ABO-incompatible Transplantation Research Articles

ABO Incompatible Kidney Transplant in a Patient With Atypical Hemolytic Uremic Syndrome: Case Report

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection. Graft acceptance was facilitated by triple immunosuppression (steroid, tacrolimus, and mycophenolate mofetil), and 4-month serum creatinine follow-up indicated the absence of antibody-mediated rejection and recurrence of aHUS. This case demonstrates that in patients with aHUS, ABOi renal transplant can be performed successfully.

Impact of B Cell Depletion on COVID-19 in Kidney Transplant Recipients

Kidney transplant recipients are patients at high risk for coronavirus disease 2019 (COVID-19) due to being on immunosuppressive therapy. B cell depletion therapy, including rituximab, is an important strategy for ABO-incompatible transplants. However, knowledge about the effect of B cell depletion therapy on COVID-19 is lacking. Thirty kidney transplant recipients who developed COVID-19 were included in this study. To examine the impact of B cell depletion therapy, we retrospectively investigated the relationship between the background of the patients and the clinical outcome. Of the 30 patients, 13 received B cell depletion therapy. The median time between transplant and onset of COVID-19 was 6.1 years after transplantation; however, nine cases remained markedly depleted of CD19(+) cells (<4.0%). The patients were assigned to the normal (n = 21) and depletion groups (n = 9). Progression rates in the depletion and normal groups were 55.6% and 9.5%, respectively (p = 0.014). Furthermore, the survival rate was significantly lower in the depletion group (100% in the normal group vs. 66.7% in the depletion group; p = 0.021). B cell depletion therapy may have long-term effects and increase the risk of COVID-19 in kidney transplant recipients.

#3962 BALANCING THE RISK OF ALLOIMMUNITY WHILE MINIMIZING IMMUNOSUPPRESSIVE THERAPY: A RETROSPECTIVE STUDY OF PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Kidney transplantation is the best treatment for end-stage kidney disease, but life with a kidney allograft comes with significant challenges. Many paediatric kidney transplant recipients (KTRs) experience side effects from immunosuppressive medication. Reducing the medication is often necessary, but the reduction comes with a risk of inducing alloimmunity. We aimed to describe the alteration in immunosuppressive medication after kidney transplantation, the reasons for the reductions, and the possible impact on alloimmunity. Method 49 paediatric KTRs aged 1-16 years, receiving a kidney allograft from 2009 to 2020 in a Danish single centre were retrospectively studied. The standard protocol for immunologically low risk KTRs was steroid-free immunosuppression with basiliximab as induction, tacrolimus and mycophenolate mofetil (MMF) as maintenance therapy. KTRs were screened for anti-HLA antibodies with mixed and single bead antigen kits. We defined reduced immunosuppression as a KTR receiving one; OR two immunosuppressive medications AND MMF below 600 mg/m2. Results 49 KTRs received a kidney allograft, two were ABO incompatible transplantations and six KTRs had pretransplant donor specific antibodies. The median age of the KTRs was 11 years (IQR 8), with a median follow-up time of 5 years (IQR 5). In total, 78% KTRs received standard immunosuppressive therapy (steroid free). 5-year death censored (one KTR died) graft survival was 88%, and the cumulative incidence of rejection was 4% (95% CI: -1.5; 5.5) within the first year. None of the six graft losses were related to alloimmunity. 11.4% developed de novo donor specific antibodies (dnDSA) within a median of 3.91 years (IQR 2.28; range: 2.22-9.20) from transplantation. At transplantation, 6% received reduced immunosuppressive medication increasing to 74% at year one. Immunosuppression (primarily MMF) remained reduced in most of the KTRs during follow-up (Figure 1). Side effects predominantly to MMF led to the reduction. Leukopenia caused a reduction in 77%, gastrointestinal side effects in 34%, EBV in 19% (two KTRs developed PTLD), CMV in 15%, and BK polyomavirus in 15%. The reduction was significantly more pronounced in KTRs under 11 years (87% vs. 61%, p-0.044). Tacrolimus seemed well tolerated and was sufficiently regulated according to a target through of five microg/L two months after transplantation (Figure 2). Conclusion Despite 74% of the KTRs receiving reduced immunosuppressive medication according to our protocol, the rejection rate was low, the graft survival was comparable to European reports, and only 11% developed dnDSA during follow-up. Scheduled reduction of MMF shortly after transplantation could decrease the adverse side effects and improve the treatment of paediatric KTRs.

#6880 PREDICTION OF GRAFT SURVIVAL PRIOR TO ACCEPTING AN OFFER FOR LIVING DONOR KIDNEY TRANSPLANT: AN ARTIFICIAL INTELLIGENCE APPROACH

Abstract Background and Aims The current available models for evaluation of outcomes of living donor kidney transplant before accepting an offer are poorly developed, reported, validated and have small sample sizes. We aim to use Artificial Intelligence to build a model that can accurately predict death censored graft survival for living donor kidney transplant prior to accepting an offer. Method All living kidney transplant patients who were: registered in the UNOS database between 1/1/2007 and 1/6/2021, maintained on TAC/MMF immunotherapy were included in our analysis. We excluded patients with age<18 years old and ABO incompatible transplant. We divided the data randomly into training and testing dataset with ratio 80:20. We performed recursive feature elimination to select the important ones for prediction. Features were selected based on their Gini impurity scores. We performed Artificial Neural Network analysis (ANN). We evaluated the model using Harrell Concordance-time-dependent score (for discrimination), and Integrated Brier score (for calibration). We also assessed dynamic AUC for model performance. Results 54,110 living donor kidney transplant patients were included in the study. Harrell C-Statistic scores were 0.70 at 5 years post-transplant, 0.68 at 10 years post-transplant and 0.68 at 13 years post-transplant, indicating very high discrimination power. Integrated Brier Score was 0.08, indicating very high calibration score for our model. Dynamic AUC scores were 0.71 at 5 years post-transplant and 0.68 at 10- and 13-years post-transplant, indicating adequate performance for our model. The key players in our model were recipient age (variable importance = 0.26), donor age (variable importance = 0.17), donor ethnicity (variable importance = 0.90), followed by dialysis vintage pre-transplantation. Conclusion The ANN model had high discrimination, calibration, and performance indices for predicting death censored graft survival prior to transplant. It can aid the clinical decision for management of the transplant patients. We are currently developing a user-friendly web application that can be used to apply the ANN model for prediction. Our model can help ranking potential living kidney donors based on graft outcomes. Therefore, our model can help improve current outcomes of kidney paired exchange schemes.

Impact of the Pediatric ABO Policy Change on Listings, Transplants, and Outcomes for Children Younger Than 2 Years Listed for Heart Transplantation in the United States

We assessed the impact of the liberalized ABO pediatric policy change on candidate characteristics and outcomes for children undergoing heart transplant (HT). Children <2 years undergoing HT with ABO strategy reported at listing and HT from December 2011 to November 2020 to the Scientific Registry of Transplant Recipients database were included. Characteristics at listing, HT, and outcomes during the waitlist and post-transplant were compared before the policy change (December 16, 2011 to July 6, 2016), and after the policy change (July 7, 2016 to November 30, 2020). The percentage of ABO-incompatible (ABOi) listings did not increase immediately after the policy change (P = .93); however, ABOi transplants increased by 18% (P < .0001). At listing, both before and after the policy change, ABOi candidates had higher urgency status, renal dysfunction, lower albumin, and required more cardiac support (intravenous inotropes, mechanical ventilation) than those listed ABO compatible (ABOc). On multivariable analysis, there were no differences in waitlist mortality between children listed as ABOi and ABOc before the policy change (adjusted hazard ratio [aHR] 0.80, 95% confidence interval [CI] 0.61-1.05, P = .10) or after the policy change (aHR 1.2, 95% CI 0.85-1.6, P = .33). Post-transplant graft survival was worse for ABOi transplanted children before the policy change (aHR 1.8, 95% CI 1.1-2.8, P = .014), but not significantly different after the policy change (aHR 0.94, 95% CI 0.61-1.4, P = .76). After the policy change, ABOi listed children had significantly shorter waitlist times (P < .05). The recent pediatric ABO policy change has significantly increased the percentage of ABOi transplantations and decreased waitlist times for children listed ABOi. This change in policy has resulted in broader applicability and actual performance of ABOi transplantation with equal access to ABOi or ABOc organs, and thus eliminated the potential disadvantage of only secondary allocation to ABOi recipients.

Sex, T Cells, and the Microbiome in Natural ABO Antibody Production in Mice.

"Natural" ABO antibodies (Abs) are produced without known exposure to A/B carbohydrate antigens, posing significant risks for hyperacute rejection during ABO-incompatible transplantation. We investigated anti-A "natural" ABO antibodies versus intentionally induced Abs with regard to the need for T-cell help, the impact of sex, and stimulation by the microbiome. Anti-A was measured by hemagglutination assay of sera from untreated C57BL/6 wild-type (WT) or T cell-deficient mice of both sexes. Human ABO-A reagent blood cell membranes were injected intraperitoneally to induce anti-A Abs. The gut microbiome was eliminated by maintenance of mice in germ-free housing. Compared with WT mice, CD4 + T-cell knockout (KO), major histocompability complex-II KO, and αβ/γδ T-cell receptor KO mice produced much higher levels of anti-A nAbs; females produced dramatically more anti-A nAbs than males, rising substantially with puberty. Sensitization with human ABO-A reagent blood cell membranes did not induce additional anti-A in KO mice, unlike WT. Sex-matched CD4 + T-cell transfer significantly suppressed anti-A nAbs in KO mice and rendered mice responsive to A-sensitization. Even under germ-free conditions, WT mice of several strains produced anti-A nAbs, with significantly higher anti-A nAbs levels in females than males. Anti-A nAbs were produced without T-cell help, without microbiome stimulation, in a sex- and age-dependent manner, suggestive of a role for sex hormones in regulating anti-A nAbs. Although CD4 + T cells were not required for anti-A nAbs, our findings indicate that T cells regulate anti-A nAb production. In contrast to anti-A nAbs, induced anti-A production was T-cell dependent without a sex bias.

ABO-Incompatible Renal Transplant: A Single-Center Experience from India.

In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.

TSR: A User-Friendly R Shiny Application for Assessment of Optimal Blood Product Selection in ABO-Incompatible Hematopoietic Stem Cell Transplantation.

Patients undergoing hematopoietic stem cell transplant (HSCT) need frequent transfusions, until their red blood cells (RBCs) and platelets start to recover. The safe transfusion for patients who receive ABO-incompatible HSCT is essential to the transplant process. To date, there is no user-friendly tool to choose the right blood product for transfusion treatment, despite the number of guidelines and expert advice on the subject. R/shiny is a powerful programming language for clinical data analysis and visualization. It can create interactive web applications that work in real-time. The web application named TSR was built using R programming, simplifying blood transfusion practice for ABO-incompatible HSCT with a one-click solution. The TSR is divided into four main tabs. The home tab provides an overview of the application, while RBC, plasma and platelet transfusion tabs offer tailored suggestions for blood product selection in each category. Unlike traditional methods that rely on treatment guidelines and specialist consensus, TSR leverages the power of the R/Shiny interface to extract critical content based on user-specified parameters, providing an innovative approach to improve transfusion support. The present study highlights that the TSR enables real-time analysis, and promotes transfusion practice by offering a unique and efficient one-key output for blood product selection to ABO-incompatible HSCT. TSR has the potential to become a widely-utilized tool for transfusion services, providing a reliable and user-friendly solution that enhances transfusion safety in clinical practice.

THU-513 - Pre-transplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation

THU-513 - Pre-transplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation

Outcomes after ABO incompatible pediatric liver transplantation are comparable to ABO identical/compatible transplant.

ABO incompatible (ABOi) liver transplantation (LT) was initially associated with a higher incidence of vascular, biliary, and rejection complications and a lower survival than ABO compatible (ABOc) LT. Various protocols have been proposed to manage anti-isohemagglutinin antibodies and hyperacute rejection. We present our experience with a simplified protocol using only plasmapheresis. A retrospective review of all patients who received an ABOi LT at ourinstitution was performed. Comparisons were made based on era (early: 1997-2008, modern: 2009-2020) and severity of disease (status 1 vs. exception PELD at transplant). A pair-matched comparison was done to patients who received an ABOc LT. p < 0.05 was considered significant. 17 patients received 18 ABOi LT (3 retransplants). Median age at transplant was 7.4 months (1.1-28.9). 66.7% patients were listed as status 1. Hepatic artery thrombosis (HAT) occurred in one patient (5.6%), there were 2 cases of portal vein thrombosis (PVT) (11.1%), and 2 biliary strictures (11.1%). Patient and graft survival improved in the ABOi modern era, although not significantly. In the pair-matched comparison, complications (HAT p = 0.29; PVT p = 0.37; biliary complications p = 0.15) and survival rates were similar. Patient and graft survivals were 100% in the non-status 1 ABOi patients compared to 67% (p = 0.11) and 58% (p = 0.081) respectively for patients who were transplanted as status 1. ABO incompatible liver transplants in infants with a high PELD score have excellent outcomes. Indications for ABO incompatible transplants should be liberalized to prevent deaths on the waiting list or deterioration of children with high PELD scores.

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

Simultaneous 3-way Paired Exchange Liver Transplantation Without Nondirected Donation: Novel Strategy to Expand the Donor Pool.

Large volume plasmapheresis using a single-use immunoadsorption column: A cost-effective approach for desensitization in ABO-incompatible liver transplant.

Liver transplant is a life-saving treatment, but due to the limited availability of suitable liver donors, ABO-incompatible liver transplants (ABOi-LT) are conducted to increase the availability of liver donors. Perioperative desensitization for ABOi-LT is an established strategy to circumvent the risk of graft rejection. A single prolonged session can be performed to achieve the desired titers to avoid using multiple immunoadsorption (IA) columns or off-label reuse of single-use columns. This study retrospectively assessed the effectiveness of a single prolonged plasmapheresis session using IA as a desensitization strategy in live donor liver transplant (LDLT). This retrospective observational study conducted at a center for liver diseases in North India on six ABOi-LDLT patients who underwent single prolonged IA sessions in the perioperative period from January 2018 to June 2021. Median baseline titer in patients was 320 (64, 1024). The median plasma volume adsorbed was 7.5 volumes (4, 8) per procedure, with a mean procedure time of 600 min (310-753). The reduction in titer ranged from 4 log to 7 log reduction per procedure. Two patients developed transient hypotension during the procedure, which was managed successfully. The median duration of pre-transplant hospital stay was 1.5 days (1, 3). Desensitization therapy helps overcome the ABO barrier and decreases the waiting period before a transplant when ABO identical donors are unavailable. A single prolonged IA session reduces the cost of additional IA columns and hospital stay, thus making it a cost-effective approach to desensitization.

Significance of C4d expression in peritubular capillaries concurrent with microvascular inflammation in for-cause biopsies of ABO-incompatible renal allografts.

Pathologic diagnosis of antibody-mediated rejection (ABMR) in ABO-incompatible (ABOi) transplantation patients is often challenging because patients without ABMR are frequently immunopositive for C4d. The aim of this study was to determine whether C4d positivity with microvascular inflammation (MVI), in the absence of any detectable donor-specific antibodies (DSAs) in ABOi patients, could be considered as ABMR. A retrospective study of 214 for-cause biopsies from 126 ABOi kidney transplantation patients was performed. Patients with MVI score of ≥2 and glomerulitis score of ≥1 (n = 62) were divided into three groups: the absolute ABMR group (DSA-positive, C4d-positive or C4d-negative; n = 36), the C4d-positive group (DSA-negative, C4d-positive; n = 22), and the C4d-negative group (DSA-negative, C4d-negative; n = 4). The Banff scores, estimated glomerular filtration rates (eGFRs), and graft failure rates were compared among groups. C4d-positive biopsies showed higher glomerulitis, peritubular capillaritis, and MVI scores compared with C4d-negative specimens. The C4d-positive group did not show significant differences in eGFRs and graft survival compared with the absolute ABMR group. The results indicate that C4d positivity, MVI score of ≥2, and glomerulitis score of ≥1 in ABOi allograft biopsies may be categorized and treated as ABMR cases.

Outcome of ABO-Incompatible Living Donor Kidney Transplantation: A Single Center Observational Study from Nepal

Introduction: Kidney transplantation is the most effective treatment for end-stage renal disease (ESRD) patients. However, the increasing number of ESRD patients and the limited availability of living and cadaveric donors has led to a growing waiting list for kidney transplantation. ABO-incompatible transplantation has emerged as an alternative for these patients in Nepal. Methods: This was an observational study of all the patients who underwent kidney transplantation from March 2017-Feb 2019. Data on demography of recipients and donor, blood group, human leukocyte antigen mismatch, induction agent, post-operative complications and creatinine clearance at discharge and one-year post-transplant were collected and analysed. Then we compared patient and kidney graft survival at one year between ABO incompatible and ABO compatible recipients. Results: During the study period, there were total of 124 kidney transplant recipients among them 12 were ABO incompatible and 112 were ABO compatible recipients. The study showed slightly lower patient and graft survival in ABO-incompatible recipients than ABO compatible recipients (83.3% vs 99.2%, p&lt;0.001). However, death-censored graft survival were similar in both groups (100%,p&lt;0.001). The graft function at one year measured by creatinine clearance was better in ABO-incompatible recipients than ABO-compatible recipients (67.1±11.75 vs 61.87±12.82, p&lt;0.001). Postoperative complications were slightly higher, however, complications at one year were lower in ABO-incompatible recipients. Conclusion: The study showed that living donor ABO-incompatible kidney transplant recipients have a good outcome at one year but is associated with greater risks of patient and graft loss at early transplant period compared to ABO-compatible recipients.

An Analysis of 186 Transplants for Pediatric or Congenital Heart Disease: Impact of Pretransplant VAD

BackgroundWe reviewed our management strategy and outcome data for all 181 patients with pediatric or congenital heart disease who received 186 heart transplants from January 1, 2011, to March 1, 2022, and evaluated the impact of pretransplant ventricular assist device (VAD). MethodsContinuous variables are presented as mean (SD); median [interquartile range] (range). Categorical variables are presented as number (percentage). Univariable associations with long-term mortality were assessed with Cox proportional hazards models. Impact of pretransplant VAD on survival was estimated with multivariable models. ResultsPretransplant VAD was present in 53 of 186 transplants (28.5%). Patients with VAD were younger (years): 4.8 (5.6); 1 [0.5-8] (0.1-18) vs 12.1 (12.7); 10 [0.7-17] (0.1-58); P = .0001. Patients with VAD had a higher number of prior cardiac operations: 3.0 (2.3); 2 [1-4] (1-12) vs 1.8 (1.9); 2 [0-3] (0-8); P = .0003. Patients with VAD were also more likely to receive an ABO-incompatible transplant: 10 of 53 (18.9%) vs 9 of 133 (6.8%); P = .028.Univariable associations with long-term mortality included:•Prior cardiac operation: hazard ratio (HR), 6.0 (1.41-25.4); P = .015•Number of prior cardiac operations: HR multiplies by 1.3 for each additional operation (1.12-1.50); P = .0004•Functionally univentricular heart: HR, 2.4 (1.05-5.49); P = .038•Congenital heart disease (vs acquired): HR, 5.7 (1.69-18.9); P = .005•Pretransplant renal dysfunction: HR, 3.4 (1.54-7.48); P = .003In multivariable analysis, pretransplant VAD did not impact survival while controlling for each one of the factors shown in univariable analysis to be associated with long-term mortality. Kaplan-Meier 5-year survival (95% CI) was 85.8% (80.0%-92.1%) for all patients, 84.3% (77.2%-92.0%) without pretransplant VAD, and 91.1% (83.1%-99.9%) with pretransplant VAD. ConclusionsOur single-institution analysis of 181 patients receiving 186 heart transplants for pediatric or congenital heart disease over 11.25 years reveals similar survival in patients with (n = 51) and without (n = 130) pretransplant VAD. The presence of a pretransplant VAD is not a risk factor for mortality after transplantation for pediatric or congenital heart disease.

Zero Mortality in Living-Donor Liver Transplantation for Primary Biliary Cholangitis in Patients With a Meld Score of

Although primary biliary cholangitis (PBC) is considered a good indication for living-donor liver transplantation (LDLT), the postoperative results are not well known. At Jikei University Hospital, 14 patients with PBC underwent LDLT from February 2007 to June 2022. We consider PBC with a Model for End-Stage Liver Disease (MELD) score of <20 to indicate LDLT. We performed a retrospective analysis of the patients' clinical records. The patients' median age was 53 years, and 12 of the 14 patients were female. A right graft was used in 5 patients, and 3 ABO-incompatible transplants were performed. The living donors were children in 6 cases, partners in 4 cases, and siblings in 4 cases. The preoperative MELD scores ranged from 11 to 19 (median, 15). The graft-to-recipient weight ratio ranged from 0.8 to 1.1 (median, 1.0). The median operative time for donors and recipients was 481 and 712 minutes, respectively. The median operative blood loss of donors and recipients was 173 and 1,800 mL, respectively. The median postoperative hospital stay of donors and recipients was 10 and 28 days, respectively. All recipients recovered satisfactorily and remained well during a median follow-up of 7.3 years. Three patients underwent a liver biopsy after LDLT because of acute cellular rejection without histologic findings of PBC recurrence. Living-donor liver transplantation provides satisfactory long-term survival for patients with PBC with a graft-to-recipient weight ratio of >0.7 and MELD score of <20 without hepatocellular damage and only portal vein hypertension.

(731) Enzymatic Removal of A-Antigen in a Mouse Model of ABO-Incompatible (ABOi) Transplantation

(731) Enzymatic Removal of A-Antigen in a Mouse Model of ABO-Incompatible (ABOi) Transplantation

Outcomes of ABO Incompatible Kidney Transplantation:A Single Center Experience

Background: Kidney transplantation (KT) is the treatment of choice for patients with end-stage renal disease (ESRD). General organ donor shortage remains an important limitation on KT, given the increasing number of patients waiting for transplantation. This has led to the adoption of different strategies to increase the pool of donors, such as ABO incompatible (ABOi) living KT. In this single center study, we retrospectively evaluated all donor/recipient pairs proposed for ABOi KT since the beginning of this transplantation program in our hospital in 2014. Methods: Between November 2014 and March 2022, 609 deceased donor and 223 living donor KT were performed in our center. Seventy-one donor/recipient pairs were proposed for ABOi KT and were evaluated for ABO/Rh group, Coombs tests, human leukocyte antigen (HLA) type I (A, B, C) and II (DR) high resolution genotyping and receptor to donor isoagglutinin titers and HLA antibodies. Recipients with immunoglobulins G (IgG) and/or M (IgM) isoagglutinin titers &gt; 1:512 and/or with HLA donor specific alloantibodies (DSAs) were excluded from the ABOi transplantation program. Isoagglutinins removal was performed recurring to therapeutic plasma exchange (TPE) and/or immunoadsorption techniques. Transplanted patients were evaluated for demographic data, diagnosis, relationship with donor, sessions of antibodies removal, pre- and post-KT isoagglutinin titers, graft function, transfusion support, significant complications and overall patient survival. Results: Eighteen patients (14 males and 4 females) were transplanted with an ABOi graft out of 71 ABOi studied pairs. Median baseline IgG and IgM isoagglutinin titers were 1:32 (min 1:2, max 1:256) and 1:8 (min 1:2, max 1:32), respectively. Fifteen patients (83.3%) had pre-KT TPE and/or immunoadsorption sessions for isoagglutinin removal (mean 2.4 ± 1.8 session per patient). Seven patients (36.8%) were submitted to post-KT TPE (mean 1.9 ± 3.2 session per patient). No acute antibody mediated rejection was observed and overall graft survival was 100% on a follow-up period between 3 and 92 months (47.6 ± 25.2 months). All patients were dialysis-free with serum creatinine steady levels (median 1.4 mg/dL) at 47.6 ± 25.2 months of follow up. Conclusion: These results confirm that ABOi KT is a viable treatment for patients with ESRD, thus expanding living donor pool and reducing access time to transplantation.

Evaluating the Potential for ABO-incompatible Islet Transplantation: Expression of ABH Antigens on Human Pancreata, Isolated Islets, and Embryonic Stem Cell-derived Islets.

ABO-incompatible transplantation has improved accessibility of kidney, heart, and liver transplantation. Pancreatic islet transplantation continues to be ABO-matched, yet ABH antigen expression within isolated human islets or novel human embryonic stem cell (hESC)-derived islets remain uncharacterized. We evaluated ABH glycans within human pancreata, isolated islets, hESC-derived pancreatic progenitors, and the ensuing in vivo mature islets following kidney subcapsular transplantation in rats. Analyses include fluorescence immunohistochemistry and single-cell analysis using flow cytometry. Within the pancreas, endocrine and ductal cells do not express ABH antigens. Conversely, pancreatic acinar tissues strongly express these antigens. Acinar tissues are present in a substantial portion of cells within islet preparations obtained for clinical transplantation. The hESC-derived pancreatic progenitors and their ensuing in vivo-matured islet-like clusters do not express ABH antigens. Clinical pancreatic islet transplantation should remain ABO-matched because of contaminant acinar tissue within islet preparations that express ABH glycans. Alternatively, hESC-derived pancreatic progenitors and the resulting in vivo-matured hESC-derived islets do not express ABH antigens. These findings introduce the potential for ABO-incompatible cell replacement treatment and offer evidence to support scalability of hESC-derived cell therapies in type 1 diabetes.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

Human immunodeficiency virus (HIV)-positive patients coinfected with hepatitis B virus (HBV) are eligible for liver transplantation (LT) in Africa and Southeast Asia, particularly China. However, the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT (ABOi-LT) is unknown. To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with end-stage liver disease (ESLD). We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT. The pretransplantation HIV viral load was undetectable, with no active opportunistic infections. Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses, followed by an intraoperative regimen of intravenous immunoglobulin, methylprednisolone, and basiliximab. Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil, and prednisone. At the intermediate-term follow-up, patients showed undetectable HIV viral load, CD4(+) T cell counts greater than 150 cells/μL, no HBV recurrence, and stable liver function. A liver allograft biopsy showed no evidence of acute cellular rejection. Both patients survived at 36-42 mo of follow-up. This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes, suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.