De novo donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response.
Methods
Data of 105 adult living-donor KT recipients were retrospectively assessed.
Results
Of the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT.
Conclusions
PIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.
{"title":"Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients","authors":"Hiroaki Yamane, Kentaro Ide, Yuka Tanaka, Masahiro Ohira, Hiroyuki Tahara, Seiichi Shimizu, Hiroshi Sakai, Ryosuke Nakano, Hideki Ohdan","doi":"10.1016/j.trim.2024.102145","DOIUrl":"10.1016/j.trim.2024.102145","url":null,"abstract":"<div><h3>Background</h3><div><em>De novo</em> donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response.</div></div><div><h3>Methods</h3><div>Data of 105 adult living-donor KT recipients were retrospectively assessed.</div></div><div><h3>Results</h3><div>Of the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT.</div></div><div><h3>Conclusions</h3><div>PIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102145"},"PeriodicalIF":1.6,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584388","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}
Pub Date : 2024-11-02DOI: 10.1016/j.trim.2024.102144
Yu Wang , Tingting Lan , Shao-Hua Wu , Jiangong Ma , Xunfeng Zou
A new osmoprotectant-containing multiple saccharide (MS) solution was formulated for this study. The primary objectives were to compare the effects of the MS solution with those of the University of Wisconsin (UW) solution and hypertonic citrate adenine (HCA) solution on liver cold preservation, as well as to investigate the mechanisms underlying osmolarity-induced injury. Rat livers were cold-stored for 18 h at 4 °C using the different solutions and subsequently subjected to 2 h of normothermic machine perfusion (NMP) for functional assessment. The livers were categorized into four groups: HCA, UW, MS, and a control group. Liver function and histological changes were evaluated using biochemical markers such as lactate dehydrogenase (LDH), alongside histopathological analysis. Additionally, the expression of aquaporin 9 (AQP9) and hydrogen peroxide (H2O2) in hepatocytes was examined. Liver damage was significantly reduced in the UW and MS groups (p < 0.05). Histopathological analysis revealed a decrease in hepatic apoptosis and injury scores in the MS group compared to the HCA group (p < 0.05). No significant differences in liver function changes were observed between the MS and UW groups. Furthermore, examination of liver tissue showed increased H2O2 fluorescence intensity and decreased AQP9 protein levels in livers exhibiting vacuolar degeneration. In conclusion, the MS solution demonstrated superior effectiveness in preserving the liver during cold storage by inhibiting vacuolar degeneration caused by intracellular H2O2 accumulation.
{"title":"A betaine-contained solution reduced cold ischemia damage through inhibiting vacuolar degeneration in livers","authors":"Yu Wang , Tingting Lan , Shao-Hua Wu , Jiangong Ma , Xunfeng Zou","doi":"10.1016/j.trim.2024.102144","DOIUrl":"10.1016/j.trim.2024.102144","url":null,"abstract":"<div><div>A new osmoprotectant-containing multiple saccharide (MS) solution was formulated for this study. The primary objectives were to compare the effects of the MS solution with those of the University of Wisconsin (UW) solution and hypertonic citrate adenine (HCA) solution on liver cold preservation, as well as to investigate the mechanisms underlying osmolarity-induced injury. Rat livers were cold-stored for 18 h at 4 °C using the different solutions and subsequently subjected to 2 h of normothermic machine perfusion (NMP) for functional assessment. The livers were categorized into four groups: HCA, UW, MS, and a control group. Liver function and histological changes were evaluated using biochemical markers such as lactate dehydrogenase (LDH), alongside histopathological analysis. Additionally, the expression of aquaporin 9 (AQP9) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) in hepatocytes was examined. Liver damage was significantly reduced in the UW and MS groups (<em>p</em> < 0.05). Histopathological analysis revealed a decrease in hepatic apoptosis and injury scores in the MS group compared to the HCA group (p < 0.05). No significant differences in liver function changes were observed between the MS and UW groups. Furthermore, examination of liver tissue showed increased H<sub>2</sub>O<sub>2</sub> fluorescence intensity and decreased AQP9 protein levels in livers exhibiting vacuolar degeneration. In conclusion, the MS solution demonstrated superior effectiveness in preserving the liver during cold storage by inhibiting vacuolar degeneration caused by intracellular H<sub>2</sub>O<sub>2</sub> accumulation.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102144"},"PeriodicalIF":1.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569303","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}
Although some studies have reported kidney transplantation for end-stage kidney disease after hematopoietic stem cell transplantation, few have reported kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation. In this report, we describe a case of kidney transplantation after major ABO-incompatible HSCT and reviewed previous reports of kidney transplantation after hematopoietic stem cell transplantation. A 21-year-old male patient received major ABO-incompatible hematopoietic stem cell transplantation from an unrelated donor for B-lymphoblastic lymphoma. He developed chronic kidney disease requiring kidney replacement therapy because of drug toxicity and underwent ABO-compatible living donor kidney transplantation from his mother with standard immunosuppression. He had no anti-donor blood type antibody before kidney transplantation. Ten months after kidney transplantation, he is in good clinical condition with good renal function. Eighty-four cases of kidney transplantation after hematopoietic stem cell transplantation have been reported in literature. Among them, 25 recipients were from the same donor as hematopoietic stem cell transplantation. Out of these 25 recipients, 15 did not undergo maintenance immunosuppressive therapy. The low rejection incidence (14 %) and high rate of infection (32 %) and malignancy (10 %) suggest that kidney transplant recipients after hematopoietic stem cell transplantation are over-immunosuppressed. There were only three reports of kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation, including the present case. Kidney transplantation may be an effective renal replacement therapy for end-stage kidney disease after hematopoietic stem cell transplantation, even in ABO-incompatible hematopoietic stem cell transplantation cases.
{"title":"Kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation: A case report and literature review","authors":"Kazuro Kikkawa, Masahiro Tamaki, Kouhei Maruno, Tatsuya Hazama, Toshifumi Takahashi, Yuya Yamada, Masakazu Nakashima, Noriyuki Ito","doi":"10.1016/j.trim.2024.102143","DOIUrl":"10.1016/j.trim.2024.102143","url":null,"abstract":"<div><div>Although some studies have reported kidney transplantation for end-stage kidney disease after hematopoietic stem cell transplantation, few have reported kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation. In this report, we describe a case of kidney transplantation after major ABO-incompatible HSCT and reviewed previous reports of kidney transplantation after hematopoietic stem cell transplantation. A 21-year-old male patient received major ABO-incompatible hematopoietic stem cell transplantation from an unrelated donor for B-lymphoblastic lymphoma. He developed chronic kidney disease requiring kidney replacement therapy because of drug toxicity and underwent ABO-compatible living donor kidney transplantation from his mother with standard immunosuppression. He had no anti-donor blood type antibody before kidney transplantation. Ten months after kidney transplantation, he is in good clinical condition with good renal function. Eighty-four cases of kidney transplantation after hematopoietic stem cell transplantation have been reported in literature. Among them, 25 recipients were from the same donor as hematopoietic stem cell transplantation. Out of these 25 recipients, 15 did not undergo maintenance immunosuppressive therapy. The low rejection incidence (14 %) and high rate of infection (32 %) and malignancy (10 %) suggest that kidney transplant recipients after hematopoietic stem cell transplantation are over-immunosuppressed. There were only three reports of kidney transplantation after ABO-incompatible hematopoietic stem cell transplantation, including the present case. Kidney transplantation may be an effective renal replacement therapy for end-stage kidney disease after hematopoietic stem cell transplantation, even in ABO-incompatible hematopoietic stem cell transplantation cases.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102143"},"PeriodicalIF":1.6,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569306","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}
Pub Date : 2024-10-28DOI: 10.1016/j.trim.2024.102142
Tiago Xavier Silva , Evaldo Nascimento , Marcelo Gonçalves de Oliveira , Raquel A. Fabreti-Oliveira
Introduction
This study aimed to evaluate the reasons for kidney transplant dysfunction by analyzing allograft biopsy findings. We also compared clinical outcomes and graft survival rates in patients with and without de novo donor-specific antibodies (DSA).
Methods
This retrospective observational cohort study included 79 patients who underwent kidney allograft biopsy. The patients were divided into two groups based on the presence of anti-human leukocyte antigens (HLA) DSA antibodies. Laboratory evaluations included HLA-DSA and serum creatinine levels. The immunosuppressive therapy protocols were as follows: patients with single-antigen bead-measured sensitization (panel reactive antibody >50 %) received induction therapy, and all patients received triple therapy with tacrolimus or cyclosporine, prednisone, and mycophenolate sodium.
Results
Acute antibody-mediated rejection (AMR) occurred in 20.2 % of patients, whereas acute T-cell-mediated rejection (TCMR) was observed in 14 %. Interstitial fibrosis and tubular atrophy were observed in 53.8 % and 69.2 % of patients with de novo DSA, respectively, compared with 15.2 % and 87.9 % in the non-DSA group. Calcineurin inhibitors induced nephrotoxicity in 11.4 %, relapse of the underlying disease in 13.9 %, and infection in 7.6 % of biopsies. Differences in serum creatinine levels were observed between the de novo DSA and non-DSA groups from the third (p = 0.039), fifth (p = 0.028), and seventh years of follow-up (p = 0.012). The graft survival rate was lower in patients with de novo DSA than in those without (p = 0.036).
Conclusions
TCMR and AMR were the most common findings. The occurrence of AMR significantly impacted renal function and graft survival, and patients with de novo anti-HLA antibodies had poorer outcomes.
{"title":"Impact of renal allograft histopathological findings on transplant patient outcomes and graft survival: A retrospective single-center study","authors":"Tiago Xavier Silva , Evaldo Nascimento , Marcelo Gonçalves de Oliveira , Raquel A. Fabreti-Oliveira","doi":"10.1016/j.trim.2024.102142","DOIUrl":"10.1016/j.trim.2024.102142","url":null,"abstract":"<div><h3>Introduction</h3><div>This study aimed to evaluate the reasons for kidney transplant dysfunction by analyzing allograft biopsy findings. We also compared clinical outcomes and graft survival rates in patients with and without <em>de novo</em> donor-specific antibodies (DSA).</div></div><div><h3>Methods</h3><div>This retrospective observational cohort study included 79 patients who underwent kidney allograft biopsy. The patients were divided into two groups based on the presence of anti-human leukocyte antigens (HLA) DSA antibodies. Laboratory evaluations included HLA-DSA and serum creatinine levels. The immunosuppressive therapy protocols were as follows: patients with single-antigen bead-measured sensitization (panel reactive antibody >50 %) received induction therapy, and all patients received triple therapy with tacrolimus or cyclosporine, prednisone, and mycophenolate sodium.</div></div><div><h3>Results</h3><div>Acute antibody-mediated rejection (AMR) occurred in 20.2 % of patients, whereas acute T-cell-mediated rejection (TCMR) was observed in 14 %. Interstitial fibrosis and tubular atrophy were observed in 53.8 % and 69.2 % of patients with <em>de novo</em> DSA, respectively, compared with 15.2 % and 87.9 % in the non-DSA group. Calcineurin inhibitors induced nephrotoxicity in 11.4 %, relapse of the underlying disease in 13.9 %, and infection in 7.6 % of biopsies. Differences in serum creatinine levels were observed between the <em>de novo</em> DSA and non-DSA groups from the third (<em>p</em> = 0.039), fifth (<em>p</em> = 0.028), and seventh years of follow-up (<em>p</em> = 0.012). The graft survival rate was lower in patients with <em>de novo</em> DSA than in those without (<em>p</em> = 0.036).</div></div><div><h3>Conclusions</h3><div>TCMR and AMR were the most common findings. The occurrence of AMR significantly impacted renal function and graft survival, and patients with <em>de novo</em> anti-HLA antibodies had poorer outcomes.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102142"},"PeriodicalIF":1.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547669","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}
Pub Date : 2024-10-24DOI: 10.1016/j.trim.2024.102139
Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu
Background
To investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation.
Methods
We retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the “SNPassoc” package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery.
Results
NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, P < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (P = 0.0048).
Conclusion
Insertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis.
{"title":"Nuclear factor of activated T cell cytoplasmic 1 (NFATc1) insertion gene polymorphism as a possible trigger in acute T cell-mediated rejection (aTCMR) after kidney transplantation","authors":"Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu","doi":"10.1016/j.trim.2024.102139","DOIUrl":"10.1016/j.trim.2024.102139","url":null,"abstract":"<div><h3>Background</h3><div>To investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the “SNPassoc” package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery.</div></div><div><h3>Results</h3><div>NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, <em>P</em> < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (<em>P</em> = 0.0048).</div></div><div><h3>Conclusion</h3><div>Insertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102139"},"PeriodicalIF":1.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508759","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}
Pub Date : 2024-10-22DOI: 10.1016/j.trim.2024.102140
Mohamed I. Mohamed , Mattias Embretsen , Justin H. Nguyen
Background
Hepatic draining lymph nodes (HDLN) are implicated in allograft alloimmunity and tolerance. In contrast to experimental work, the role of HDLNs in human liver transplant (LT) is unknown due to lack of relevant clinical tissue.
Methods
During LT, the porta hepatis was dissected near the liver hilum during native hepatectomy. The HDLN in this region was taken prior to reperfusion (prereperfusion). Following complete reperfusion with recipient portal venous blood, hepatic arterial inflow into the allograft was established. As the recipient's common hepatic artery was fully mobilized, its HDLNs were removed and submitted to pathology (postreperfusion).
Results
Of 37 LTs performed between January 1, 2021, and July 9, 2022, 20 had both pre- and postreperfusion HDLNs archived (Group A); 11 had only postreperfusion HDLNs archived (Group B), and 6 had no archived HDLNs (Group C). Removing and archiving HDLNs did not increase operative times or transfusion requirements. For groups A, B, and C, mean (SD) warm ischemic times were 25.2 (2.0), 25.3 (3.2), and 28.3 (6.2) minutes, respectively (P > .05); operating times were 3.9 (0.7), 6.9 (7.8), and 7.9 (7.1) hours, respectively (A vs C, P = .017; C vs B, P > .05); and units of transfused packed red blood cells were 8.0 (3.8), 11.1 (10.3), and 12.2 (7.6), respectively (P > .05).
Conclusion
We describe an approach for clinical archiving of HDLNs obtained within the operative field during orthotopic LT in humans. Availability of relevant HDLNs is essential for investigations of primary immune responses potentially important in allograft alloimmunity and tolerance.
背景:肝引流淋巴结(HDLN)与同种异体免疫和耐受有关。与实验研究相反,由于缺乏相关的临床组织,HDLN 在人类肝移植(LT)中的作用尚不清楚:方法:在肝移植过程中,原发性肝切除术在肝门附近切除肝门。方法:肝移植过程中,在原肝切除术中解剖肝门附近,在再灌注(再灌注前)前提取该区域的高密度脂蛋白。用受体门静脉血液进行完全再灌注后,肝动脉血流入异体移植物。随着受体肝总动脉的完全活动,其高密度脂蛋白网被移除并提交病理检查(再灌注后):结果:在2021年1月1日至2022年7月9日期间进行的37例LT手术中,20例在再灌注前和再灌注后均有HDLN存档(A组);11例仅有再灌注后的HDLN存档(B组);6例无HDLN存档(C组)。移除和存档 HDLN 不会增加手术时间或输血需求。A 组、B 组和 C 组的平均(标清)温暖缺血时间分别为 25.2 (2.0)、25.3 (3.2) 和 28.3 (6.2) 分钟(P > .05);手术时间分别为 3.9 (0.7)、6.9 (7.8) 和 7.9 (7. 1) 小时(A 组 vs. B 组)。1)小时(A vs C,P = .017;C vs B,P > .05);输注包装红细胞的单位分别为 8.0 (3.8)、11.1 (10.3) 和 12.2 (7.6)(P > .05):我们描述了一种在人体正位LT过程中在手术区域内获得的HDLN的临床存档方法。获得相关的 HDLNs 对于研究可能对异体移植物同种免疫和耐受性很重要的原发性免疫反应至关重要。
{"title":"Hepatic draining lymph nodes in human liver transplant: Implications in alloimmunity and tolerance","authors":"Mohamed I. Mohamed , Mattias Embretsen , Justin H. Nguyen","doi":"10.1016/j.trim.2024.102140","DOIUrl":"10.1016/j.trim.2024.102140","url":null,"abstract":"<div><h3>Background</h3><div>Hepatic draining lymph nodes (HDLN) are implicated in allograft alloimmunity and tolerance. In contrast to experimental work, the role of HDLNs in human liver transplant (LT) is unknown due to lack of relevant clinical tissue.</div></div><div><h3>Methods</h3><div>During LT, the porta hepatis was dissected near the liver hilum during native hepatectomy. The HDLN in this region was taken prior to reperfusion (prereperfusion). Following complete reperfusion with recipient portal venous blood, hepatic arterial inflow into the allograft was established. As the recipient's common hepatic artery was fully mobilized, its HDLNs were removed and submitted to pathology (postreperfusion).</div></div><div><h3>Results</h3><div>Of 37 LTs performed between January 1, 2021, and July 9, 2022, 20 had both pre- and postreperfusion HDLNs archived (Group A); 11 had only postreperfusion HDLNs archived (Group B), and 6 had no archived HDLNs (Group C). Removing and archiving HDLNs did not increase operative times or transfusion requirements. For groups A, B, and C, mean (SD) warm ischemic times were 25.2 (2.0), 25.3 (3.2), and 28.3 (6.2) minutes, respectively (<em>P</em> > .05); operating times were 3.9 (0.7), 6.9 (7.8), and 7.9 (7.1) hours, respectively (A vs C, <em>P</em> = .017; C vs B, <em>P</em> > .05); and units of transfused packed red blood cells were 8.0 (3.8), 11.1 (10.3), and 12.2 (7.6), respectively (<em>P</em> > .05).</div></div><div><h3>Conclusion</h3><div>We describe an approach for clinical archiving of HDLNs obtained within the operative field during orthotopic LT in humans. Availability of relevant HDLNs is essential for investigations of primary immune responses potentially important in allograft alloimmunity and tolerance.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102140"},"PeriodicalIF":1.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508746","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}
Pub Date : 2024-10-21DOI: 10.1016/j.trim.2024.102137
Fizza Zulfiqar , Moazzam Shahzad , Muhammad Kashif Amin , Abhinav Vyas , Zouina Sarfraz , Anika Zainab , Hana Qasim , Dania Kaur , Naghmeh Khavandgar , Forat Lutfi , Peiman Hematti , Joseph P. McGuirk , Muhammad Umair Mushtaq
Background
Chimeric antigen receptor T cell (CAR-T) therapy is an emerging form of immunotherapy that has recently gained recognition for treating hematological malignancies. This successful utilization of CAR-T therapy has attracted interest in its application in refractory rheumatological diseases. Here, we will review the use of CAR-T therapy in rheumatological diseases.
Methods
Per PRISMA guidelines, a comprehensive literature search was performed on PubMed, Cochrane, and ClinicalTrials.gov using keywords for ‘CAR-T cell therapy’ and ‘Rheumatological diseases’ from inception to December 9, 2023. After screening 2977 articles, six studies reporting outcomes of CAR-T cell therapies in patients with underlying autoimmune /rheumatological diseases. Descriptive analysis was performed to represent demographics and clinical outcomes.
Results
A total of 101 adult patients from six studies were included in this systematic review. The median age of the participants was 50.8 years (IQR: 14.875), with ages ranging from 18 to 83 years. The included studies comprised 2 case reports, 1 case series, one observational study, and two clinical trials. The studies were conducted globally, including USA, Germany, and China. The underlying rheumatologic conditions were systemic lupus erythematosus (17.8 %), rheumatoid arthritis (23.8 %), myasthenia gravis (13.8 %), neuromyelitis optica (11.9 %), and others (32.7 %). The target of CAR-T therapy included CD-19 in four studies and B cell maturation antigen (BCMA) in two studies. All the patients were on prior therapy, including glucocorticoids and disease-modifying antirheumatic drugs. Follow-up ranged from a month to 1.5 years. Most of the studies reported improvement in the symptoms and decline in serological biomarkers of the underlying disease. The notable outcomes in the included studies were a 100 % response rate in five out of six studies. Grade 1 and 2 cytokine release syndrome (CRS) was observed in five studies. Only one study reported Grade 3 or higher CRS. 2 patients (1.98 %) developed neurotoxicity among the adverse effects.
Conclusion
CAR-T cell therapy is a paradigm shift in managing rheumatologic diseases, with symptomatic improvement and biochemical control of these diseases. Although preliminary evidence indicates promising results, long-term follow-up and prospective clinical trials are needed to establish optimal timing and assess the safety and efficacy of CAR-T immunotherapy.
{"title":"Outcomes with chimeric antigen receptor T-cell therapy in Rheumatological disorders: A systematic review","authors":"Fizza Zulfiqar , Moazzam Shahzad , Muhammad Kashif Amin , Abhinav Vyas , Zouina Sarfraz , Anika Zainab , Hana Qasim , Dania Kaur , Naghmeh Khavandgar , Forat Lutfi , Peiman Hematti , Joseph P. McGuirk , Muhammad Umair Mushtaq","doi":"10.1016/j.trim.2024.102137","DOIUrl":"10.1016/j.trim.2024.102137","url":null,"abstract":"<div><h3>Background</h3><div>Chimeric antigen receptor T cell (CAR-T) therapy is an emerging form of immunotherapy that has recently gained recognition for treating hematological malignancies. This successful utilization of CAR-T therapy has attracted interest in its application in refractory rheumatological diseases. Here, we will review the use of CAR-T therapy in rheumatological diseases.</div></div><div><h3>Methods</h3><div>Per PRISMA guidelines, a comprehensive literature search was performed on PubMed, Cochrane, and <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> using keywords for ‘CAR-T cell therapy’ and ‘Rheumatological diseases’ from inception to December 9, 2023. After screening 2977 articles, six studies reporting outcomes of CAR-T cell therapies in patients with underlying autoimmune /rheumatological diseases. Descriptive analysis was performed to represent demographics and clinical outcomes.</div></div><div><h3>Results</h3><div>A total of 101 adult patients from six studies were included in this systematic review. The median age of the participants was 50.8 years (IQR: 14.875), with ages ranging from 18 to 83 years. The included studies comprised 2 case reports, 1 case series, one observational study, and two clinical trials. The studies were conducted globally, including USA, Germany, and China. The underlying rheumatologic conditions were systemic lupus erythematosus (17.8 %), rheumatoid arthritis (23.8 %), myasthenia gravis (13.8 %), neuromyelitis optica (11.9 %), and others (32.7 %). The target of CAR-T therapy included CD-19 in four studies and B cell maturation antigen (BCMA) in two studies. All the patients were on prior therapy, including glucocorticoids and disease-modifying antirheumatic drugs. Follow-up ranged from a month to 1.5 years. Most of the studies reported improvement in the symptoms and decline in serological biomarkers of the underlying disease. The notable outcomes in the included studies were a 100 % response rate in five out of six studies. Grade 1 and 2 cytokine release syndrome (CRS) was observed in five studies. Only one study reported Grade 3 or higher CRS. 2 patients (1.98 %) developed neurotoxicity among the adverse effects.</div></div><div><h3>Conclusion</h3><div>CAR-T cell therapy is a paradigm shift in managing rheumatologic diseases, with symptomatic improvement and biochemical control of these diseases. Although preliminary evidence indicates promising results, long-term follow-up and prospective clinical trials are needed to establish optimal timing and assess the safety and efficacy of CAR-T immunotherapy.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102137"},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508761","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}
Pub Date : 2024-10-21DOI: 10.1016/j.trim.2024.102141
Júlia Plentz Portich , Aline Sinhorelo Ribeiro , Lisandra Della Costa Rigoni , Lúcia Mariano da Rocha Silla , Claudia Caceres Astigarraga , Liane Esteves Daudt , Alessandra Aparecida Paz
Background
Engraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD).
Objective
To investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution.
Study design
This retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria.
Results
Of the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (P < 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (P = 0.01; Student's t-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (P < 0.05, Pearson's chi-squared test).
Conclusions
The general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES.
背景:移植综合征(ES)是造血干细胞移植(HSCT)后中性粒细胞恢复期间可能出现的一种临床症状。由于诊断标准不一,且ES与移植物抗宿主疾病(GVHD)之间的关系存在争议,因此诊断具有挑战性:研究设计:这项回顾性队列研究纳入了2015年1月至2016年12月期间在巴西一家三级医院接受异基因造血干细胞移植(alloHSCT)的患者。ES根据Spitzer或Maiolino标准进行诊断:在接受同种异体造血干细胞移植的79名患者中,有3人出现移植失败,被排除在分析之外。根据Spitzer和Maiolino的标准,14岁以上患者的ES发生率分别为16.5%和9.8%,儿童患者的ES发生率为28.6%,两者之间存在显著相关性(P 结论:ES的发生率与移植失败率之间存在显著相关性:本组人群中 ES 的总体发病率与文献报道一致。值得注意的是,ES 与住院时间延长有关(比没有 ES 的患者多住院 14 天)。此外,使用抗生素治疗耐多药细菌的患者 ES 发生率更高。
{"title":"Institutional insights into engraftment syndrome: A cohort study on allogeneic transplantation outcomes","authors":"Júlia Plentz Portich , Aline Sinhorelo Ribeiro , Lisandra Della Costa Rigoni , Lúcia Mariano da Rocha Silla , Claudia Caceres Astigarraga , Liane Esteves Daudt , Alessandra Aparecida Paz","doi":"10.1016/j.trim.2024.102141","DOIUrl":"10.1016/j.trim.2024.102141","url":null,"abstract":"<div><h3>Background</h3><div>Engraftment syndrome (ES) is a clinical condition that may occur during neutrophil recovery after hematopoietic stem cell transplantation (HSCT). Diagnosis is challenging because of the varying diagnostic criteria and the controversial relationship between ES and graft-versus-host disease (GVHD).</div></div><div><h3>Objective</h3><div>To investigate the incidence of ES and its relationship with GVHD in patients undergoing allogeneic HSCT at our institution.</div></div><div><h3>Study design</h3><div>This retrospective cohort study included patients who underwent allogeneic HSCT (alloHSCT) at a Brazilian tertiary hospital between January 2015 and December 2016. ES was diagnosed based on the Spitzer or Maiolino criteria.</div></div><div><h3>Results</h3><div>Of the 79 patients who underwent alloHSCT, three presented with graft failure and were excluded from the analysis. The incidence of ES, according to both Spitzer's and Maiolino's criteria, was 16.5 % and 9.8 % in patients older than 14 years and 28.6 % in children, respectively, with a significant correlation (<em>P</em> < 0.05, Pearson's chi-squared test). ES was associated with prolonged hospitalization (<em>P</em> = 0.01; Student's <em>t</em>-test). No correlation was observed between acute GVHD and ES. There was a positive correlation between the use of broad-spectrum antibiotics against multidrug-resistant bacteria and ES development (<em>P</em> < 0.05, Pearson's chi-squared test).</div></div><div><h3>Conclusions</h3><div>The general incidence of ES in this cohort was consistent with that reported in the literature. Remarkably, ES was associated with prolonged hospitalization (14 days longer than in patients without ES). Moreover, patients who used antibiotics against multidrug-resistant bacteria had a higher incidence of ES.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102141"},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508758","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}
Pub Date : 2024-10-21DOI: 10.1016/j.trim.2024.102138
Nele Van De Winkel , Marina Gabriela M.C. Mori da Cunha , Antoine Dubois , Ewout Muylle , Lisanne Terrie , Ina Hennion , Gert De Hertogh , Heleen Fehervary , Lieven Thorrez , Marc Miserez , Jacques Pirenne , André D’Hoore , Laurens J. Ceulemans
Complex abdominal wall repair remains a major surgical challenge. In transplant patients, non-vascularized rectus fascia (NVRF) is successfully used to bridge the defect. To extrapolate this to non-transplant patients, we developed a rabbit model of NVRF-transplantation without immunosuppression comparing syngeneic versus allogeneic transplants. Short-term outcome (4 weeks) was evaluated macroscopically (ingrowth, seroma/hematoma, herniation, and infection), histologically at the graft interface and center (inflammation, neovascularization, and collagen deposition) and by mechanical testing. In both groups a similar macroscopic ingrowth of the NVRF was observed. In the syn-group, one seroma and one hematoma was seen. Two small herniations were detected at the suture line in the allo-group. No surgical site infections were observed. Histologically, graft neovascularization was observed in all animals. Infiltration of T-lymphocytes was seen at the graft interface in both groups, but more in the allo-group (p < 0.0001). Deposition of collagen was not different between groups. Macrophages were present in both groups around sutures and in the center more abundantly in the allo-group (p = 0.0001). Graft stiffness and strength were similar for both groups. With this model, we showed that allogeneic transplantation without immunosuppression results in favorable short-term inflammatory and mechanical outcomes. Long-term experiments are needed to further evaluate the effect on graft integration and hernia development.
复杂的腹壁修复仍然是一项重大的手术挑战。在移植患者中,无血管直肌筋膜(NVRF)被成功用于弥补缺损。为了将这一方法推广到非移植患者中,我们建立了一个无免疫抑制的无血管直肌筋膜移植兔模型,对同种异体移植进行了比较。对短期结果(4 周)进行了宏观评估(生长、血清肿/血肿、疝和感染)、移植物界面和中心的组织学评估(炎症、新生血管和胶原沉积)以及机械测试。在两组患者中,都观察到了类似的新生血管再造阵列的宏观生长情况。在同步组中,发现了一个血清肿和一个血肿。异体组在缝合线处发现两个小的疝气。未观察到手术部位感染。从组织学角度看,所有动物均观察到移植物新生血管。两组动物的移植物界面都出现了 T 淋巴细胞浸润,但异体组的 T 淋巴细胞浸润更多(p<0.05)。
{"title":"Allogeneic abdominal non-vascularized rectus fascia transplantation without immunosuppression equals syngeneic transplantation in a rabbit model at short-term follow-up","authors":"Nele Van De Winkel , Marina Gabriela M.C. Mori da Cunha , Antoine Dubois , Ewout Muylle , Lisanne Terrie , Ina Hennion , Gert De Hertogh , Heleen Fehervary , Lieven Thorrez , Marc Miserez , Jacques Pirenne , André D’Hoore , Laurens J. Ceulemans","doi":"10.1016/j.trim.2024.102138","DOIUrl":"10.1016/j.trim.2024.102138","url":null,"abstract":"<div><div>Complex abdominal wall repair remains a major surgical challenge. In transplant patients, non-vascularized rectus fascia (NVRF) is successfully used to bridge the defect. To extrapolate this to non-transplant patients, we developed a rabbit model of NVRF-transplantation without immunosuppression comparing syngeneic versus allogeneic transplants. Short-term outcome (4 weeks) was evaluated macroscopically (ingrowth, seroma/hematoma, herniation, and infection), histologically at the graft interface and center (inflammation, neovascularization, and collagen deposition) and by mechanical testing. In both groups a similar macroscopic ingrowth of the NVRF was observed. In the <em>syn</em>-group, one seroma and one hematoma was seen. Two small herniations were detected at the suture line in the allo-group. No surgical site infections were observed. Histologically, graft neovascularization was observed in all animals. Infiltration of T-lymphocytes was seen at the graft interface in both groups, but more in the allo-group (<em>p</em> < 0.0001). Deposition of collagen was not different between groups. Macrophages were present in both groups around sutures and in the center more abundantly in the allo-group (<em>p</em> = 0.0001). Graft stiffness and strength were similar for both groups. With this model, we showed that allogeneic transplantation without immunosuppression results in favorable short-term inflammatory and mechanical outcomes. Long-term experiments are needed to further evaluate the effect on graft integration and hernia development.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102138"},"PeriodicalIF":1.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508760","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}
Pub Date : 2024-10-04DOI: 10.1016/j.trim.2024.102136
Raza Ullah Asif, Eijaz Ghani, Muhammad Ali Rathore, Saadiya Mushtaq, Faraz Ahmed, Hammad Hussain
Background
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.
Methods
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.
Results
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).
Conclusion
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.
背景:由于免疫抑制,BK 多瘤病毒感染给器官移植受者带来了巨大挑战,导致 BK 病毒相关性肾病(BKVAN)和相当大的移植物丢失风险。筛查和及时减少免疫抑制对避免这些后果至关重要。我们研究了肾移植术后受者出现 BK 病毒尿(尿液中病毒载量)的频率及其与年龄、病毒载量和病毒再激活时间的关系:这项前瞻性队列研究于 2023 年 1 月 1 日至 12 月 31 日在拉瓦尔品第三级医院进行,为期 12 个月。在随访评估期间,每三个月收集 108 名肾移植受者的尿液标本并分析 BK 病毒。使用 TANbead 提取器提取 DNA,并使用 Bio-Rad CFX-96 热循环仪和 Sacace TM 扩增试剂盒进行扩增。数据使用 SPSS 27 版进行分析:结果:在 108 例肾移植受者中,16.7% 的病例检测出 BK 病毒。女性 BK 病毒感染率(20%)高于男性(16%)。大多数阳性病例年龄在 41-60 岁之间(61.1%)。大多数患者(66.6%)的病毒载量低于 100 万拷贝/毫升。BK 病毒主要在移植后第三季度(7 至 9 个月)检测到。年龄与病毒载量之间进行了卡方检验,结果显示两者之间存在显著关联(p = 0.01)。同样,性别与病毒载量也有显著关系(P = 0.019):研究表明,在我们的小规模队列中,肾移植后最初 12 个月内 BK 病毒感染率为 16.7%。受者年龄与病毒载量和病毒再激活时间相关:中年受者的病毒载量较高。在最初的九个月中,BK 病毒感染率逐渐增加,在移植后的第三季度达到高峰。
{"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":"10.1016/j.trim.2024.102136","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 (<em>p</em> = 0.01). Similarly, gender and viral load also showed a significant relationship (<em>p</em> = 0.019).</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23304,"journal":{"name":"Transplant immunology","volume":"87 ","pages":"Article 102136"},"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}