Acute Cellular Rejection Episodes Research Articles

Induction Versus Maintenance Immunosuppression After Intestinal Transplant: Determining Which Treatment Most Impacts Long-Term Patient And Graft Survival.

Immunosuppressive strategies for intestinal transplant have changed over time. However, specific intestinal transplant-oriented protocols and reports on long-term maintenance regimens are scarce. Our objective was to evaluate the impact of 2 different initial immunosuppressive protocols based on thymoglobulin (group A) and basiliximab (anti-interleukin 2 antibody) (group B) and of changes to maintenance immunosuppression over long-term follow-up in intestinal transplant recipients. We performed a retrospective analysis of a prospectively established protocol for intestinal transplant immunosuppression, conducted between May 2006 and December 2020. We analyzed 51 intestinal transplant recipients, with 6 patients excluded because of early death or graft loss. Acute cellular rejection frequency and grade, number of acute cellular rejection episodes, time to the first acute cellular rejection episode, response to treatment, number of patients who progressed to chronic allograft rejection, kidney function, infections, incidence of posttransplant lymphoproliferative disorder and graft-versus-host disease, and patient and graft survival were analyzed. In the study groups, there were 87 acute cellular rejection episodes in 45 patients (33 in group A and 54 in group B). We found degree of acute cellular rejection to be mild in 45 patients, moderate in 18, and severe in 24 (not significant between groups). Our comparison of induction therapy (thymoglobulin [group A] vs interleukin 2 antibody [group B]) did not show any statistical difference during clinical followup. Long-term review showed that all patients were on tacrolimus. Five-year patient and graft survival rates were 62% and 45% for group A and 54% and 46% for group B, respectively (not significant). Long-term patient and graft outcomes reflected the use of an individualized follow-up with adjustments and changes in immunosuppressive medications according to the patient's clinical course and complications rather than based on the induction immunosuppressive protocol used.

420.6: Transplantation of Organs From SARS-CoV-2-Positive Donors To Uninfected (Non-lung) Solid Organ Transplant Recipients Has Not Resulted in Significant SARS-CoV-2 Related Morbidity Or Mortality

Introduction: The SARS-CoV-2 pandemic has conferred significant morbidity and mortality across the globe, especially for solid organ transplant (SOT) recipients. This has led to reluctance of using organs from SARS-CoV-2 infected donors due to concerns of disease transmission. However, this must be offset with an increase in wait list mortality. We sought to evaluate the use of organs from SARS-CoV-2 donors into (non-Lung) Solid Organ Transplant Recipients in a prospective fashion. Methods: We evaluated the use of organs from SARS-CoV-2 donors between 6/17/2021 to 2/24/2022. 18 patients were transplanted with SARS-CoV-2-positive donor (COVID+) organs: 3 heart, 4 liver, and 11 kidney recipients. SOT recipients were tested for presence of SARS-CoV-2 by RT-PCR prior to and after their operations. Induction immunosuppression was standard and not altered from protocol. Postoperatively, recipients were kept in modified droplet precautions and received post-exposure treatment recommended by Transplant Infectious Disease. Treatment regimens included remdesivir and monoclonal antibodies directed against SARS-CoV-2 (Figure 1). Perioperative and post discharge care was administered by a multidisciplinary care team with no significant alterations in care protocols. Results: SOT recipients of COVID+ organs at our institution have not experienced any significant morbidity or mortality from SARS-CoV-2. All patients are alive at current follow up with excellent allograft function with a median follow up for heart, liver, and kidney recipients of 235, 67, and 86 days respectively. All patients were vaccinated except for one liver patient who was status 1A due to fulminant acute liver failure. 13/18 patients had post-operative nasopharyngeal swabbing for RT-PCR based viral testing and two tested positive for SARS-CoV-2 at POD #8. Neither patient experience clinical symptoms of disease. Use of of SARS-CoV-2 did not appear to increase inpatient hospital stay. Median LOS for heart, liver, and kidney recipients was 40, 12.3, and 7.4 days respectively. Neither pre-transplant vaccination, use of COVID+ organs, nor post exposure prophylaxis resulted in increased risk of immunologic complications as only one recipient (heart) has experienced an acute cellular rejection episode to date Conclusion: Our experience indicates that COVID+ organs can be utilized successfully. The decision to use these organs was based on organ quality, individual patient need at the time the organ offer was made and whether a potential similar quality, COVID negative organ would be available to the patient in the near future. As evidenced by our data, successful use of COVID+ organs is dependent on multidisciplinary wait list and perioperative management to ensure appropriate donor:recipient selection and mitigation of transmission risk with use of post-exposure prophylaxis.

The Role of Left Atrial Longitudinal Strain in the Diagnosis of Acute Cellular Rejection in Heart Transplant Recipients.

Our aim was to investigate the role of left atrial longitudinal strain (LALS) in the non-invasive diagnosis of acute cellular rejection (ACR) episodes in heart transplant (HTx) recipients. Methods: We performed successive echocardiographic exams in 18 consecutive adult HTx recipients in their first year after HTx within 3 h of the routine surveillance endomyocardial biopsies (EMB) in a single center. LALS parameters were analyzed with two different software. We investigated LALS association with ACR presence, as well as inter-vendor variability in comparable LALS values. Results: A total of 147 pairs of EMB and echo exams were carried out. Lower values of LALS were significantly associated with any grade of ACR presence. Peak atrial longitudinal strain (PALS) offered the best diagnostic value for any grade of ACR, with a C statistic of 0.77 using one software (95% CI 0.68–0.84, p < 0.0005) and 0.64 with the other (95% CI 0.54–0.73, p = 0.013) (p = 0.02 for comparison between both curves). Reproducibility between comparable LALS parameters was poor (intraclass correlation coefficients were 0.60 for PALS, 95% CI 0.42–0.73, p < 0.0005; and 0.42 for PALS rate, 95% CI −0.13–0.68, p < 0.0005). Conclusions: LALS variables might be a sensitive marker of ACR in HTx recipients, principally discriminating between those studies without rejection and those with any grade of ACR. Inter-vendor variability was significant.

Risk factors and outcomes of sudden cardiac arrest in pediatric heart transplant recipients

Sudden cardiac arrest (SCA) is a prevailing cause of mortality after pediatric heart transplant (HT) but remains understudied. We analyzed the incidence, outcomes, and risk factors for SCA at our center. Retrospective review of all pediatric HT patients at our center from January 1, 2009 to January 1, 2021. SCA was defined as an abrupt loss of cardiac function requiring cardiopulmonary resuscitation and/or mechanical circulatory support (MCS). Events that occurred in the setting of limited resuscitative wishes, or while on MCS were excluded. Patient characteristics and risk factors were analyzed. Fourteen of 254 (6%) experienced SCA at a median of 3 (1, 4) years post-HT. Seven (50%) events occurred out-of-hospital. Eleven (79%) died from their initial event, 2 (18%) after failure to separate from extracorporeal membrane (ECMO). In univariate analysis, black race, younger donor age, prior acute cellular rejection (ACR) episode, pacemaker and/or ICD in place, and pre-mortem diagnosis of allograft vasculopathy were associated with SCA (P=.003-0.02). In multivariable analysis, history of ACR, younger donor age, and black race retained significance. [OR=6.3, 95% CI: 1.6-25.4, P=.01], [OR=0.9, 95% CI: 0.8-1, P=.04], and [OR=7.3, 95% CI: 1.1-49.9, P=.04], respectively. SCA occurred in 3 patients with a functioning ICD or pacemaker, which failed to restore a perfusing rhythm. SCA occurs relatively early after pediatric HT and is usually fatal. Half of events happen at home. Those who received younger donors, have a history of ACR, or are of black race are at increased risk. ICDs/pacemakers may offer limited protection.

Induction Strategies in Lung Transplantation: Alemtuzumab vs. Basiliximab a Single-Center Experience.

BackgroundInduction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction therapy. At our institution, we have two induction strategies, basiliximab, and alemtuzumab. The goal of this manuscript is to share our experience and practice since this is an area of controversy.MethodsWe retrospectively reviewed 807 lung transplants performed at our institution between 2011 and 2020. Indications for the use of the basiliximab protocol were as follows: patients over the age of 70 years, history of cancer, hepatitis C virus or human immunodeficiency virus infection history, and cytomegalovirus or Epstein-Barr virus (donor positive/ recipient negative). In the absence of these clinical factors, the alemtuzumab protocol was used.Results453 patients underwent alemtuzumab induction and 354 patients underwent basiliximab. There were significant differences in delayed chest closure (24.7% alemtuzumab vs 31.4% basiliximab, p = 0.037), grade 3 primary graft dysfunction observed within 72 hours (19.9% alemtuzumab vs 29.9% basiliximab, p = 0.002), postoperative hepatic dysfunction (8.8% alemtuzumab vs 14.7% basiliximab, p = 0.009), acute cellular rejection in first year (39.1% alemtuzumab vs 53.4% basiliximab, p < 0.001). The overall survival rate of the patients with alemtuzumab induction was significantly higher than those of the patients with basiliximab induction (5 years survival rate: 64.1% alemtuzumab vs 52.3%, basiliximab, p < 0.001). Multivariate Cox regression analysis confirmed lower 5-year survival for basiliximab induction (HR = 1.41, p = 0.02), recipient cytomegalovirus positive (HR = 1.49, p = 0.01), postoperative hepatic dysfunction (HR = 2.20, p < 0.001), and acute kidney injury requiring renal replacement therapy (HR = 2.27, p < 0.001).ConclusionsIn this single center retrospective review, there was a significant difference in survival rates between induction strategies. This outcome may be attributable to differences in recipient characteristics between the groups. However, the Alemtuzumab group experienced less episodes of acute cellular rejection within the first year.

Investigating Defects of Esophageal Motility in Lung Transplant Recipients.

BackgroundLung transplant patients are at risk of developing chronic lung allograft dysfunction (CLAD) of which bronchitis obliterans syndrome (BOS) is the most common. These patients also are noted to develop gastrointestinal (GI) disease. Gastroesophageal reflux disease (GERD) is implicated in BOS, and diagnosis and treatment of GERD may help to decrease incidence of BOS.MethodsA total of 131 lung transplant recipients with post-transplant evaluation between 2012 and 2019 were studied. Of 60 post-transplant evaluations with at least 6 months of post-transplant follow-up that included impedance testing, high-resolution manometry (HRM), and pH testing, procedures were performed according to recognized standards.ResultsOf 60 patients, 56 (93%) were alive at 1-year post-transplant. The patients were found to have high rates of GI motility diseases: 37 patients (62%) had abnormal impedance testing, 50 patients (83%) had abnormal HRM results, 22 patients (37%) had abnormal pH test results. There was associated high rejection rates in patients with abnormal esophageal motility. There were 37 patients that had abnormal impedance test results and of those 25 patients (67%) developed rejection. Fifty patients had abnormal post-transplant HRM studies, 33 (66%) had an acute cellular rejection episode. Twenty-two patients had abnormal pH results, with 14 (63%) having an acute cellular rejection.ConclusionsPatients undergoing lung transplantation were found to have increased incidence of abnormal GI motility studies of the esophagus. These patients were further found to have increased rejection rates and BOS which has been associated with worsened mortality. Developing a formalized pre- and post-transplant motility study process, using evolving technologies for these patients, may provide guidance of at-risk patients for CLAD and early treatment to prevent CLAD.

Progressive Multifocal Leukoencephalopathy Presenting as Expressive Aphasia in a Lung Transplant Recipient

IntroductionProgressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR).Case ReportA 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits.SummaryPML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management. Progressive multifocal leukoencephalopathy (PML) is a demyelinating brain disease caused by reactivation of JC virus in immunocompromised patients. PML typically manifests with subacute neurologic deficits including altered mental status, motor deficits, limb ataxia, gait ataxia, and visual symptoms. We report an atypical presentation of PML in a lung transplant recipient (LTR). A 71-year-old LTR received rituximab induction followed by a combination of mycophenolate mofetil, tacrolimus, and prednisone. He had a single episode of minimal acute cellular rejection early after LT, but never required significantly augmented immunosuppression. Notably, he had mild leukopenia throughout his post-LT course (WBC count 3-4 thousand/µL), and he had no response to 4 doses of the Pfizer SARS-CoV-2 vaccine, suggesting advanced immunosuppression. At 14 months after LT, the patient reported progressive anomia and aphasia, but no other neurologic deficits. MRI showed an abnormal increased T2/FLAIR signal in the left posterior parieto-occipital subcortical white matter, involving subcortical U fibers, characteristic of PML (Figure A, C). Serum JC virus PCR showed low-level viremia, but CSF from 2 lumbar punctures was PCR negative. Thus, he was diagnosed with possible PML, and immunosuppression was narrowed to a combination of tacrolimus (goal trough 4-6) and prednisone, 5 mg daily. Despite reduced immunosuppression, a repeat MRI 2 months after the initial diagnosis showed worsening PML (Figure B, D) and his symptoms progressed to severe anomia, aphasia, and cortical blindness, but still no motor deficits. PML is a rare, albeit well described, complication of LT, but presentation with only anomia and aphasia is unusual. Without CSF viral isolation, a definitive diagnosis requires brain tissue; however, MRI changes involving subcortical U fibers in the parieto-occipital area are highly characteristic. Early recognition allows for expeditious management.

Development of De Novo Donor Specific Antibodies Following COVID-19 Vaccination in Cardiac Transplant

PurposeSome transplant patients mount an insufficient response to standard COVID-19 vaccine (COVAX) dosing and a booster dose has now been approved. Vaccination carries the theoretical risk of stimulating antibody production to the donor. There are no prior studies surveying de novo donor specific HLA antibodies (dnDSA) after COVAX. HLA-DQ is the most common dnDSA post cardiac transplant and is associated with worse outcomes. We reviewed the development of dnDSA to HLA-DQ in cardiac transplant patients after COVAX.MethodsDSA testing (luminex single antigen bead) was performed routinely at the time of surveillance endomyocardial biopsy. We retrospectively recorded any dnDSA to HLA-DQ with MFI >1000 after COVAX. We further identified a historical cohort (pre vaccination) of 32 patients who had DSA testing a minimum of 5 months after transplant.Results32 adult patients completed COVAX (16 Pfizer-BioNTech, 8 Moderna, 8 Johnson and Johnson) 3-79 mths after transplantation. 16 patients had DSA testing 1-5 mths post COVAX (4-84 mths post transplant) (Table 1). Three patients (18.8 %) demonstrated dnDSA to HLA-DQ (MFI 6360-25,824) 10-20 weeks post COVAX and all had episodes of high grade acute cellular rejection. One additional patient had rejection post COVAX without dnDSA. All 3 patients with dnDSA had robust response to the vaccine with antibodies to spike protein RBD of > 200 U/ml (Elecsys®). Eight vaccinated patients without dnDSA had anti-RBD testing, half had titres > 200 U/ml. In the historical pre COVAX cohort, 3 patients (9 %) demonstrated dnDSA (2022-25480 MFI), one of these had cellular rejection and one developed antibody mediated rejection.ConclusionOne fifth of cardiac transplant recipients developed dnDSA in the weeks following COVAX, all associated with rejection. While no definitive conclusions may be drawn, we believe these data suggest the need for immunological surveillance after COVAX. This may be even more important after a booster dose.

Amyloid-Targeted Immunosuppression After Orthotopic Heart Transplantation

<h3>Purpose</h3> The optimal immunosuppressive therapy (IST) for patients with AL amyloid undergoing orthotopic heart transplantation (OHT) is not well defined. Our study aims to present the IST and outcomes after OHT in patients with cardiac amyloidosis at a large quaternary university hospital. <h3>Methods</h3> In a retrospective chart review, we performed a case series of all patients with AL amyloid who underwent OHT from Jan 2017 to Oct 2020. We assessed their IST and outcomes of survival, infection and rejection. <h3>Results</h3> We identified 7 patients with AL amyloidosis who underwent OHT. Three patients (43%) had Mayo Stage 3, and 4 (57%) patients had stage 4. Autologous stem cell transplant (ASCT) was performed in 4 patients with a median time from OHT to ASCT of 429 days. In patients who had bone marrow biopsy, amyloid was present in 21% and the mean plasma cells visualized by immunohistochemistry was 4.41%. IST after OHT consisted of a calcineurin inhibitor, antimetabolite and steroids initially. Some required treatment with bortezomib/daratumumab for sub-optimal duration or hematologic response to AL amyloid therapies prior to OHT at which time antimetabolite was stopped. Median time to antimetabolite withdrawal was 317 days. Median times to introduction of daratumumab and bortezomib after OHT were 283 and 388 days, respectively. Figure 1 displays the time series of IST. Renal involvement was the more prevalent extracardiac organ (57%), followed by gastrointestinal (43%), carpal tunnel (29%), and peripheral neuropathy (29%). We did not observe any mortality, graft failure, episodes of acute cellular or antibody-mediated rejection. One patient had clostridium difficile infection who was admitted for monitoring. <h3>Conclusion</h3> In those that require ongoing AL amyloid therapies following OHT, it may be safe to discontinue antimetabolite in efforts to minimize complications from over-immunosupression without compromising risk of rejection. Personalized IST in this traditionally high-risk population should be considered.

Pancreatitis as a Potential Trigger for Early, Severe Accelerated Cardiac Allograft Vasculopathy: A Case Report

<h3>Introduction</h3> Accelerated cardiac allograft vasculopathy (CAV) is an uncommon ominous finding after heart transplantation (HTx), with unclear pathophysiology and poor prognosis. We present a case of accelerated CAV in a heart recipient with recurrent acute pancreatitis. <h3>Case Report</h3> A 38 year-old male with non-ischemic dilated cardiomyopathy, on INTERMACS 3 profile, was transplanted with a 23 year-old donor heart. Post-operatively, acute ischemic pancreatitis ensued with recurrent relapses requiring readmissions. Maintenance immunosuppression was suboptimal due to concerns regarding pancreatic toxicity, and 4 episodes of high-grade acute cellular rejection occurred in the 1st year. By 9 months post-transplant, coronary angiography showed severe multivessel CAV (Figure 1A and 1B). In order to delay its progression, bortezomib was initiated due to presumed humoral response triggers. Staged PCI was planned; however, the patient died suddenly before the procedure was attempted. <h3>Summary</h3> Aggressive accelerated CAV developing early post HTx is rare and almost invariably associated with dismal prognosis. Inflammatory and/or humoral responses may play an important role in such forms of very fast-developing disease, which may course with an acute, predominant component of vasculitis. Herein, pro-inflammatory state set up by recurrent pancreatitis may have contributed to the clinical picture (Figure 1C).Increased biomarkers, as pro-inflammatory cytokines and fibroblast growth factors, have been linked to advanced CAV. Likewise, pancreatitis pathogenesis is related to cytokine activation with remarkable systemic inflammatory response. A high-grade inflammatory state secondary to recurrent acute pancreatitis may have been a major trigger for early, severe CAV development in this case. Understanding predictors of increased risk for severe accelerated CAV may facilitate the institution of close surveillance and targeted therapies for this challenging scenario.

Analysis of T Cell Populations in Clinically Stable ISHLT Grade A1 Lesions

<h3>Purpose</h3> CD4+FOXP3+ Regulatory T cells (Tregs) may modulate acute cellular rejection (ACR)-associated immune responses and the progression of ACR to Chronic Lung Allograft Dysfunction (CLAD) following lung transplantation (LTx). Treg stability is enhanced by demethylation of the Treg-specific demethylated region (TSDR) in the Foxp3 locus. Grade A1 ACR is not treated in clinically stable patients at our centre, affording the opportunity to study its natural history in relation to its cellular composition. Our hypothesis was that a greater Treg content in first, clinically stable, grade A1 biopsies is associated with a lower risk of CLAD. <h3>Methods</h3> In this retrospective study, we selected clinically stable patients who received a bilateral LTx between 1 Jan 2010 and 18 Dec 2016 with a first episode of A1B0 ACR and who remained CLAD free for at least 5 years (n=16) or who developed CLAD within 2 years (n=9) following LTx. Immunofluorescence was used to quantify CD4+, CD8+ and FOXP3+ cells in transbronchial biopsies (Figure 1A). Separately, CD3+ cells were fluorescently labelled, micro-dissected (Figure 1B) and, using bisulfite conversion and pyrosequencing, the degree of TSDR methylation was determined. <h3>Results</h3> TSDR methylation was slightly lower in the CLAD group as compared to the CLAD-free group (Figure 1C), indicating increased Treg infiltration. Accordingly, the ratio of CD4+FOXP3+ cells to total CD4+ cells was slightly higher in the CLAD group (Figure 1D). These measures were weakly negatively correlated (r² = 0.250, p=0.0152) (Figure 1E). The ratio of CD4+:CD8+ cells was significantly lower in the CLAD group (p=0.0065) (Figure 1F). <h3>Conclusion</h3> Patients who developed CLAD within 2 years of LTx showed no significant difference in Treg, though greater CD8+ T cell, infiltration compared to stable patients. These results suggest that in asymptomatic patients with a first episode of A1 rejection, greater CD8+ T cell content may be indicative of a poorer long-term outlook. Validation in additional patients is now underway.

Evaluation of Mycophenolate Dose Reductions within the First Year After Lung Transplantation and Outcomes

<h3>Purpose</h3> Mycophenolate mofetil (MMF) significantly decreases acute rejection after lung transplant, however, adverse side effects commonly lead to dose reductions (DR) or temporary discontinuations (tDC). The primary aim of this study is to characterize the impact on ACR (acute cellular rejection) rates and to secondarily characterize the incidence and reasons for DR or tDC. <h3>Methods</h3> A single center retrospective chart review was conducted on patients who received a lung transplant between 7/20/16-2/10/19. Patients who died within index hospitalization or did not discharge on MMF were excluded. Severe leukopenia was defined as WBC<3.0 and all mycophenolic acid doses were converted to MMF equivalents. <h3>Results</h3> A total of 106 patients were included (11 patients excluded for death at index hospital admission or were not discharged on MMF). Seventy-eight (73.5%) patients had MMF dose reductions within the first year with a reduction to the lowest average daily dose of 605mg (±241), and leukopenia was the leading indication (76%) (Table 1). Age greater than 65 was significantly associated with higher incidence of severe leukopenia (27/55, 49%) (p=0.043) leading to DR or tDC. <h3>Conclusion</h3> While there is high incidence of MMF DR or tDC within the first year post transplant, there was no associations with ACR or development of DSAs. Older age was associated with more severe leukopenia and may warrant lower target doses without increasing ACR episodes.

Acute rejection and post lung transplant surveillance.

PurposeThe purpose of this review is to summarize the current evidence on the evaluation and treatment of acute rejection after lung transplantation.ResultsDespite significant progress in the field of transplant immunology, acute rejection remains a frequent complication after transplantation. Almost 30% of lung transplant recipients experience at least one episode of acute cellular rejection (ACR) during the first year after transplant. Acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection (AMR) are all risk factors for the subsequent development of chronic lung allograft dysfunction (CLAD). Acute cellular rejection and lymphocytic bronchiolitis have well-defined histopathologic diagnostic criteria and grading. The diagnosis of antibody-mediated rejection after lung transplantation requires a multidisciplinary approach. Antibody-mediated rejection may cause acute allograft failure.ConclusionsAcute rejection is a risk factor for development of chronic rejection. Further investigations are required to better define risk factors, surveillance strategies, and optimal management strategies for acute allograft rejection.

Yield of surveillance endomyocardial biopsies after heart transplantation: a 10-year experience

Abstract Funding Acknowledgements Type of funding sources: None. Background Endomyocardial biopsy (EMB) is recommended as a surveillance procedure for the detection of allograft rejection in all patients after heart transplant. However, the clinical yield of EMB is reported to be low and there are limited evidence in Asian population. Objective The purpose of this study was to investigate the incidence of allograft rejection in after heart transplantation (HT) and yield of surveillance EMB. Method We conducted a retrospective study of consecutive patients who underwent heart transplantation between 2008 and 2017. Of these patients, EMB were classified into surveillance and clinically indicated EMB and were included for analysis. The study assessed EMB results, allograft rejection episodes, and rejection treatments. All patients received induction immunosuppressant and maintaining immunosuppressant regimen including calcineurin inhibitor, mycophenolate, and 6- month tapering off steroid. T-test, Chi-square were used to analyze. Results A total of 622 EMBs of 67 patients were assess. There were 173, 114, 162, 87 and 86 procedures performed during 0-30 days, 31-90 days, 91-365 days, 1-2 year and more than 2 years after HT, respectively. Of these, 560 (90%) EMBs were performed for surveillance. The common reasons for clinically indicated EMB are post anti-rejection treatment (46.8%) and symptoms and signs of rejection (25.8%). Overall, the 2R and 3R episodes of acute cellular rejection were found in 5.5% of EMB results. The clinically indicated EMBs had higher episodes of abnormal EMB result and rejection requiring treatment (53.2% vs 28.1% and 20.1% vs 3.9%, p &amp;lt;0.001 for both) (Table). Conclusion In this single center study, The EMBs in asymptomatic patients had lower likelihood of abnormal result when compared to clinically indicated EMBs. the clinical yield of EMB is comparable with previously reports in developed countries. This is the largest cohort reported from Southeast Asia. Abstract Figure.

Cardiac Transplantation in Danon Disease

Danon disease (DD) is a rare X-linked dominant cardioskeletal myopathy caused by mutations in the lysosome-associated membrane protein-2 (LAMP-2) gene that is usually lethal without cardiac transplantation. The purpose of this study was to characterize post-transplant outcomes in a large cohort of patients with DD who underwent cardiac transplantation. The clinical phenotype and outcome data of patients with DD who underwent cardiac transplantation (n = 38; 19 males and 19 females) were obtained from 8 centers. Study outcomes included graft survival, defined as death or retransplantation, and episodes of acute cellular and antibody-mediated rejection and cardiac allograft vasculopathy at 1 year. Median follow-up time after transplantation for the entire cohort was 4.4 years (IQR: 1.5-12.8 years). The median age at transplant for the cohort was 20.2 years (15.8-27.9 years), with no difference in age between sexes. Median pretransplant left-ventricular ejection fraction for the entire cohort was 30% (range 11%-84%). Males had higher pretransplant aspartate aminotransferase, alanine aminotransferase and creatine phosphokinase levels than females (P < 0.001). There were 2 deaths in the entire cohort and 2 retransplants. There was no difference in actuarial graft survival between males and females (P = 0.8965); the estimated graft survival was 87.1% (95%CI: 63.6%-95.9%) at 5 years. One episode (2.7%) of antibody-mediated rejection, grade 2, and 7 episodes (19%) of acute cellular rejection, grade 2 or 3, were reported in patients who survived to discharge (6 females and 1 male; P = 0.172). Heart transplantation outcomes are acceptable in DD with high probabilities of 5-year graft survival for males and females suggesting that cardiac transplantation is an effective treatment option for DD patients.

Speckle-tracking-based global longitudinal and circumferential strain detect early signs of antibody-mediated rejection in heart transplant patients.

Acute rejection is an important cause of mortality after heart transplant (HTx), but symptoms develop only when myocardial damage is already extensive. We sought to investigate if echocardiographic parameters can detect and predict an acute cellular rejection (ACR) or antibody-mediated rejection (AMR) episode in HTx patients. Data of 403 consecutive HTx recipients between 2003 and 2020 from our centre were reviewed. Patients with severe ACR (n = 10) and AMR (n = 7) were identified. Each HTx patient presenting with rejection was matched to a control HTx patient. Echocardiographic variables from the moment of rejection and 3, 6, and 12 months before were analysed and compared among groups. At acute rejection episode, patients with rejection had lower values of global longitudinal strain (GLS), global circumferential strain (GCS), and left ventricular ejection fraction (LVEF) compared to controls. HTx patients with AMR showed a progressive decline of GLS and GCS in the months preceding acute rejection, while controls and ACR patients had stable strain values except for the moment of rejection. In our cohort, a GLS cut-off lower than 15.5% and a GCS cut-off lower than 15.2% could distinguish with a sensitivity and specificity of 100.0% AMR from controls 3 months before rejection. LVEF and other conventional echo parameters could not differentiate among groups. GLS and GCS show a progressive decrease months before AMR becomes clinically apparent. Our data suggest that global strain assessment by echocardiography allows an early detection of a developing AMR, which could improve the clinical management of HTx patients.

PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation.

PD-L1 (Programmed Death Ligand 1) as a Marker of Acute Cellular Rejection After Heart Transplantation.

Clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients

IntroductionRejection is the most important problem for renal graft function and survival. Complement system plays a key role in immune responses from host to graft. It was demonstrated that complement system activation is related with renal fibrosis. We evaluate clinical impact of complement deposition findings on biopsies in acute rejection episodes of pediatric renal transplant patients. MethodDemographics of the patients, graft functions, acute rejection episodes and graft loss were recorded from data files of 165 pediatric renal transplant patients. Findings of 98 renal biopsies were retrospectively evaluated. ResultsThirty three patients with kidney transplant had 44 acute rejection episodes (32 pure cellular acute rejection episodes / 1 pure humoral acute rejection episode / 11 combined acute cellular and acute humoral rejection episodes) proven by biopsy. C1q staining was positive in 7 biopsies, C3 staining in 15 biopsies and, C4d staining in 15 biopsies. 26 patients had graft fibrosis. All patients with a rejection history had a significant decrease in GFR value during follow-up. Patients who did not have fibrotic changes in first biopsy had same level of deterioration of GFR when compared with patients who had fibrotic changes in first biopsy. ConclusionWe could not demonstrate a significant relation between complement deposition and renal fibrosis, and between complement deposition and GFR values. Our data demonstrated that graft outcomes and graft loss after acute rejection episodes cannot be predicted only with complement deposition on graft or only with graft fibrosis.

Differential cytokine and chemokine expression during rejection and infection following intestinal transplantation

Background/objectivesRejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants. MethodsThis was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel. ResultsOur study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance. ConclusionsTo our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.

Clinical Impact, Reactogenicity, and Immunogenicity After the First CoronaVac Dose in Kidney Transplant Recipients.

Clinical Impact, Reactogenicity, and Immunogenicity After the First CoronaVac Dose in Kidney Transplant Recipients.