Panel Reactive Antibody Levels Research Articles

Immunology Status of Patients During Kidney Transplant.

The immunology status of a patient has a crucial role in kidney transplant. We investigated the effectiveness of a desensitization protocol, guided by the immunology status of patients, for kidney transplant candidates. Antibody screening for human leukocyte antigens was conducted with the Luminex single-antigen microsphere bead assay method for 34 patients from June 2021 to June 2022. Donor human leukocyte antigen genotypes at 8 loci (A*, B*, С*, DRB1*, DQA1*, DQB1*, DPA1*, and DPB1*) were determined, to correlate the specificities of recipient human leukocyte antigen antibodies with donor antigens and identify unacceptable donor antigen combinations. Specialized immunology studies measured panel reactive antibody levels and human leukocyte antigen class I and class II antibodies. A crossmatch compatibility test using complementdependent cytotoxicity was conducted. Of the 34 patients, 10 completed all 3 stages of the desensitization therapy. Most patients experienced decreased sensitization to human leukocyte antigen class I and class II antibodies. Two patients achieved complete clearance of A1 and DQ5 antibodies, respectively, whereas 1 patient exhibited an increase in donor-specific antibody mean fluorescence intensity. Prior to desensitization therapy, the crossmatch compatibility test yielded positive results with T and B lymphocytes. After completing the therapy, the crossmatch test showed negative results in 4 cases with T lymphocytes and positive results with B lymphocytes. Plasmapheresis sessions effectively reduced circulating antibodies. However, the combination of rituximab and plasmapheresis alone did not achieve a negative crossmatch test required for kidney transplant. It is crucial to assess the reduction of donor-specific antibody quantity, considering both the percentage and the mean fluorescence intensity. To avoid false-positive results in crossmatch analysis, drug half-life must be considered. Laboratories should have various crossmatch techniques, such as flow cytometry and single-antigen microsphere bead assay technology, available for research and urgent cases that require crossmatch analysis.

Informing preconception counseling: Outcomes among female heart transplant recipients in the ISHLT registry

The numbers of women of child-bearing age undergoing heart transplantation (HT) and female pediatric HT recipients surviving to child-bearing age have increased, along with improvements in post-transplant survival. Data regarding life expectancy and comorbidities in reproductive-aged female HT recipients are needed to inform shared decision-making at the time of preconception counseling. The International Society for Heart and Lung Transplantation (ISHLT) Thoracic Organ Transplant Registry was investigated for HT recipients between January 1, 2000 and June 30, 2017. Women of childbearing age were defined as those aged 15-45 years, either at transplant, or at the respective post-transplant follow-up. Characteristics and outcomes of female recipients of childbearing age at transplant, 5-, 10-, and 15-year follow-up were compared to females>45 years of age, males 15-45 years and males>45 years of age at the corresponding time intervals. Outcomes included survival, development of diabetes (DM), severe renal dysfunction (CKD), and cardiac allograft vasculopathy (CAV). During the study period, 71,585 HT recipients were included: 24% (n=17,194) were female and 9.2% (n=6602) were of childbearing age at HT. A pre-transplant diagnosis of peripartum cardiomyopathy was associated with significantly worse post-transplant survival, a finding that remained independent of panel reactive antibody levels. The presence of pre-transplant DM and/or severe CKD was significantly associated with lower survival as were the presence of CAV, DM, and CKD post-HT. Knowledge of the impact of pre-existing comorbidities and complications post-HT on survival are important for risk stratification for preconception counseling post-HT.

Effect of serum panel reactive antibodies on allogeneic hematopoietic stem cell transplantation in pediatric thalassemia patients: A single-center experience.

The aim of this study was to assess the impact of serum panel reactive antibodies (PRA) on the outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric thalassemia patients. A total of 73 pediatric patients with thalassemia were included in this single-center study. Pre-transplant PRA levels were evaluated, and the patients were divided into two groups: PRA-negative (group 1; n = 44) and PRA-positive (group 2; n = 29). Patient characteristics, including age, gender, donor type, stem cell source, and HLA compatibility, were analyzed. Transplant outcomes, including engraftment, transfusion requirements, and transplant-related complications, were compared between the two groups. Further subgroup analysis was performed based on MFI values. At the time of transplantation, patients in group 1 were younger than those in group 2 (p = .008). The number of fully matched donors within the family (MSD and MFD) was significantly higher in group 1 (p = .049). Additionally, Rh blood group incompatibility was higher in group 2 (p = .03). There was no statistically significant difference in the engraftment days of neutrophils, platelets, and erythrocytes between the two groups. The frequency of poor graft function and graft failure was higher in the group 2, but there was no statistically significant difference. Post-transplant transfusion requirements for platelets and red blood cells were significantly higher in the group 2 (p < .001). Transplant-related complications such as VOD, PRES, and aGvHD were more common in the group 2, but no statistical significance was detected. Serum PRA in pediatric thalassemia patients may impact the outcomes of HSCT. PRA-positive patients had higher rates of blood product transfusion requirements. Although poor graft function, graft failure, and post-transplant complications were more common in the group 2, statistical significance was not observed. Identifying patients with high PRA levels can assist in optimizing transplant strategies and post-transplant care, leading to improved outcomes for the patients.

Panel reactive antibody level according to history of blood transfusion and pregnancy in kidney transplant candidate

Panel reactive antibody level according to history of blood transfusion and pregnancy in kidney transplant candidate

Prospective randomized controlled trial of the safety and feasibility of a novel mesenchymal precursor cell therapy in hypoplastic left heart syndrome

ObjectiveTo assess the safety and feasibility of low-dose, novel, allogenic mesenchymal precursor cell (MPC) therapy as an adjunct to left ventricular (LV) recruitment for patients with hypoplastic left heart syndrome (HLHS) and borderline left ventricles. MPC injections into the hypoplastic left ventricle may stimulate neovascularization and beneficial LV remodeling and may improve the likelihood of achieving biventricular (BiV) or 1.5 ventricle (1.5V) circulation. MethodsChildren <5 years with prior single ventricle palliation undergoing LV recruitment surgery at a single center were randomized to MPC injections into the LV endocardium/papillary muscles (MPCs) or standard-of-care (controls) and followed for 24 months. The primary endpoint was safety, including (serious) adverse events (S/AEs), and panel reactive antibodies (PRAs). Secondary endpoints included BiV/1.5V conversion and LV size and function. ResultsNineteen subjects were enrolled, including 9 MPC recipients and 10 controls. Fourteen patients (74%) had >1 AE, and 2 patients had SAEs, both deemed unrelated to the trial product. AE severity and frequency were similar in the 2 groups. Baseline PRA levels were high, with no difference between the groups at 12 months. The overall probability of BiV/1.5V conversion was 0.16 (95% confidence interval [CI], 0.05 to 0.41) at 12 months and 0.52 (95% CI, 0.31 to 0.77) at 24 months. For patients with imaging data at both time points, increases in LV volumes from baseline to 12 months were larger in the MPC group by 3-dimensional echocardiography and cardiac magnetic resonance imaging. For children who successfully underwent BiV conversion (n = 12), full BiV conversion was achieved at 24 months in 5 of 5 (100%) MPC-treated children compared with 4 of 7 (57%) controls. ConclusionsMPC injections were considered safe and feasible in HLHS patients. More than 50% of subjects underwent BiV/1.5V conversion within 2 years. Larger trials are needed to investigate the therapeutic potential of MPCs in this population.

#6797 EFFICACY OF DESENSITIZATION TREATMENT IN HYPERIMMUNIZED PATIENTS AWAITING A CADAVERIC KIDNEY TRANSPLANTATION

Abstract Background and Aims On all kidney waiting lists, patients who have antibodies against more than 80% of a panel reactive antibody (PRA) are difficult to transplant, even with national or regional programs. Desensitization treatment with high-dose intravenous immunoglobulin and rituximab could be offered to patients with a long waiting time for a cadaveric donor to improve their odds of finding a kidney. Method Retrospective, single-center study including all hyperimmunized patients on the waiting list for a cadaveric kidney donor who received a desensitization treatment between 2010-2020. To be considered to the desensitization protocol, all the patients must have a PRA above 75% and have been on the waiting list more than 3 years, without any offer. Our treatment was based on the modified Cedars-Sinai Medical Center protocol. Eight hyperimmunized patients on the waiting list for a cadaveric donor kidney transplant (50% male with a mean age of 41.5±16.4 years) received desensitization treatment with intravenous immunoglobulin and Rituximab. Six of the 8 patients (75%) were on renal replacement therapy with hemodialysis and two on peritoneal dialysis (mean time on dialysis 48±14 months). 75% had received a previous transplant. The median PRA calculated was 98%. The time between desensitization and kidney transplantation, the percentage of reactivity against panel cells (PRA) before and after therapy, graft and donor survival, as well as episodes of acute rejection and viral infections were analyzed. The mean follow-up time after transplantation was 67 months. Results No patient presented significant side effects to desensitization treatment. Seven of the 8 patients (87.5%) could be transplanted from a cadaveric donor (negative crossmatch test), in a median 8 months after desensitization. No significant changes were observed in the PRA levels. In the immediate post-transplant period, there were 2 graft losses (28.6%) due to non-immunological causes (1 venous thrombosis in a patient with a coagulation disorder and 1 primary graft failure). Creatinine at discharge was 1.6±0.4 mg/dl and 1.4±0.2 a year after the transplant. Five-year censored death graft survival was 100%. Three patients presented viral replication (1 due to cytomegalovirus (CMV), 1 due to polyomavirus (BK) and another CMV+BK), which became negative after switching to m-Tor therapy. There were no episodes of acute rejection. No patient developed cancer during the follow-up. Conclusion Desensitization treatment with immunoglobulin and rituximab on hyperimmunized patients on the cadaveric waiting list is a safe and effective treatment that increases the chances of achieving a kidney transplant in highly sensitized patients.

Sex-Specific Outcomes of Candidates Listed as the Highest Priority Status for Heart Transplantation.

While sex differences in heart transplantation (HT) waitlist mortality have been previously described, waitlist and HT outcomes by sex of patients in the highest urgency strata (Status 1) since implementation of the 2018 allocation system change in the United States are unknown. We hypothesized that women listed as Status 1 may have worse outcomes due to adverse events on temporary mechanical circulatory support. The analysis included adult, single-organ HT waitlist candidates listed as Status 1 at any time while listed, after the HT allocation system change (from October 18, 2018 through March 31, 2022). The primary outcome was the rate of HT by sex, assessed using multivariable competing risk analysis where waitlist removal for death or clinical deterioration was the competing event. Post-HT survival by sex of waitlist candidates transplanted as a Status 1 was also compared. Of 1120 Status 1 waitlist candidates (23.8% women), women had a lower rate of HT compared to men (adjusted hazard ratio, 0.74 [95% CI, 0.62-0.88]; P<0.001) and a higher rate of delisting for death or medical unsuitability (adjusted hazard ratio, 1.48 [95% CI, 1.05-2.09]; P=0.026). Calculated panel reactive antibody did not account for all the harm observed. Post-HT survival of Status 1 candidates by sex was similar (adjusted hazard ratio, 1.13 [95% CI, 0.62-2.06]; P=0.70). Women have a lower rate of HT and higher rate of delisting for death or clinical deterioration at the highest urgent status, which appears to be mediated but not fully explained by calculated panel reactive antibody levels. Further investigation into the safety profile of temporary mechanical circulatory support devices in women is needed.

Association Between Venous Homografts and Allosensitization After Norwood Procedure.

Right ventricle (RV) to pulmonary artery (PA) shunts have become the shunt of choice at many centers for use during the Norwood procedure for single ventricle palliation. Some centers have begun to use cryopreserved femoral or saphenous venous homografts as an alternative to polytetrafluoroethylene (PTFE) for shunt construction. The immunogenicity of these homografts is unknown, and potential allosensitization could have significant implications on transplant candidacy. All patients undergoing Glenn procedure at our center between 2013 and 2020 were screened. Patients who initially underwent Norwood procedure with either PTFE or venous homograft RV-PA shunt and had available pre-Glenn serum were included in the study. The primary outcome of interest was panel reactive antibody (PRA) level at the time of Glenn surgery. Thirty-six patients met inclusion criteria (N = 28 PTFE, N = 8 homograft). Patients in the homograft group had significantly higher median PRA levels at the time of Glenn surgery (0% [IQR 0-18] PTFE vs 94% [IQR 74-100] homograft, P = .003). There were no other differences between the two groups. Despite potential improvements in PA architecture, the use of venous homografts for RV-PA shunt construction at the time of Norwood procedure is associated with significantly elevated PRA level at the time of Glenn surgery. Centers should carefully consider the use of currently available venous homografts given the high percentage of these patients who may require future transplantation.

DETERMINATION OF THE PRA POSITIVITY PERCENTAGE IN MALE PATIENTS WITH CHRONIC KIDNEY DISEASE BY USING FLOW CYTOMETRY TECHNIQUE.

The antibodies directed against human leukocyte antigen (HLA) molecules, which play a crucial role in allograft histocompatibility, are called anti-HLA antibodies. Anti-HLA antibodies against foreign HLA molecules may be present in patients with chronic kidney disease even before transplantation. The panel reactive antibody (PRA) test is used to measure the renal transplant candidate's immune sensitivity to HLA molecules other than their own HLA molecules by assessing the diversity of anti-HLA antibodies in the blood of these patients. This study aimed to determine the PRA values and the percentage of PRA positivity of Turkish male patients with chronic kidney disease (CKD), who had not been sensitized by the major known causes (those with no history of organ or tissue transplantation, those with no history of blood transfusion), who had not been diagnosed with any autoimmune diseases, and who had not been under immunosuppressive treatment. The study included 60 male patients aged over 18 years. All of the patients were followed up with a diagnosis of CKD at the Nephrology Clinic, Internal Medicine Department, Akdeniz University Medical Faculty Hospital. None of the patients included in the study was sensitized by a known mechanism previously (they did not have blood transfusion or organ transplantation). Glomerular filtration rate (GFR) levels of all patients were below the level of 60 mL/min/1.73 m2. Patient data including their age information, etiology of CKD, accompanying diseases, and information about dialysis modalities were recorded. HLA antibody percentage was determined by the flow cytometry technique. Statistical data analysis was performed by using SPSS 22.0 (Statistical Package for Social Sciences, Version 22.0). The values of p less than 0.05 were considered statistically significant. Twenty patients were receiving dialysis treatment due to end-stage renal disease. Of the 60 patients included in the study, 25% showed PRA positivity; 28.3% of all study patients were found to be positive for anti-HLA class I antibodies and 26.7% of all study patients were found to be positive for anti-HLA class II antibodies on separate analysis for anti-HLA class I and anti-HLA class II antibody positivity. When the patients were categorized as PRA negative and PRA positive in two groups, there were no differences between the groups according to mean age, percentage of hemodialysis patients, percentage of peritoneal dialysis patients and presence of accompanying chronic diseases (such as hypertension, type 2 diabetes mellitus, hyperlipidemia, nephrolithiasis, coronary artery disease). In addition to this, evaluation of the GFR levels showed that the PRA positive group contained a significantly higher percentage of end-stage renal disease patients (GFR <15 mL/min/1.73 m2) as compared with the PRA negative group. Detailed analysis of the percentages of PRA levels in the PRA positive patients, which was carried out to determine the degree of sensitization, showed that the PRA values were over 80% in 11.77% of the patients positive for anti-HLA class I antibodies. On the other hand, PRA values were within the range of 15%-80% in 88.23% of the patients who had anti-HLA class II antibodies. The PRA values were below 80% in all of the patients positive for anti-HLA class II antibodies and those positive for both anti-HLA class I and class II antibodies. In conclusion, PRA levels of the candidates for kidney transplantation should always be measured to assess their state of sensitization before transplantation, even though they have no risk factors known to cause anti-HLA antibody development.

Effect of Maintaining Immunosuppression After Kidney Allograft Failure on Mortality and Retransplantation.

We performed a single-center retrospective study of patients transplanted from October 2007 to May 2017 with AF. We collected data on demographics, immunosuppression, calculated panel reactive antibody (cPRA) levels, death, retransplantation, and dialysis. Cox regression models were used to evaluate factors associated with death and retransplantation. From October 2007 to May 2017, 1354 solitary ABO-compatible transplants were performed, of which 97 failed. Ten percent of patients received a preemptive retransplant. Among those who returned to dialysis (n = 87), 35% died, 25% received another transplant, and 30% remained on dialysis. After AF, 46% of patients discontinued immunosuppression. The cPRA was unchanged if immunosuppression was maintained, but immunosuppression discontinuation was associated with increased cPRA from a median (interquartile range) of 18 (0-99) to 96 (88.5-100.0; P = 0.003). Age at failure (hazard ratio, 1.1; confidence interval, 1.0-1.1) and cardiovascular disease were associated with death (hazard ratio, 2.9; confidence interval, 1.2-7.0) in multivariate analysis. Importantly, immunosuppression maintenance was not associated with increased death or retransplantation despite the increase in cPRA that occurred when immunosuppression was discontinued. Kidney transplant recipients with AF have a high mortality rate after dialysis initiation. Although immunosuppression withdrawal was associated with increased cPRA, it was not associated with reduced retransplantation. Therefore, it is reasonable to discontinue immunosuppression after AF despite sensitization if retransplantation is delayed.

Abstract 14413: Possible Antibody Mediated Cardiac Rejection After Combined Heart-Kidney Transplant in a Sensitized Patient Associated to COVID-19 Pneumonia

Background: Antibody mediated rejection (AMR) starts with the appearance of donor-specific antibodies (DSA), followed by graft injury that may be subclinical and can progress to cardiac allograft vasculopathy (CAV) and chronic graft dysfunction. Case report A 48-year-old man with a past medical history of right nephrectomy due to congenital renal atrophy and dilated cardiomyopathy required heart transplantation at age 31, presented an episode of AMR grade 2 ten years post-transplant developing CAV with graft loss and end-stage renal disease. He was listed for a combined heart-kidney transplant. His panel reactive antibody (PRA) level was 40%, requiring desensitization therapy (plasmapheresis, intravenous gamma globulin and rituximab). At age 44, he received a heart-kidney transplant. Methylprednisolone and rabbit antithymocyte globulin were used for induction and desensitization therapy with plasmapheresis and intravenous gamma globulin at months 0-3-6-12 was continued. Maintenance immunosuppression therapy continued with tacrolimus, mycophenolic acid and prednisone. During follow-up persistent circulating DSA anti-class II HLA were detected and PRA reached 80%. He was admitted with a multifocal COVID-19 pneumonia. He had received 4 doses of the messenger RNA vaccine BNT162b2. Dexamethasone was started and mycophenolic acid was discontinued for 14 days. He did not need mechanical ventilation. Echocardiogram revealed marked concentric LVH, LVEF = 60%, grade II diastolic dysfunction and reduced global longitudinal strain (-7,6%). Pro-BNP was 962 pg/ml, and Troponin T 100 pg/ml. Endomyocardial biopsy showed no signs of cellular rejection nor capillary injury. Immunopathologic findings were negative. Coronary angiogram showed no significant lesions. AMR was suspected, the patient was treated with methylprednisolone, plasmapheresis and intravenous gamma globulin. Clinical response was satisfactory, and he was discharged in functional class I (NYHA). Conclusions Although both histological and immunopathologic studies were negative, clinical suspicion for AMR in a highly sensitized patient prevailed in the context of a recent infectious intercurrence. Other diagnosis cannot be completely ruled out in this clinical scenario.

Pig heart and lung xenotransplantation: Present status.

The recent pig heart transplant in a patient at the University of Maryland Medical Center has stimulated renewed interest in the xenotransplantation of organs from genetically engineered pigs. The barriers to the use of pigs as sources of organs have largely been overcome by 2 approaches - (1) the deletion of expression of the three known pig carbohydrate xenoantigens against which humans have preformed antibodies, and (2) the transgenic introduction of human 'protective' proteins, such as complement-regulatory proteins. These gene modifications, coupled with immunosuppressive therapy based on blockade of the CD40/CD154 costimulation pathway, have resulted in survival of baboons with life-supporting pig heart grafts for almost 9 months. The initial clinical success at the University of Maryland reinforces encouraging preclinical results. It suggests that pig hearts are likely to provide an effective bridge to an allotransplant, but their utility for destination therapy remains uncertain. Because of additional complex immunobiological problems, the same approach has been less successful in preclinical lung xenograft transplantation, where survival is still measured in days or weeks. The first formal clinical trials of pig heart transplantation may include patients who do not have access to an allotransplant, those with contraindications for mechanical circulatory support, those in need of retransplantation or with a high level of panel-reactive antibodies. Infants with complex congenital heart disease, should also be considered.

Misidentification of preformed anti-HLA-DP antibodies leads to antibody-mediated kidney transplant rejection: a case report

BackgroundPatients who are HLA-sensitized are at high risk for early antibody-mediated rejection (AMR) and worse outcomes. Therefore, it is crucial to detect the presence of donor-specific antibodies (DSAs) using pretransplant antibody identification and crossmatch assays. An error in antibody identification can lead to disastrous clinical outcomes. We present a case of acute AMR associated with preformed HLA-DPα and HLA-DPβ DSAs that were not identified before transplantation.Case presentationA 27-year-old woman received a second kidney transplant from a deceased donor. Her pretransplant panel-reactive antibody level was 94%. The complement-dependent cytotoxicity crossmatch was negative for T and B cells at the time of transplantation. She experienced early acute AMR proven by a kidney biopsy. Single antigen bead testing of the patient’s serum at the time of rejection as well as the pre-second transplant serum revealed strong antibodies against the DPA1*01:03 and DPB1*02:01 alleles in the second donor. These antibodies were not identified by phenotypic bead assay during the patient’s time on the waiting list. The patient was treated with plasmapheresis and anti-thymocyte globulin. However, she experienced abdominal pain on day 37 post-transplantation. Surgical exploration revealed a laceration on the transplanted kidney, which was then repaired. Subsequently, infected hematoma was suspected and the transplanted kidney was removed.ConclusionThe present case highlights the clinical significance of preformed HLA-DPα and HLA-DPβ DSAs. Accuracy in determination of HLA antibodies before transplantattion is critical for transplant outcome. HLA-DP typing and single antigen bead testing are recommended for a precise antibody interpretation, especially in highly sensitized patients. Careful interpretation of antibody testing results is essential for the success of organ transplantation.

Efficacy and safety of combination of ulinastatin and meglumine cyclic adenosine monophosphate in the treatment of acute myocardial infarction, and its effect on serum levels of hs-CRP, cTnI and CK

Purpose: To determine the efficacy and safety of a combination of ulinastatin and meglumine cyclic adenosine monophosphate (cAMP) in the treatment of acute myocardial infarction (AMI), and its effect on serum levels of hypersensitive-c-reactive protein (hs-CRP), cardiac troponin I (cTnI), creatine kinase (CK).Methods: A total of 90 AMI patients admitted to The Second Affiliated Hospital of Qiqihar Medical College, Qiqihar City, Heilongjiang Province, China from January 2019 to January 2020 were selected and randomized (in a 1:1 ration) into control group and study group. Patients in the two groups received meglumine cAMP, while those in the study group were, in addition, treated with ulinastatin. The two groups were compared with regard to clinical efficacy, cardiac function indices, serum biochemical indices, incidence of drug-related side effects, duration and number of episodes of angina pectoris, and levels of neuroendocrine hormones.Results: The study group exhibited remarkably higher treatment effectiveness and cardiac function indices compared to the control group (p &lt; 0.05). However, lower levels of serum biochemical indices, lower total incidence of drug toxicity, smaller number and shorter duration of angina pectoris, and lower levels of panel reactive antibodies (PRA) were observed in the study when compared to control group (p&lt; 0.001).Conclusion: Treatment of AMI patients with the combination of ulinastatin and meglumine cAMP significantly reduces the clinical symptoms of the patients, with remarkable efficacy and high safety. Furthermore, it down-regulates serum levels of hs-CRP, cTnI and CK. Thus, the combination treatment seems superior to the conventional therapy.

The role of sensitization in post-transplant outcomes in adults with congenital heart disease sensitization in adults with congenital heart disease

IntroductionThe number of heart transplants in adults with congenital heart disease (CHD) is increasing, though outcomes remain unfavorable compared to those without CHD. The etiology of this mortality difference remains uncertain. Panel reactive antibody (PRA) is a predictor of survival post-transplantation, and adult CHD patients have been observed to have higher PRA levels. Here we assessed the relationship between PRA and outcomes in adult patients with CHD who underwent heart transplantation. MethodsThis is a retrospective cohort study using the 2004–2015 ISHLT Thoracic Organ Transplant Registry to investigate the role of sensitization in the observed excess mortality. The composite outcome of mortality or graft failure within 1-year of transplantation was compared among CHD vs. non-CHD recipients, according to sensitization as measured by pre-transplant panel reactive antibodies (PRA). ResultsAdults with CHD (n = 1188) had higher PRA level compared to non-CHD (n = 38,201) recipients (27% vs. 18% PRA>10%, respectively, p < 0.001). CHD diagnosis remained independently associated with a higher incidence of the composite outcome in multivariable analysis after adjusting for PRA and other variables. Further, even after age-matching, patients with CHD and PRA ≤10% were at higher risk of the primary outcome compared to non-CHD (OR 2.1 [1.4–3.4], p = 0.001), though both groups had comparable outcomes when PRA was >10% (OR 1.1 [0.6–2.0], p = 0.852). ConclusionsAdults with CHD are more likely to have higher sensitization and worse outcomes than non-CHD recipients. Higher sensitization rates alone do not fully explain their excess risk of adverse outcomes after heart transplantation.

Incidence of acute rejection and patient survival in combined heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is indicated for patients with concomitant end-stage heart and liver disease or patients with amyloid heart disease where liver transplantation mitigates progression. Limited data suggest that the liver allograft provides immunoprotection for heart and kidney allografts in combined transplantation from the same donor. We hypothesized that CHLT reduces the incidence of acute cellular rejection (ACR) and the development of de novo donor-specific antibodies (DSAs) compared with heart-alone transplantation (HA). We conducted a retrospective analysis of 32 CHLT and 280 HA recipients in a single-center experience. The primary outcome was incidence of ACR based on protocol and for-cause myocardial biopsy. Rejection was graded by the International Society of Heart and Lung Transplantation guidelines with Grade 2R and higher considered significant. Secondary outcomes included the development of new DSAs, cardiac function, and patient and cardiac graft survival rates. Of CHLT patients, 9.7% had ACR compared with 45.3% of HA patients (p<0.01). Mean pretransplant calculated panel reactive antibody (cPRA) levels were similar between groups (CHLT 9.4% vs. HA 9.5%; p=0.97). Among patients who underwent testing, 26.9% of the CHLT and 16.7% of HA developed DSA (p=0.19). Despite the difference in ACR, patient and cardiac graft survival rates were similar at 5years (CHLT 82.1% vs. HA 80.9% [p=0.73]; CHLT 82.1% vs. HA 80.9% [p=0.73]). CHLT reduced the incidence of ACR in the cardiac allograft, suggesting that the liver offers immunoprotection against cellular mechanisms of rejection without significant impacts on patient and cardiac graft survival rates. CHLT did not reduce the incidence of de novo DSA, possibly portending similar long-term survival among cardiac allografts in CHLT and HA.

Panel-Reactive Antibody Associated with Acute Rejection Episodes After Heart Transplantation: An Analysis of the UNOS Database

<h3>Purpose</h3> The presence of circulating alloantibodies can prolong transplant waiting times and may be associated with worse post-transplant outcomes. Recently, patients undergoing heart transplantation have been found to possess higher panel reactive antibody (PRA) levels, but the impact of this finding is uncertain. We aimed to determine the association between an elevated PRA and subsequent episodes of acute rejection. <h3>Methods</h3> Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research Database, we retrospectively reviewed HTs performed from January 2004 to September 2020. Multi-organ transplants and re-transplants were excluded from analysis. Site-reported "Most recent PRA Class I" and "Most Recent PRA Class II" were used to assess PRA level, and the "Acute Rejection Episodes" variable was used to identify acute rejection, regardless of use of anti-rejection therapies. Detection methodology between centers could vary. Patients were stratified into three groups: 1) No-PRA (PRA% = 0), 2) Some-PRA (PRA% >0 and <50), and 3) High-PRA (PRA% >50). Rates of acute rejection were compared by log-rank test, with multivariate analysis adjusting for clinically relevant factors. <h3>Results</h3> A total of 41,537 patients were included in this study. Approximately 19% of patients experienced at least one acute rejection event. When stratifying based on Most Recent PRA Class I, the Some-PRA and High-PRA groups had significantly higher rates of acute rejection episodes, OR 1.22 (95% CI 1.12-1.33, p <0.001) and OR 1.79 (95% CI 1.55-2.06, p <0.001), respectively. Similar findings were obtained when using Most Recent PRA Class II, OR 1.31, (95% CI 1.19-1.45, p <0.001) and OR 1.71 (95% CI 1.47-1.99, p <0.001), respectively. When adjusting for sex and pre-operative blood transfusions, the results remained generally consistent - Class I: OR 3.9 (95% CI 1.04-17, p <0.05) and OR 3.2 (95% CI 0.13-37, p = 0.38), respectively; Class II: OR 3.79 (95% CI 0.94-17, p = 0.065) and OR 18.58 (95% CI 1.42-467, p <0.05), respectively. <h3>Conclusion</h3> Elevated PRA levels are associated with acute rejection episodes after HT, irrespective of patient sex and pre-operative blood transfusions. Further research should be conducted to verify our findings prospectively and account for possible confounders.

Risk Factors of Rejection in Renal Transplant Recipients: A Narrative Review.

Multiple factors influence graft rejection after kidney transplantation. Pre-operative factors affecting graft function and survival include donor and recipient characteristics such as age, gender, race, and immunologic compatibility. In addition, several peri- and post-operative parameters affect graft function and rejection, such as cold and warm ischemia times, and post-operative immunosuppressive treatment. Exposure to non-self-human leucocyte antigens (HLAs) prior to transplantation up-regulates the recipient’s immune system. A higher rate of acute rejection is observed in transplant recipients with a history of pregnancies or significant exposure to blood products because these patients have higher panel reactive antibody (PRA) levels. Identifying these risk factors will help physicians to reduce the risk of allograft rejection, thereby promoting graft survival. In the current review, we summarize the existing literature on donor- and recipient-related risk factors of graft rejection and graft loss following kidney transplantation.

Post-transplantation outcomes of sensitized patients receiving durable mechanical circulatory support

Sensitization, defined as the presence of circulating antibodies, presents challenges, particularly in patients undergoing heart transplantation (HTx) bridged with durable mechanical circulatory support (MCS). We aimed to investigate the post-transplantation outcomes of sensitized MCS patients.Among 889 consecutively enrolled heart transplant (HTx) recipients between 2010 and 2018, 86 (9.7%) sensitized MCS patients (Group A) were compared with sensitized non-MCS patients (Group B, n = 189), non-sensitized MCS patients (Group C, n = 162), and non-sensitized non-MCS patients (Group D, n = 452) regarding post-HTx outcomes, including the incidence of primary graft dysfunction (PGD), 1-year survival, and 1-year freedom from antibody-mediated rejection (AMR).Sensitized MCS patients (Group A) showed comparable rates of PGD, 1-year survival, and 1-year freedom from AMR with Groups C and D. However, Group A showed significantly higher rates of 1-year freedom from AMR (95.3% vs 85.7%, p = 0.02) and an earlier decline in panel-reactive antibody (PRA) levels (p < 0.01) than sensitized non-MCS patients (Group B). Desensitization therapy effectively reduced the levels of PRA in both Groups A and B. When Group A was further divided according to the presence of preformed donor-specific antibodies (DSA), patients with preformed DSA showed significantly lower rates of 1-year freedom from AMR than those without (84.2% vs 98.5%, p = 0.01).Sensitized MCS patients showed significantly lower rates of AMR and an earlier decline in PRA levels following HTx than sensitized non-MCS patients. Removal of MCS at the time of transplantation might underlie these observations.

Arteriovenous Fistula Nonmaturation: What's the Immune System Got to Do with It?

Arteriovenous fistula (AVF) nonmaturation is a persistent problem, particularly among female and Black patients. Increasingly, the immune system has been recognized as an important contributor to vascular disease, but few studies have examined immune factors relative to AVF maturation outcomes. This study evaluated the association of serum panel reactive antibodies (PRA), a measure of immune system reactivity assessed in patients undergoing kidney transplant evaluation, with AVF nonmaturation. We identified 132 patients at our institution who underwent surgical AVF placement between 2010-2019 and had PRA testing within 1 year of AVF creation. Multivariable logistic regression was used to determine the association of patient demographic and clinical factors, class I and class II PRA levels, and preoperative arterial and venous diameters with AVF maturation outcomes. AVF nonmaturation was more likely in females than males (44% versus 20%, P=0.003) and in Black than white patients (40% versus 13%, P=0.001). Class II PRA was higher in females than males (12%±23% versus 4%±13%, P=0.02). In the multivariable model, AVF nonmaturation was associated with class II PRA (adjusted odds ratio [aOR], 1.34 per 10% increase; 95% confidence interval [95% CI], 1.04 to 1.82, P=0.02) and Black race (aOR, 3.34; 95% CI, 1.02 to 10.89, P=0.03), but not with patient sex or preoperative arterial or venous diameters. The association of elevated class II PRA with AVF nonmaturation suggests the immune system may play a role in AVF maturation outcomes, especially among female patients.