Preexisting Donor-specific Antibodies Research Articles

The impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney: A retrospective cohort study

IntroductionThe preoperative examination of kidney transplantation includes HLA antibody screening to initially determine the presence of preexisting donor-specific antibody (DSA) that mediates hyperacute rejection. Recipients with positive HLA antibodies require further HLA specificity analysis to type the antigen and determine the antigen mismatches between the donor and recipient. However, recipients with suspected antibodies would have no further HLA specificity analysis. It is unclear whether suspected HLA antibodies would affect renal graft function. This study aimed to explore the impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney and thus determine the necessity of routinely performing the HLA specificity analysis in recipients with suspected HLA antibodies preoperatively. MethodsThis is a single-center retrospective cohort study. 179 kidney transplant recipients (KTRs) were included and further divided into HLA antibody-negative group (Group 1) and HLA antibody-suspected groups (Group 2) based on the result of the pretransplant HLA antibody screen test. And the antibody-suspected group was further divided into a low-mismatched group (Group A) and a high-mismatched group (Group B) according to the HLA specificity analysis. We tracked the renal function indexes, biochemical indexes, and posttransplant adverse events within 5 years after transplantation and explored the necessity of further HLA specificity analysis in recipients with pretransplant suspected HLA antibodies. ResultsThere was no statistically significant difference in demographics between HLA antibody-negative group and HLA antibody-suspected groups. At 5 years of follow-up, the KTRs in HLA antibody-negative group had significantly higher eGFR levels, lower serum creatinine levels, and less urinary protein compared to those in antibody-suspected group. Meanwhile, the KTRs in low-mismatched group also had significantly higher eGFR levels, lower serum creatinine levels, and less proteinuria compared to those in high-mismatched group. Correlation analysis showed that the age of KTRs, urinary protein levels and the load capacity of HLA mismatches were associated with eGFR levels of KTRs at 5 year posttransplant. ConclusionKTRs with suspected HLA antibodies before kidney transplantation have worse graft function than the preoperative HLA antibody-negative recipients in the long-term posttransplant follow-up. The specific load capacity of HLA mismatches, the age of the recipient and the urinary protein was found to be negatively correlated with long-term posttransplant renal outcomes. It is necessary to undergo further HLA specificity analysis for recipients with suspected HLA antibodies in HLA antibody screen test to explicit HLA mismatches and improve long-term posttransplant outcomes.

Sudden cardiac death after heart transplantation: a population-based study.

The epidemiology of sudden cardiac death (SCD) after heart transplantation (HTx) remains imprecisely described. We aimed to assess the incidence and determinants of SCD in a large cohort of HTx recipients, compared with the general population. Consecutive HTx recipients (n = 1246, 2 centres) transplanted between 2004 and 2016 were included. We prospectively assessed clinical, biological, pathologic, and functional parameters. SCD was centrally adjudicated. We compared the SCD incidence beyond the first year post-transplant in this cohort with that observed in the general population of the same geographic area (registry carried out by the same group of investigators; n = 19 706 SCD). We performed a competing risk multivariate Cox model to identify variables associated with SCD. The annual incidence of SCD was 12.5 per 1,000 person-years [95% confidence interval (CI), 9.7-15.9] in the HTx recipients cohort compared with 0.54 per 1,000 person-years (95% CI, 0.53-0.55) in the general population (P < 0.001). The risk of SCD was markedly elevated among the youngest HTx recipients with standardized mortality ratios for SCD up to 837 for recipients ≤30 years. Beyond the first year, SCD was the leading cause of death. Five variables were independently associated with SCD: older donor age (P = 0.003), younger recipient age (P = 0.001) and ethnicity (P = 0.034), pre-existing donor-specific antibodies (P = 0.009), and last left ventricular ejection fraction (P = 0.048). HTx recipients, particularly the youngest, were at very high risk of SCD compared with the general population. The consideration of specific risk factors may help identify high-risk subgroups.

A Case of Chronic Active Antibody-Mediated Rejection Caused by a Pre-Existing Anti-DQ Donor-Specific Antibody in a Systemic Lupus Erythematosus Recipient Without History of Sensitization: A Case Report

Systemic lupus erythematosus (SLE) is reported to produce anti-HLA antibodies. We report a case of chronic active antibody-mediated rejection caused by pre-existing donor-specific antibody (DSA) in a patient with SLE without a history of sensitization. The case was a 29-year-old man with end-stage renal disease due to lupus nephritis. Cross-match with the mother was negative, but low titer anti-DQ DSA was detected, although he had no prior history of sensitization. After desensitization with rituximab and mycophenolate mofetil, a living donor kidney transplant was undergone, and his early postoperative period was uneventful. However, his renal function started to decline at 2 years post-transplant. Although there was no rejection on the biopsy at 2.5 years post-transplant, his renal function continued to decline after that. At 7 years, he had failed his graft due to chronic active antibody-mediated rejection. Retrospective analysis of human leukocyte antigen antibody tests revealed that anti-DQ DSA had disappeared at 1 year post-transplant, but high titer DSA was detected again with complement-binding capacity at 2 years and after that. Careful monitoring might be warranted in an SLE patient with pre-existing DSA, even though the titer was low and without any prior histories of sensitization events.

Both donor specific and non-donor specific HLA antibodies reduced in recipients post simultaneous liver/kidney transplant

It has been suggested that the liver allograft can protect the kidney allograft from antibody mediated rejection in simultaneous liver/kidney transplant (SLK) recipients by reducing preexisting donor specific antibodies (DSA) via adsorption of DSA by the liver allograft. Recently, the SLK allocation system was altered to provide a kidney safety net to those who do not recover native kidney function after liver transplant. However, the kidney transplant under the safety net creates a theoretical challenge for sensitized patients as the liver graft may not be able to adsorb human leukocyte antigen (HLA) antibodies against the kidney under the safety net because the liver and kidney grafts are from different donors and may carry different HLA antigens. This prompts us to examine levels of non-donor specific HLA antibodies in SLK recipients in our hospital. We found that levels of both DSA and non-DSA decreased post SLK transplant. The presence of preexisting DSA was also not associated with kidney graft survival and antibody mediated rejection in SLK recipients. Our results indicate that the liver transplant can reduce non-DSA, which may increase the pool of compatible kidneys offered under the safety net program for sensitized patients.

COVID-19 in orthotopic heart transplant recipients and association with donor specific antibodies

De novo donor-specific antibodies (DSAs) are associated with increased risk of antibody-mediated rejection and worse clinical outcomes after orthotopic heart transplant (OHT). No study has reported the production of DSAs after infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in an OHT population.In this retrospective study, we described coronavirus disease 2019 (COVID-19) incidence and clinical course in a large, contemporary OHT cohort. We showed that the case-fatality rate has significantly decreased since the early days of the pandemic, although remains higher than that of the general population. In addition, we found that 10% of OHT recipients developed de novo DSAs or experienced an increase in pre-existing DSAs after COVID-19, with the majority occurring in unvaccinated patients (15% vs 2%). Further studies are necessary to substantiate our findings in an external cohort.

Isolated Pre-existing HLA-DP Donor-Specific Antibodies are Associated With Poorer Outcomes in Renal Transplantation

IntroductionThe importance of donor-specific antibodies (DSAs) in renal transplantation has long been recognized, but the significance of human leukocyte antigen (HLA)-DP antibodies remains less clear. We performed a retrospective single center study of renal transplants with pre-existing isolated HLA-DP-DSAs to assess clinical outcomes.MethodsTwenty-three patients with isolated HLA-DP-DSAs were compared with 3 control groups as follows: standard immunological risk (calculated reaction frequency [cRF] < 85%, no current or historical DSA, no repeat mismatched antigens with previous transplants, n = 46), highly sensitized (cRF > 85%, n = 27), and patients with HLA-DP antibodies that were not donor-specific (n = 18). Univariate and multivariate analyses were performed comparing antibody-mediated rejection (ABMR)-free and graft survival. Factors in the final multivariable models included patient group, % cRF, B-cell flow crossmatch (BFXM) positivity and regrafts.ResultsOver a median follow-up of 1197 days, 65% of HLA-DP-DSA patients had ABMR on indication biopsies, and 30% of HLA-DP-DSA patients lost their graft. Pre-existing HLA-DP DSAs remained the single factor associated with ABMR after multivariable analysis (hazard ratio [HR] = 9.578, P = 0.012). Patients with HLA-DP DSAs had increased microvascular scores (P = 0.0346) and worse transplant glomerulopathy (P = 0.015) on biopsy compared with the standard immunological risk group. Furthermore, flow crossmatch (FXM) positivity did not help inform on the risk of graft failure or ABMR in patients with preformed DP-DSA.ConclusionTransplants with pre-existing HLA-DP-DSAs should be considered high risk. Routine laboratory tests are unable to further risk stratify these patients. Recipients should be considered for intensified immunosuppression and closely monitored.

COVID-19 Vaccination and Remdesivir are Associated With Protection From New or Increased Levels of Donor-Specific Antibodies Among Kidney Transplant Recipients Hospitalized With COVID-19.

Alloimmune responses in kidney transplant (KT) patients previously hospitalized with COVID-19 are understudied. We analyzed a cohort of 112 kidney transplant recipients who were hospitalized following a positive SARS-CoV-2 test result during the first 20 months of the COVID-19 pandemic. We found a cumulative incidence of 17% for the development of new donor-specific antibodies (DSA) or increased levels of pre-existing DSA in hospitalized SARS-CoV-2-infected KT patients. This risk extended 8 months post-infection. These changes in DSA status were associated with late allograft dysfunction. Risk factors for new or increased DSA responses in this KT patient cohort included the presence of circulating DSA pre-COVID-19 diagnosis and time post-transplantation. COVID-19 vaccination prior to infection and remdesivir administration during infection were each associated with decreased likelihood of developing a new or increased DSA response. These data show that new or enhanced DSA responses frequently occur among KT patients requiring admission with COVID-19 and suggest that surveillance, vaccination, and antiviral therapies may be important tools to prevent alloimmunity in these individuals.

Occurrence of De novo Donor-Specific Antibodies After COVID-19 in Kidney Transplant Recipients Is Low Despite Immunosuppression Modulation

IntroductionDecreased immunosuppression has been proposed for kidney transplant recipients infected with coronavirus disease 2019 (COVID-19), but the impact on the alloreactive immune response during and after infection has been poorly investigated. We evaluated the occurrence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSAs) (post–COVID-19) and rejection episodes after COVID-19 with particular focus on immunosuppression modulation.MethodsKidney transplant recipients from 2 French institutions had anti-HLA antibody screening before and after COVID-19. Management of immunosuppression, rejection episodes, COVID-19 severity, inflammatory markers, and antiviral therapies were recorded.ResultsFrom 251 recruited patients, 72 were excluded because of COVID-19–related death (n = 25) and incomplete immunologic follow-up (n = 47). Among the remaining 179 included patients, almost half were hospitalized (49.2%). Antimetabolites were interrupted in 47% of patients (82% in hospitalized, median time of resumption of 23 days and in 15% nonhospitalized, median time of resumption of 7 days). Calcineurin inhibitors were interrupted in 12% of patients (all hospitalized, median time of resumption of 11 days). The incidence of post–COVID-19 DSA was 4% (8% and 0% in hospitalized and nonhospitalized, respectively). Allograft rejection occurred in 3 patients (1.7%) and all were hospitalized. Younger age, transplantation <1 year, and preexisting DSA were more frequently observed in patients with post–COVID-19 DSA, whereas inflammatory markers, lymphopenia, and use of antiviral therapies were not.ConclusionThe incidence of post–COVID-19 DSA among COVID-19–positive kidney transplant recipients was low (4%) despite a significant decrease in immunosuppression and was mainly restricted to high-risk immunologic patient’s status. COVID-19 severity was not associated with post–COVID-19 DSA and/or rejection.

Sensitization and Desensitization in Vascularized Composite Allotransplantation.

Vascularized composite allotransplantation (VCA) is a field under research and has emerged as an alternative option for the repair of severe disfiguring defects that result from severe tissue loss in a selected group of patients. Lifelong immunosuppressive therapy, immunosuppression associated complications, and the effects of the host immune response in the graft are major concerns in this type of quality-of-life transplant. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody (DSA) formation and graft rejection in the context of VCA still remain poorly understood. The most common antigenic target of preexisting alloantibodies are MHC mismatches, though recognition of ABO incompatible antigens, minor histocompatibility complexes and endothelial cells has also been shown to contribute to rejection. Mechanistically, alloantibody-mediated tissue damage occurs primarily through complement fixation as well as through antibody-dependent cellular toxicity. If DSA exist, activation of complement and coagulation cascades can result in vascular thrombosis and infarction and thus rejection and graft loss. Both preexisting DSA but especially de-novo DSA are currently considered as main contributors to late allograft injury and graft failure. Desensitization protocols are currently being developed for VCA, mainly including removal of alloantibodies whereas treatment of established antibody-mediated rejection is achieved through high dose intravenous immunoglobulins. The long-term efficacy of such therapies in sensitized VCA recipients is currently unknown. The current evidence base for sensitizing events and outcomes in reconstructive transplantation is limited. However, current data show that VCA transplantation has been performed in the setting of HLA-sensitization.

Kidney transplantation in highly sensitized recipients.

In kidney transplantation (KT), overcoming donor shortage is particularly challenging in patients with preexisting donor-specific antibodies (DSAs) against human leukocyte antigen (HLA), called HLA-incompatible KT (HLAi KT), carrying the risk of rejection and allograft loss. Thus, it is necessary to accurately evaluate the degree of sensitization before HLAi KT, and undertake appropriate pretreatment strategies. To determine the degree of sensitization, complement-dependent cytotoxicity has been the only method employed; the development of a method using flow cytometry further improved the test sensitivity. However, these tests present disadvantages, including the need for living cells, with a solid-phase assay developed to resolve this problem. Currently, the method using Luminex (Luminex Corp.) is widely used in clinical practice. As this method measures DSAs using single antigen beads, it is possible to classify immunological risks by measuring the type and amount of DSAs. Furthermore, there have been major advances in methods that involve DSA removal before HLAi KT. In the early stages of desensitization, plasmapheresis and intravenous immunoglobulins were the main treatment methods employed; however, the introduction of CD20 monoclonal antibody and proteasome inhibitors further increased the success rate of desensitization. Currently, HLAi KT has been established as an important transplant method, but an understanding of DSAs and a novel desensitization treatment are warranted.

Delayed graft function and acute rejection following HLA-incompatible living donor kidney transplantation.

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR=1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction>.1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF=1.45 2.093.02 ; PFNC=1.67 2.403.46 ; PCC=1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction=.1), its impact on DCGF risk was less consequential for ILDKT (aHR=1.34 1.621.95 ) than CLDKT (aHR=1.96 2.292.67 ) (p interaction=.004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.

Guiding therapeutic plasma exchange for antibody-mediated rejection treatment in lung transplant recipients - a retrospective study.

Antibody-Mediated Rejection (AMR) due to donor-specific antibodies (DSA) is associated with poor outcomes after lung transplantation. Currently, there are no guidelines regarding the selection of treatment protocols. We studied how DSA characteristics including titers, C1q, and mean fluorescence intensity (MFI) values in undiluted and diluted sera may predict a response to therapeutic plasma exchange (TPE) and inform patient prognosis after treatment. Among 357 patients consecutively transplanted without detectable pre-existing DSAs between 01/01/16 and 12/31/18, 10 patients were treated with a standardized protocol of five TPE sessions with IVIG. Based on DSA characteristics after treatment, all patients were divided into three groups as responders, partial responders, and nonresponders. Kaplan-Meier Survival analyses showed a statistically significant difference in patient survival between those groups (P=0.0104). Statistical analyses showed that MFI in pre-TPE 1:16 diluted sera was predictive of a response to standardized protocol (R2 =0.9182) and patient survival (P=0.0098). Patients predicted to be nonresponders who underwent treatment with a more aggressive protocol of eight TPE sessions with IVIG and bortezomib showed improvements in treatment response (P=0.0074) and patient survival (P=0.0253). Dilutions may guide clinicians as to which patients would be expected to respond to a standards protocol or require more aggressive treatment.

Crossing low/moderate-level donor-specific antibodies during heart transplantation.

Donor-specific antibodies (DSAs) in patients prior to heart transplantation are associated with increased risk of rejection and can lead to longer waitlist times, but it is not known whether patients with low/moderate-level DSA at transplant have acceptable post-transplant outcomes. We performed a single-center, retrospective review to examine outcomes associated with crossing pre-existing low/moderate-level DSA. We assessed 864 patients awaiting heart transplantation between 2010 and 2018, identified 67 patients with low/moderate-level DSA and compared them to patients who were sensitized without DSA at the time of heart transplantation, as well as a control group of non-sensitized patients. Outcomes included 3-year survival, freedom from cardiac allograft vasculopathy (CAV), freedom from non-fatal major adverse cardiac events (NF-MACE), and 1-year freedom from rejection. In the first-year post-transplant, there was decreased freedom from antibody-mediated rejection (AMR) in the patients with pre-existing DSA compared with patients sensitized without DSA and non-sensitized patients. However, the DSA group experienced similar 3-year post-transplant survival, freedom from CAV, and freedom from NF-MACE compared with the other study groups. Our findings suggest that crossing low/moderate-level DSA does not lead to worse outcomes in heart transplantation and may offer a viable way to increase a sensitized patient's chance to obtain a suitable donor.

The Problem of Subclinical Antibody-mediated Rejection in Kidney Transplantation.

Defined as histologic evidence of rejection on a protocol biopsy in the absence of kidney dysfunction, subclinical rejection has garnered attention since the 1990s. The major focus of much of this research, however, has been subclinical T cell-mediated rejection (TCMR). Herein, we review the literature on subclinical antibody-mediated rejection (AMR), which may occur with either preexisting donor-specific antibodies (DSA) or upon the development of de novo DSA (dnDSA). In both situations, subsequent kidney function and graft survival are compromised. Thus, we recommend protocol biopsy routinely within the first year with preexisting DSA and at the initial detection of dnDSA. In those with positive biopsies, baseline immunosuppression should be maximized, any associated TCMR treated, and adherence stressed, but it remains uncertain if antibody-reduction treatment should be initiated. Less invasive testing of blood for donor DNA or gene profiling may have a role in follow-up of those with negative initial biopsies. If a protocol biopsy is positive in the absence of detectable HLA-DSA, it also remains to be determined whether non-HLA-DSA should be screened for either in particular or on a genome-wide basis and how these patients should be treated. Randomized controlled trials are clearly needed.

The Natural History of Pre-Existing Donor Specific Antibody and Amnestic Responses after Heart Transplantation

Sensitized patients have prolonged wait times for heart transplant and often low-level donor specific antibodies (DSA) will be crossed when accepting a donor heart. The purpose of this study was to determine if positive low-level DSA at the time of transplant increase in strength post transplant and increase the risk of antibody mediated rejection (AMR). We reviewed 72 heart transplant patients between 2010 and 2018 in whom low-level DSA were crossed. DSA strength, as measured by mean fluorescence intensity (MFI) and AMR on biopsy was assessed at 1, 3, 6, 12 months post transplant. Other outcomes assessed: freedom from first-year rejection (acute cellular rejection (ACR), any treated rejection (ATR)), freedom from cardiac allograft vasculopathy (CAV, as defined by stenosis ≥30% by angiography), and freedom from graft dysfunction (LVEF ≤40%). Patients were compared to a contemporaneous control group conditional to 1-year survival without DSA at transplant. Approximately one-third of patients with pre-existing DSA at transplant demonstrated an increase in DSA strength. Patients with pre-existing DSA had decreased freedom from ATR and AMR but no differences in freedom from CAV, graft dysfunction, or ACR compared to the control group. Crossing low-level DSA may increase the risk of AMR, but there is no difference in clinically important sequelae such as CAV or graft dysfunction. Thus, accepting low-level DSA at the time of transplant appears feasible and could broaden the donor pool.

Clinical Relevance of Posttransplant DSAs in Patients Receiving Desensitization for HLA-incompatible Kidney Transplantation.

Highly HLA-sensitized (HS) patients have an increased risk for the development of donor-specific antibodies (DSA) and antibody-mediated rejection (AMR) posttransplant. Here, we examined the risk for AMR in HS patients transplanted after desensitization (DES) who were DSA+ versus DSA- at transplant. We also examined the incidence and clinical impact of de novo DSAs (dnDSAs) and compared with dnDSA- patients. From January 2013 to October 2016, 90 HS patients (PRA > 80%, DSA+ = 50 versus DSA- = 40) received kidney transplantation after DES with IVIG + rituximab ± PLEX (plasma exchange) ± tocilizumab. DSAs were monitored at transplant and at 1, 3, 6, 12, 24, 36, and 48 months posttransplant. Patients were divided into 4 groups: DSA+/+ (n = 31), DSA+/- (n=19), DSA-/+ (n=10), and DSA-/- (n = 30). Median follow-up time was 2.9 years. DSA-negative patients who developed dnDSA had the highest incidence of AMR (70%) compared with the DSA+/+ (45%), DSA+/- (11%), and DSA-/- (10%) patients (P < 0.0001). Among patients who developed AMR, Banff 2013 AMR scores did not differ among the 4 groups. Graft survival and estimated glomerular filtration rate determinations at 4 years were similar. Persistence of preexisting DSAs or development of dnDSA after transplant is associated with an increased risk for AMR. Despite this, we did not observe a difference in Banff biopsy scores, graft survival, or patient survival compared with those without DSAs after transplant. Thus, for HS patients undergoing HLA-incompatible kidney transplant, DES therapy and frequent monitoring for dnDSAs appears critical for good long-term survival in at-risk groups.

The clinical impact of donor-specific antibodies on antibody-mediated rejection and long-term prognosis after heart transplantation.

Outcomes after cardiac transplantation have improved over past decades, but long-term graft survival remains limited in part because of uncertainty regarding clinical implications of donor-specific antibodies (DSAs). The purpose of this review is to consolidate recent advances in knowledge on the topic of DSA and their potential to impact long-term prognosis after heart transplantation. The presence of persistent DSA increases the risk of poor outcome after heart transplantation, including development of antibody-mediated rejection (AMR), graft failure, cardiac allograft vasculopathy, and mortality. Importantly, different DSA vary in clinical significance. DSA capable of activating the complement cascade portend a higher risk of developing AMR. human leukocyte antigen class I and class II antigens are expressed differently within the heart, and so, clinical manifestations of class I and class II DSA vary accordingly. Further, compared with class I, class II DSA carry an increased risk of graft loss and mortality. When comparing preexisting DSA with formation of de-novo DSA, de-novo DSA are associated with worse outcome. DSAs are generally associated worse long-term prognosis after heart transplantation but vary in their clinical significance. Recognition of specific risk profiles is essential for guiding posttransplant antibody management.

Strategy and clinical outcome of deceased donor kidney transplantation for presensitized recipients

Objective: To explore the management strategy and clinical outcome of renal transplantation in presensitized recipients using deceased donor kidneys. Methods: From January 2011 to June 2018, twenty-one presensitized patients, including 8 with positive donor specific antibodies (DSA) and 13 with positive panel-reactive antibodies (PRA) but no DSA, received renal retransplantation from deceased donors in our center. The incidence of delayed graft function (DGF) and acute rejection (AR), changes of DSA, and the graft and patient survival were retrospectively analyzed. Results: None of the renal allografts had primary non-function (PNF) and DGF after transplantation. Four of the 13 recipients with PRA(+)/DSA-had a total of 5 episodes of acute cell-mediated rejection (CMR), while 5 of 8 recipients with pre-existing DSA(+) developed AR, including 3 cases with CMR alone and 2 cases with mixed AR. All episodes of rejection were successfully reversed after targeted treatment. Interestingly, of the 8 recipients with positive preformed DSA, 4 cases with positive DR-DSA and/or class Ⅰ-DSA had their DSA disappeared after transplantation, whereas DQ-DSA remained positive in 4 of 5 recipients. After a median follow-up of 26 months, all recipients maintained normal renal allograft function, and the survival rates of both graft and recipient were 100%. Conclusions: With the use of deceased donors, kidney transplantation can be successfully performed in presensitized patients by appropriate HLA-matching screening, choosing donor kidneys with good quality, and the combination of optimal perioperative treatment.

Effect of recipient gender and donor-specific antibodies on antibody-mediated rejection after heart transplantation.

Gender-difference regarding antibody-mediated rejection (AMR) after heart transplantation has been described. However, no study accounted for the presence of preformed donor-specific antibodies (pfDSA), a known risk factor of AMR, more common among women than men. In a single-institution 6-year cohort (2010-2015), time to AMR was assessed, comparing men with women by survival analysis with a 1-year death-censored follow-up. All AMRs were biopsy proven. Confounding variables that were accounted for included mean intensity fluorescence (MFI) of pfDSA, recipient age, HLA-, size- and sex-mismatch. 463 patients were included. Overall incidence of AMR was 10.3% at 1year. After adjusting for confounding variables, independent risk factors of AMR were female recipient gender (adjusted hazard-ratio [adj. HR]=1.78 [1.06-2.99]), P=.03) and the presence of pfDSA (adj. HR=3.20 [1.80-5.70], P<.001). This association remained significant when considering pfDSA by their MFI; female recipient gender had an adj. HR=2.2 (P=.026) and MFI of pfDSA (per 1 MFI-increase) adj. HR=1.0002 (P<.0001). In this cohort, women were at higher risk of AMR than men and this risk increase was additive to that of pfDSA. These findings may suggest a gender-related difference in the severity of pfDSA.

P125 HLA allele specific antibodies: What should be entered in Unet, antigen, allele or epitope (case report)?

Aim Identification of donor-specific antibodies (DSA) represents one of the major functions of the HLA laboratory. Pre-existing DSAs are known to be important in organ allocation, while de novo developed DSA contribute to antibody (Ab) mediated rejection. Advances in solid-phase antibody analysis (SAA) now allow for the detection of HLA allele-specific Ab. The aim of this study was to examine HLA-A locus specific Ab in a kidney transplant candidate (TC). Methods A 64-yo male patient (typed A∗02:xx, 26:xx) was evaluated for a deceased donor kidney transplant. Two previous heart transplant (in 1986 and 2005) donors typed A1, A31 and A3, A31. HLA-A locus low and high resolution typing was performed using PCR-SSOP method (One Lambda Inc.), and sequence based typing (SBT) (GeneDX), respectively. Ab analysis was performed using SAA (One Lambda Inc.). Epitope analysis of HLA to which TC had Ab was conducted using HLAMatchmaker computer algorithm. Results Ab reactivity and antigen epitope analysis are presented in Table 1. Notably, TC had strongly reactive Ab against A∗26:01. Subsequent SBT of TC at A locus revealed presence of A∗02:01 and A∗26:09 alleles. The latter has a very low frequency in the US population. An epitope analysis of HLA-A locus Ab revealed that all positively-reactive HLA-A locus alleles share epitope 163R. Thus, we faced two questions. First, how should the TC’s typing at A locus be entered in Unet? Second, what antigens/alleles should be listed as unacceptable?. Conclusions The TC’s A locus typing was entered in Unet as A∗02:01/02:01 (considering changing A locus typing of the recipient to A2/A26 after kidney transplantation), and the list of unacceptable antigens included A1, A43, A25, A∗66:01, A∗11:01, A∗11:02, A26 (considering that all A26 donors will most likely have A∗26:01 allele). The results of this study present a new insight in organ allocation and post-transplant Ab monitoring, i.e. entering epitopes/eplets shared between unacceptable alleles (in this case 163R) instead of unacceptable UNOS antigens.