Transplant immunology最新文献

{"title":"Evaluation of new-onset BK viruria in post-renal transplant recipients by quantitative PCR.","authors":"Raza Ullah Asif, Eijaz Ghani, Muhammad Ali Rathore, Saadiya Mushtaq, Faraz Ahmed, Hammad Hussain","doi":"10.1016/j.trim.2024.102136","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102136","url":null,"abstract":"<p><strong>Background: </strong>The BK polyomavirus infection poses a substantial challenge for organ transplant recipients due to immunosuppression, resulting in BK virus-associated nephropathy (BKVAN) and a considerable risk of graft loss. Screening and prompt decrease of immunosuppression are essential for averting these consequences. We examined the frequency of BK viruria (viral load in urine) among post-renal transplant recipients, along with its association with age, viral load, and the timing of viral reactivation.</p><p><strong>Methods: </strong>The prospective cohort study was conducted at the Tertiary Care Hospital in Rawalpindi over a 12-month period, from January 1 to December 31, 2023. Urine specimens from 108 renal transplant recipients were collected and analysed for BK viruria every three months during the follow-up assessments. DNA extraction was performed using TANbead extractor, and amplification was carried out with Bio-Rad CFX-96 thermal cycler using Sacace TM amplification kit. Data was analysed using SPSS version 27.</p><p><strong>Results: </strong>In the cohort of 108 renal transplant recipients, BK viruria was detected in 16.7 % of cases. There was a higher prevalence of BK viruria in females (20 %) than males (16 %). The majority of positive cases were within the 41-60 years age group (61.1 %). Most of the patients (66.6 %) had viral loads below 1 million copies/mL. BK viruria was predominantly detected during the third quarter (between 7 and 9 months) post-transplant. The Chi-square test was applied between age and viral load, showing a significant association (p = 0.01). Similarly, gender and viral load also showed a significant relationship (p = 0.019).</p><p><strong>Conclusion: </strong>The study showed the frequency of 16.7 % of BK viruria in our small cohort after renal transplantation during the initial 12 months post-transplant. Age of recipients correlated with viral load and time of viral reactivation: middle-aged recipients had higher viral loads. BK viruria increased progressively over the initial nine months, with peak incidence in the third quarter post-transplant.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381726","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":"S100A9 regulates M1 macrophage polarization and exacerbates steatotic liver ischemia-reperfusion injury.","authors":"Mingwei Sheng, Weihua Liu, Zhangjiu Lu, Yuanbang Lin, Wenli Yu","doi":"10.1016/j.trim.2024.102134","DOIUrl":"https://doi.org/10.1016/j.trim.2024.102134","url":null,"abstract":"<p><strong>Objective: </strong>Steatotic livers exhibit higher susceptibility to ischemia reperfusion (IR) injury, which increase the risk of primary graft non-function following liver transplantation. S100A9 is identified as a pivotal innate immune sensor that regulates the progression of liver diseases. However, its significance in steatotic liver IR injury remains under-investigated.</p><p><strong>Methods: </strong>In mice model, we generated S100A9 knockout (S100A9 KO) mice to investigate the role of S100A9 in IR-stimulated steatotic livers. In vitro, primary bone marrow-derived macrophages were utilized to explore the effect of S100A9 in regulating macrophage polarization and inflammation.</p><p><strong>Results: </strong>S100A9 expression was markedly increased in steatotic livers of mice subjected to IR insult. S100A9 deletion significantly attenuated liver inflammatory injury, as evidenced by the diminished infiltration of both monocytes/macrophages and neutrophils (p < 0.05). The expression of proinflammatory factors was reduced (p < 0.05) at the same time. Additionally, S100A9-deficient livers demonstrated M1 polarization decrease and Toll-like receptor 4 (TLR4) suppression (p < 0.05). In vitro, genetic TLR4 inhibition led to nuclear factor kappa B (NF-κB) inactivation and subsequent M1 polarization decrease (p < 0.05) in macrophages treated with recombinant S100A9. Conclusion In this study, we highlight the pivotal role of TLR4/NF-κB as a critical mediator of S100A9 in inducing M1 macrophage polorization- dependent inflammation in steatotic livers IR injury.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378248","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 of Ruxolitinib with corticosteroids in idiopathic pneumonia syndrome post-allogeneic hematopoietic stem cell transplantation: A single-center experience and systematic review.","authors":"Moazzam Shahzad, Muhammad Atif Khan, Muhammad Kashif Amin, Zouina Sarfraz, Fizza Zulfiqar, Hana Qasim, Rajat Bansal, Kyle Brownback, Nausheen Ahmed, Sunil H Abhyankar, Joseph P McGuirk, Anurag K Singh, Muhammad Umair Mushtaq","doi":"10.1016/j.trim.2024.102135","DOIUrl":"10.1016/j.trim.2024.102135","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature.</p><p><strong>Methods: </strong>The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25.</p><p><strong>Results: </strong>The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero.</p><p><strong>Conclusion: </strong>The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378247","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 status of diversity in the heart transplant workforce.","authors":"Nasim Azizgolshani, David Blitzer, Monica Colvin, Hannah Copeland","doi":"10.1016/j.trim.2024.102097","DOIUrl":"10.1016/j.trim.2024.102097","url":null,"abstract":"<p><p>Cardiac surgery and cardiology consistently have the lowest representation of women and racial minorities among all the specialties. The poor representation of minorities and women in cardiology and cardiac surgery is compounded by the fact that heart failure risk continues to rise in the United States (US) and disproportionately affects non-white patients. Inclusion in academia is imperative in diversifying the workforce and in turn, in improving the care we provide to all of our patients.</p>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376095","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 prophylactic application of low-dose rabbit antithymocyte globulin in matched siblings HSCT with high-risk factors for graft-versus-host disease","authors":"","doi":"10.1016/j.trim.2024.102131","DOIUrl":"10.1016/j.trim.2024.102131","url":null,"abstract":"<div><div>Relapse and graft-versus-host disease (GVHD) are currently the predominant causes of mortality post allogeneic hematopoietic stem cell transplantation (allo-HSCT). The contentious use of antithymocyte globulin (ATG) for preventing GVHD in matched sibling HSCT scenarios has been a topic of significant debate. A retrospective analysis was conducted on matched sibling HSCT cases with high-risk factors for GVHD in our center from January 2018 to June 2023. Our assessment revealed that the group administered with ATG exhibited a 30 % incidence of acute GVHD (aGVHD), in contrast to 81.8 % in the non-ATG cohort (<em>P</em> = 0.037) among matched sibling HSCT cases with high GVHD risk factors. Furthermore, chronic GVHD (cGVHD) occurred in 20 % of the ATG group and 72.7 % of the non-ATG group (<em>P</em> = 0.03). Notably, the administration of ATG did not significantly impact disease relapse (<em>p</em> = 0.149), infection rates (<em>p</em> = 0.64), granulocyte recovery time (<em>p</em> = 0.15), platelet recovery time (<em>p</em> = 0.12), overall survival (<em>p</em> = 0.889), or disease-free survival time (<em>p</em> = 0.787). The use of rabbit antithymocyte globulin (r-ATG) at a 5 mg/kg dosage demonstrated a notable reduction in aGVHD and cGVHD incidences within sibling matched HSCT cases with high-risk factors for GVHD, without increasing rates of disease recurrence or infections. These findings highlight the potential benefit of using low-dose r-ATG in high-risk of GVHD sibling matched allogeneic HSCTs, although further validation with a larger cohort is necessary.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296303","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":"Structural social determinants of health as barriers to liver transplant waitlisting","authors":"","doi":"10.1016/j.trim.2024.102132","DOIUrl":"10.1016/j.trim.2024.102132","url":null,"abstract":"<div><div>Social determinants of health, both individual and structural, impact access to liver transplantation (LT). We aimed to evaluate the association between structural social determinants of health (SSDoH) and individual-level psychosocial factors (as measured by the Stanford Integrated Psychosocial Assessment for Transplant, SIPAT score) on failure to waitlist for LT. We conducted a single-center retrospective cohort study of 2762 patients evaluated for LT. SSDoH exposures included the Social Deprivation Index (SDI), the proportion of households on cash public assistance or supplemental nutrition assistance (% public assistance), and distance to the transplant center. Neighborhood SDI score in the highest quartile (OR 1.32, 95 % CI 1.07–1.63) and % on public assistance in the highest quartile (OR 1.41, 95 % CI 1.14–1.75) were associated with increased odds of not being waitlisted for LT. These associations remained significant after adjusting for individual psychosocial risk using SIPAT scores (≥21, high psychosocial risk). Highest quartile neighborhood SDI (OR 1.70, 95 % CI 1.13–2.54) and the highest quartile of % on public assistance (OR 1.67, 95 % CI 1.11–2.53) were also associated with increased odds of failure to waitlist for psychosocial reasons. However, these associations were no longer significant after adjusting for individual SIPAT scores. High-risk SIPAT scores were more prevalent in neighborhoods with the highest quartile of SSDoH measures. Transplant centers can design initiatives to build individual psychosocial support to mitigate the impact of structural barriers.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296302","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":"Post-transplantation monitoring and quantitation of microparticles in allogeneic hematopoietic cell transplantation","authors":"","doi":"10.1016/j.trim.2024.102133","DOIUrl":"10.1016/j.trim.2024.102133","url":null,"abstract":"<div><h3>Background</h3><div>Allogeneic hematopoietic stem cell transplantation (allo-HCT) represents a curative treatment for various blood-related disorders, including hematological malignancies and genetic disorders. The success of this procedure hinges on the efficacy of the conditioning regimen and the graft's ability to engraft and function properly. Microparticles (MPs), small vesicles produced from stimulated, apoptotic, or activated cells, are involved in both physiological and pathological processes. However, the impact of MPs on allo-HCT remains poorly understood.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the presence of MPs from different cell types in grafts and patient plasma after allo-HCT, as well as their association with various parameters. We measured MPs from CD34+, CD56+, CD3+, CD19+, and CD33+ cells in grafts and patient plasma from day 0 to day 60 after transplantation.</div></div><div><h3>Methods</h3><div>224 blood samples were collected from 19 consecutive allo –HCT recipients at 0, +4, +14,+30 and + 60 day as well as from their grafts. MPs isolated from the plasma and quantified by flow cytometry analysis.</div></div><div><h3>Results</h3><div>MP levels varied over time. Notably, CD34+ MP levels were linked to both early and late engraftment of neutrophils and platelets. Furthermore, grafts with high CD34+ and CD56+ MP levels in patient plasma on days 0 and + 4 were associated with late engraftment, whereas high CD33+ MP levels in both graft and patient plasma on day +4 were associated with early engraftment. Conditioning regimen affected CD19+ MP levels at day +14, and the number of CD34+, CD56+, and CD19+ MPs 30 days after transplantation was correlated with acute graft-versus-host disease.</div></div><div><h3>Conclusion</h3><div>These findings suggest that MPs derived from hematopoietic cells may play a significant role in the clinical course of patients following allo-HCT.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296301","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":"Combination of trimethoprim-sulfamethoxazole and mesenchymal stem cell therapy to treat toxoplasmic encephalitis after hematopoietic stem cell transplantation: A case report","authors":"","doi":"10.1016/j.trim.2024.102130","DOIUrl":"10.1016/j.trim.2024.102130","url":null,"abstract":"<div><p>Toxoplasmosis, caused by the parasite <em>Toxoplasma gondii</em>, is a life-threatening infection that may occur following hematopoietic stem cell transplantation (HSCT). Toxoplasmic encephalitis (TE) is one of the most severe manifestations of this infection and often results in unsatisfactory therapeutic outcomes, especially regarding neurological damage. Recent studies have demonstrated that human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) can significantly aid in neural repair and remodeling. Furthermore, hUC-MSCs have been shown to reduce the risk of graft-versus-host disease (GVHD) associated with the reduction or discontinuation of immunosuppressive therapy. In this case report, we present a pediatric patient who developed TE as a complication of haploidentical HSCT. The patient received a combined treatment regimen of standard anti-Toxoplasma therapy and adjunctive hUC-MSC therapy. The outcomes were satisfactory. The patient regained consciousness, maintained a stable body temperature, and regained the ability to perform daily activities independently. Additionally, next-generation sequencing revealed a decrease in Toxoplasma DNA sequences in the blood and cerebrospinal fluid to undetectable levels. This case report underscores the potential of hUC-MSCs as a promising therapeutic modality for TE.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243643","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":"Long-term CXCR3 antagonist AMG487 mitigated acute graft-versus-host disease by inhibiting T cell activation in a murine model","authors":"","doi":"10.1016/j.trim.2024.102128","DOIUrl":"10.1016/j.trim.2024.102128","url":null,"abstract":"<div><h3>Background</h3><p>Lymphocyte migration plays a key role in the development of acute graft-versus-host disease (aGVHD). Blocking lymphocyte migration by targeting chemokine receptors, such as CXCR3, may be a promising strategy for preventing and treating aGVHD. Our previous studies have shown that short-term CXCR3 antagonist treatment combined with cyclosporine A alleviated aGVHD. However, the effect of long-term AMG487 treatment on aGVHD survival has not been thoroughly investigated.</p></div><div><h3>Methods</h3><p>A murine aGVHD model was used to examine the expression of CXCR3 in donor T cells. The effects of short- and long-term AMG487 treatment on aGVHD survival were assessed. The infiltration of donor T cells into the liver and spleen tissues and the activation of donor T cells in splenic tissues were also examined.</p></div><div><h3>Results</h3><p>CXCR3 was consistently highly expressed in donor T cells in a murine aGVHD model. Long-term AMG487 treatment, but not short-term, improved survival and aGVHD outcomes (<em>p</em> &lt; 0.05). Furthermore, long-term AMG487 administration reduced the number of donor T cells in the liver but increased the number of donor T cells in the spleen (<em>p</em> &lt; 0.05). Long-term AMG487 treatment also inhibited donor T cell activation in the spleen (p &lt; 0.05).</p></div><div><h3>Conclusion</h3><p>This study demonstrates that long-term AMG487 treatment has a potential therapeutic effect on aGVHD and could be used as a novel therapy.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172667","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":"Smooth muscle cells clonally expand in a murine carotid allograft model complicated by immune reactions to reporter transgenes","authors":"","doi":"10.1016/j.trim.2024.102129","DOIUrl":"10.1016/j.trim.2024.102129","url":null,"abstract":"<div><h3>Background and aims</h3><p>Most experimental studies of allograft vasculopathy (AV) have relied on transplantation between major histocompatibility complex-mismatched inbred mouse strains, but this leads to the complete eradication of donor smooth muscle cells (SMCs) and lesions formed by recipient cells. This is unlike human AV which is thought to form mainly by donor SMCs. Here, we studied sources of neointimal cells in a minor histocompatibility antigen-mismatched AV model by combining male-to-female orthotopic carotid transplantations and lineage tracing by SMC-specific expression of fluorescent proteins.</p></div><div><h3>Methods</h3><p>To track SMC-derived cells in allograft vasculopathy, we used male donor mice with SMC-restricted Cre recombination of the mT/mG reporter transgene, which switches expression of membrane-bound red fluorescent protein (RFP) to green fluorescent protein (GFP), or the stochastically recombining Confetti reporter transgene, which yields a mosaic expression of four fluorescent proteins. Donor carotid segments were harvested and orthotopically allografted to female recipients that were wildtype or had non-recombined reporter transgenes. Inhibition of T cell responses by CTLA4Ig was used in some experiments. Sections of lesions harvested after 4 weeks were analyzed by fluorescence microscopy.</p></div><div><h3>Results</h3><p>Donor-derived SMCs survived and gave rise to part of the neointimal cells in experiments where carotid segments from recombined mT/mG male mice were transplanted into wild-type or non-recombined mT/mG female mice. Sex-mismatched transplants developed significant lesions, increasing the intimal and medial area 4.6-fold (<em>p</em> = 0.038) and 2.0-fold (<em>p</em> = 0.024) compared to sex- and fluorescence-matched controls, respectively. Interestingly, sex-matched fluorescence-positive transplants developed intimal lesions in 50% of fluorescence-naïve recipient controls. To study the clonal structure of the neointimal donor-derived SMC lineage cells, we then transplanted male carotids with heterozygous or homozygous recombined Confetti transgenes into female recipients. These transplants developed lesions with few surviving donor SMCs, indicating that expression of the Confetti reporter increased rejection and donor-specific SMC death. Some of the few remaining donor SMCs underwent clonal expansion. CTLA4Ig administration at the time of surgery did not improve SMC survival in mT/mG or Confetti transplants.</p></div><div><h3>Conclusion</h3><p>Male-to-female transplant models feature donor-derived SMCs, some of which undergo clonal expansion, but immune rejection to fluorescence reporters appears to bias results in lineage tracing models. Overcoming these challenges with alternative reporter transgenes or tolerant recipients is necessary to study the mechanisms by which donor SMCs contribute to allograft vasculopathy.</p></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S096632742400145X/pdfft?md5=c5cb82ddbbccc8cd674b0f491124b899&pid=1-s2.0-S096632742400145X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142172766","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}