 ± 12.60 years. <em>Nocardia</em> infection occurred at a median of 26 months (range 4–235) post-transplantation, with 4 (33.1%) of the cases occurring within a year of transplant. Breakthrough infection occurred in 7 (58.3%) patients on cotrimoxazole prophylaxis. 41.7% (<em>n</em> = 5) cases had an episode of rejection in the preceding year of <em>Nocardia</em> diagnosis. Concurrent cytomegalovirus (CMV) infection was present in one (8.3%) case. The lung was the most frequently involved organ. Microscopy was positive in all the cases; while culture was positive in 10 cases, and antimicrobial susceptibility testing (AST) were performed for these isolates. The majority (60%) of isolates were resistant to cotrimoxazole. All tested isolates remained susceptible to Amikacin, Imipenem, and Linezolid. No patients experienced <em>Nocardia</em> recurrence after completion of antibiotic therapy. The mortality at 12 months was 66.7% (<em>n</em> = 4), and only one death was <em>Nocardia</em>-related.</p></div><div><h3>Conclusion</h3><p><em>Nocardia</em> may cause a late-manifesting infection beyond the traditional window. The cotrimoxazole prophylaxis may not be sufficient for <em>Nocardia</em> prevention.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102041"},"PeriodicalIF":1.5,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140307035","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 contribution of the donor vascularised hand and face allograft in transplant rejection: An immunological perspective","authors":"Kavit R. Amin ,&nbsp;James E. Fildes","doi":"10.1016/j.trim.2024.102035","DOIUrl":"10.1016/j.trim.2024.102035","url":null,"abstract":"<div><p>Overcoming immunological rejection remains a barrier to the safe adoption of Vascularised Composite Allotransplantation (VCA). To mitigate this risk, clinical protocols have been derived from solid organ transplantation, targeting recipient immunomodulation, yet VCA is unique. Face and hand composite allografts are composed of multiple different tissues, each with their own immunological properties.</p><p>Experimental work suggests that allografts carry variable numbers and populations of donor leukocytes in an organ specific manner. Ordinarily, these passenger leukocytes are transferred from the donor graft into the recipient circulation after transplantation. Whether alloantigen presentation manifests as acute allograft rejection or transplant tolerance is unknown. This review aims to characterise the immunological properties of the constituent parts of the donor face and hand, the potential fate of donor leukocytes and to consider theoretical graft specific interventions to mitigate early rejection.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102035"},"PeriodicalIF":1.5,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0966327424000510/pdfft?md5=31b5d063aa981337fbd6b0a59b6b595a&pid=1-s2.0-S0966327424000510-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140190175","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":"Prior cytomegalovirus reactivation may lead to worse bacterial bloodstream infection outcomes in HSCT patients","authors":"Shanshan Li ,&nbsp;Yang Xiao ,&nbsp;Mei Jia","doi":"10.1016/j.trim.2024.102038","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102038","url":null,"abstract":"<div><h3>Background</h3><p>Cytomegalovirus (CMV) reactivation is common after transplantation, and may further augment natural killer (NK) cell activity, which has a protective role through both innate and adaptive immune responses. Bacterial bloodstream infections (BBSIs) are a common cause of morbidity and mortality in patients following allo-HSCT. Therefore, we hypothesized that CMV reactivation might play a role in the outcomes of patients with BBSI after allo-HSCT.</p></div><div><h3>Objectives</h3><p>We investigated the role of CMV reactivation in the clinical outcomes of patients with BBSI after allo-HSCT.</p></div><div><h3>Study design</h3><p>A total of 101 BBSI patients (45 non-CMV reactivation [NCR] and 56 CMV reactivation [CR]) were included in the study following allo-HSCT. Clinical and laboratory findings were reviewed, and differences were tested using the Chi-square (<em>χ</em>^<em>2</em>) test. Multivariate Cox regression analysis was used to calculate hazard ratios for between-group comparisons of clinical outcomes.</p></div><div><h3>Results</h3><p>CMV reactivation had a negative prognostic impact on the clinical outcomes of BBSI patients following allo-HSCT with regard to the 1-year overall survival time (HR, 3.583; 95% CI, 1.347–9.533; <em>P</em> = 0.011). In 56 BBSI patients with CMV reactivation following allo-HSCT, the 1-year mortality among those in whom CMV was reactivated first (CRF) was significantly elevated (56.5% vs. 18.2%, <em>P</em> = 0.003) compared with patients in whom the BBSIs occurred first (BOF).</p></div><div><h3>Conclusions</h3><p>CMV reactivation in BBSI patients is related to higher mortality 1-year after allo-HSCT. Further studies on a larger cohort are needed to better understanding the mechanism of CMV reactivation influence.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"84 ","pages":"Article 102038"},"PeriodicalIF":1.5,"publicationDate":"2024-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140187696","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}