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Characterization of ABH-subtype donor-specific antibodies in ABO-A-incompatible kidney transplantation.

ABSTRACT: ABO-incompatible (ABOi) transplantation requires preemptive antibody reduction; however, the relationship between antibody-mediated rejection (AMR) and ABO-antibodies, quantified by hemagglutination (HA), is inconsistent, possibly reflecting variable graft resistance to AMR or HA assay limitations. Using an ABH-glycan microarray, we quantified ABO-A antigen-subtype (A-subtype)-specific IgM and IgG in 53 ABO-O recipients of ABO-A kidneys, before and after antibody removal (therapeutic plasma exchange [TPE] or ABO-A-trisaccharide immunoadsorption [IA]) and 1-year posttransplant. IgM binding to all A-subtypes correlated highly (R² ≥ .90) and A-subtype antibody specificities was reduced equally by IA versus TPE. IgG binding to the A-subtypes (II-IV) expressed in kidney correlated poorly (.27 ≤ R² ≤ .69). Reduction of IgG specific to A-subtype-II was equivalent for IA and TPE, whereas IgG specific to A-subtypes-III/IV was not as greatly reduced by IA (p < .005). One-year posttransplant, IgG specific to A-II remained the most reduced antibody. Immunostaining revealed only A-II on vascular endothelium but A-subtypes II-III/IV on tubular epithelium. These results show that ABO-A-trisaccharide is sufficient for IgM binding to all A-subtypes; this is true for IgG binding to A-II, but not subtypes-III/IV, which exhibits varying degrees of specificity. We identify A-II as the major, but importantly not the sole, antigen relevant to treatment and immune modulation in adult ABO-A-incompatible kidney transplantation.

SUBMITTER: Bentall A

PROVIDER: S-EPMC8597088 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Effect of Donor and Recipient ABH-Secretor Status on ABO-Incompatible Living Donor Kidney Transplantation.

Project description:IntroductionABO blood group antigens within grafts are continuously exposed to anti-A/B antibodies in the serum of recipients after ABO-incompatible (ABOi) kidney transplantation and are instrumental in antibody-mediated rejection. Some individuals secrete soluble blood group antigens into body fluids. In this study, we investigated the effect of donor and recipient secretor status on the outcomes of ABOi kidney transplantation.MethodsData of a total of 32 patients with ABOi living donor kidney transplantation were retrospectively collected between 2014 and 2020 in West China Hospital. The genotype and phenotype of both donors and recipients were examined and evaluated with post-transplantation anti-A/B titer changes, graft function, and rejection.ResultsOf the 32 recipients and 32 donors, 23 (71.9%) recipients and 27 (84.4%) donors had secretor genotypes, whereas 9 (28.1%) recipients and 5 (15.6%) donors did not. Anti-A/B titers after ABOi kidney transplantation were not significantly influenced by the secretor status of either donors or recipients. The post-transplantation serum creatinine (Scr) levels and estimated glomerular filtration rate (eGFR) was better in weak- or non-secretor recipients at day 30 (Scr P = 0.047, eGFR P = 0.008), day 90 (Scr P = 0.010, eGFR P = 0.005), and month 9 (eGFR P = 0.008), and recipients from secretor donors had a lower incidence of graft rejection in the first year after ABOi transplantation (P = 0.004).ConclusionsA weak secretor status phenotype was found in both genotypes, i.e., individuals who secreted soluble antigens as well as those who did not. The recipient ABH-secretor status may have an influence on early posttransplant renal function, and the donor ABH-secretor status might affect the incidence of graft rejection.

| S-EPMC8236826 | biostudies-literature

Impact of ABO incompatible kidney transplantation on living donor transplantation.

Project description:BackgroundABO incompatible kidney transplantation (ABOi-KT) is an important approach for overcoming donor shortages. We evaluated the effect of ABOi-KT on living donor KT.MethodsTwo nationwide transplantation databases were used. We evaluated the impact of ABOi-KT on overall living donor transplant activity and spousal donation as subgroup analysis. In addition, we compared the clinical outcome between ABOi-KT and ABO compatible KT (ABOc-KT) from spousal donor, and performed a Cox proportional hazards regression analysis to define the risk factors affecting the allograft outcomes.ResultThe introduction of ABOi-KT increased overall living donor KT by 12.2% and its portion was increased from 0.3% to 21.7% during study period. The ABOi-KT in living unrelated KT was two times higher than that of living related donor KT (17.8 vs.9.8%). Spousal donor was a major portion of living unrelated KT (77.6%) and ABOi-KT increased spousal donation from 10% to 31.5% in living donor KT. In addition, increasing rate ABOi-KT from spousal donor was 10 times higher than that of living related donor. The clinical outcome (incidence of acute rejection, allograft function, and allograft and patient survival rates) of ABOi-KT from spousal donor was comparable to that of ABOc-KT. Neither ABO incompatibility nor spousal donor was associated with acute rejection or allograft failure on multivariate analysis.ConclusionsABOi-KT increased overall living donor KT, and ABOi-KT from spousal donor is rapidly increasing with favorable clinical outcomes.

| S-EPMC5360260 | biostudies-literature

ABO-Incompatible Kidney Transplantation.

Project description:ABO-incompatible (ABOi) kidney transplantation has long been considered a contraindication to successful kidney transplantation. During the last 25 years, increasing organ shortage enforced the development of strategies to overcome the ABO antibody barrier. In the meantime, ABOi kidney transplantation has become a routine procedure with death-censored graft survival rates comparable to the rates in compatible transplantations. Desensitization is usually achieved by apheresis and B cell-depleting therapies that are accompanied by powerful immunosuppression. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABOi kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation, but is poorly understood. There is still concern, however, that infectious complications such as viral disease, Pneumocystis jirovecii pneumonia, and severe urinary tract infections are increased after ABOi transplantations. Recent data from the Collaborative Transplant Study show that during the first year after kidney transplantation, one additional patient death from an infectious complication occurs in 100 ABOi kidney transplant recipients. Herein, we review the recent evidence on ABOi kidney transplantation with a focus on desensitization strategies and respective outcomes.

| S-EPMC5338156 | biostudies-literature

ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis.

Project description:Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO-incompatible (ABOi) kidney transplantation with matched ABO-compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death-censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity-matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49-0.96)] and non-significantly different from ABOc living donor recipients [HR 1.28 (0.90-1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72-4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab-treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl].

| S-EPMC9299000 | biostudies-literature

Perioperative ABO Blood Group Isoagglutinin Titer and the Risk of Acute Kidney Injury after ABO-Incompatible Living Donor Liver Transplantation.

Project description:For ABO-incompatible liver transplantation (ABO-i LT), therapeutic plasma exchange (TPE) is performed preoperatively to reduce the isoagglutinin titer of anti-ABO blood type antibodies. We evaluated whether perioperative high isoagglutinin titer is associated with postoperative risk of acute kidney injury (AKI). In 130 cases of ABO-i LT, we collected immunoglobulin (Ig) G and Ig M isoagglutinin titers of baseline, pre-LT, and postoperative peak values. These values were compared between the patients with and without postoperative AKI. Multivariable logistic regression analysis was used to evaluate the association between perioperative isoagglutinin titers and postoperative AKI. Clinical and graft-related outcomes were compared between high and low baseline and postoperative peak isoagglutinin groups. The incidence of AKI was 42.3%. Preoperative baseline and postoperative peak isoagglutinin titers of both Ig M and Ig G were significantly higher in the patients with AKI than those without AKI. Multivariable logistic regression analysis showed that preoperative baseline and postoperative peak Ig M isoagglutinin titers were significantly associated with the risk of AKI (baseline: odds ratio 1.06, 95% confidence interval 1.02 to 1.09; postoperative peak: odds ratio 1.08, 95% confidence interval 1.04 to 1.13). Cubic spline function curves show a positive relationship between the baseline and postoperative peak isoagglutinin titers and the risk of AKI. Clinical outcomes other than AKI were not significantly different according to the baseline and postoperative peak isoagglutinin titers. Preoperative high initial and postoperative peak Ig M isoagglutinin titers were significantly associated with the development of AKI. As the causal relationship between high isoagglutinin titers and risk of AKI is unclear, the high baseline and postoperative isoagglutinin titers could be used simply as a warning sign for the risk of AKI after liver transplantation.

| S-EPMC8070732 | biostudies-literature

Economic Impacts of ABO-Incompatible Live Donor Kidney Transplantation: A National Study of Medicare-Insured Recipients.

Project description:The infrequent use of ABO-incompatible (ABOi) kidney transplantation in the United States may reflect concern about the costs of necessary preconditioning and posttransplant care. Medicare data for 26 500 live donor kidney transplant recipients (2000 to March 2011), including 271 ABOi and 62 A2-incompatible (A2i) recipients, were analyzed to assess the impact of pretransplant, transplant episode and 3-year posttransplant costs. The marginal costs of ABOi and A2i versus ABO-compatible (ABOc) transplants were quantified by multivariate linear regression including adjustment for recipient, donor and transplant factors. Compared with ABOc transplantation, patient survival (93.2% vs. 88.15%, p = 0.0009) and death-censored graft survival (85.4% vs. 76.1%, p < 0.05) at 3 years were lower after ABOi transplant. The average overall cost of the transplant episode was significantly higher for ABOi ($65 080) compared with A2i ($36 752) and ABOc ($32 039) transplantation (p < 0.001), excluding organ acquisition. ABOi transplant was associated with high adjusted posttransplant spending (marginal costs compared to ABOc - year 1: $25 044; year 2: $10 496; year 3: $7307; p < 0.01). ABOi transplantation provides a clinically effective method to expand access to transplantation. Although more expensive, the modest increases in total spending are easily justified by avoiding long-term dialysis and its associated morbidity and cost.

| S-EPMC4844838 | biostudies-literature

Long-term Outcomes of ABO-incompatible Pediatric Living Donor Liver Transplantation.

Project description:BACKGROUND:ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been performed to compensate for donor shortage. To date, few studies have reported detailed B-cell desensitization protocols and long-term outcomes of ABOi pediatric LDLT. METHODS:Twenty-nine pediatric ABOi LDLT recipients were retrospectively analyzed. We compared the clinical outcomes between ABOi (n = 29) and non-ABOi (n = 131) pediatric LDLT recipients. Furthermore, we evaluated the safety and efficacy of our rituximab-based regimen for ABOi pediatric LDLT (2 ? age < 18; n = 10). RESULTS:There were no significant differences in the incidence of infection, vascular complications, biliary complications, and acute cellular rejection between ABOi and non-ABOi groups. The cumulative graft survival rate at 1, 3, and 5 years for non-ABOi group were 92.1%, 87.0%, and 86.1%, and those for ABOi group were 82.8%, 82.8%, and 78.2%, respectively. Rituximab-based desensitization protocol could be performed safely, and reduced CD19+ lymphocyte counts effectively. Although rituximab-treated ABOi group showed comparable clinical outcomes and graft survival rate, 2 patients developed antibody-mediated rejection. CONCLUSIONS:ABOi LDLT is a feasible option for pediatric end-stage liver disease patients. However, it should be noted that current desensitization protocol does not completely prevent the onset of antibody-mediated rejection in several cases.

| S-EPMC6166697 | biostudies-literature

Early clinical complications after ABO-incompatible live-donor kidney transplantation: a national study of Medicare-insured recipients.

Project description:Descriptions of the sequelae of ABO-incompatible (ABOi) kidney transplantation are limited to single-center reports, which may lack power to detect important effects.We examined U.S. Renal Data System registry data to study associations of ABOi live-donor kidney transplantation with clinical complications in a national cohort. Among 14,041 Medicare-insured transplants in 2000 to 2007, 119 non-donor-A2 ABOi transplants were identified. A2-incompatible (n=35) transplants were categorized separately. Infection and hemorrhage events were identified by diagnosis codes on billing claims. Associations of ABO incompatibility with complications were assessed by multivariate Cox regression.Recipients of ABOi transplants experienced significantly (P<0.05) higher incidence of wound infections (12.7% vs. 7.3%), pneumonia (7.6% vs. 3.8%), and urinary tract infections (UTIs) or pyelonephritis (24.5% vs. 15.3%) in the first 90 days compared with ABO-compatible recipients. In adjusted models, ABO incompatibility was associated with twice the risk of pneumonia (adjusted hazard ratio [aHR], 2.22; 95% confidence interval [CI], 1.14-4.33) and 56% higher risk of UTIs or pyelonephritis (aHR, 1.56; 95% CI, 1.05-2.30) in the first 90 posttransplantation days, and 3.5 times the relative risk of wound infections in days 91 to 365 (aHR, 3.55; 95% CI, 1.92-6.57). ABOi recipients, 19% of whom underwent pre- or peritransplant splenectomy, experienced twice the adjusted risk of early hemorrhage (aHR, 1.96; 95% CI, 1.19-3.24). A2-incompatible transplantation was associated only with early risk of UTIs or pyelonephritis.ABOi transplantation offers patients with potential live donors an additional transplant option but with higher risks of infectious and hemorrhagic complications. Awareness of these complications may help improve protocols for the management of ABOi transplantation.

| S-EPMC4411309 | biostudies-literature

ABO-incompatible living donor liver transplantation without graft local infusion and splenectomy.

Project description:BackgroundGraft local infusion and splenectomy in ABO-incompatible (ABO-I) living donor liver transplantation (LDLT) are associated with high rates of operative complications.MethodsConsecutive ABO-I LDLT patients treated at the National Cancer Centre between January 2012 and February 2013 were identified. The protocol for ABO-I LDLT at the study centre included the administration of rituximab (300 mg/m(2)) at 2 weeks preoperatively, followed by plasma exchanges (target isoagglutinin titre: ? 1:8), basiliximab (20 mg on the day of surgery and on postoperative day 4), and i.v. immunoglobulin (0.8 g/kg on postoperative days 1 and 4) without graft local infusion or splenectomy.ResultsFifteen patients (11 men and four women) who underwent transplantation for liver cirrhosis (n = 3) or hepatocellular carcinoma (n = 12) were identified. These included 13 patients with hepatitis B virus infection, one with hepatitis C virus infection and one with alcoholic cirrhosis. The mean age, mean Model for End-stage Liver Disease (MELD) score and mean graft-to-recipient weight ratio (GRWR) of these patients was 51.8 years, 11.5 and 0.84, respectively. The median isoagglutinin titre before plasma exchange was 1:32 (range: 1:4 to 1:256). There were no hyperacute or antibody-mediated rejections. No bacterial or fungal infections were observed. Complications included herpes zoster viral infection in one patient, postoperative bleeding in one patient and extrahepatic biliary stricture in three patients.ConclusionsThis simplified ABO-I LDLT protocol showed good graft outcomes without immunologic failure or serious infections.

| S-EPMC4159453 | biostudies-literature

ABO-incompatible deceased donor pediatric liver transplantation: Novel titer-based management protocol and outcomes.

Project description:ABO-ILT have re-emerged as an alternate option for select patients awaiting transplant. However, treatment protocols for children undergoing deceased donor ABO-ILT are not standardized. We implemented a novel IS protocol for children undergoing deceased donor ABO-ILT based on pretransplant IH titers. Children with high pretransplant IH titers (?1:32) underwent an enhanced IS protocol including plasmapheresis, rituximab, IVIG, and mycophenolate, while children with IH titers ?1:16 received steroids and tacrolimus. We retrospectively assessed our outcomes of ABO-ILT with ABO-compatible recipients of similar age and diagnosis over a 2-year period. Ten children with median age of 8.9 months underwent ABO-ILT, 4 of 10 patients underwent enhanced IS due to high IH titers. Rates of complications (rejection, infections, biliary, and vascular) at both 1 year and up to 3 years post-transplant were comparable between the groups. Patients with ABO-ILT had good graft function with 100% survival at a median follow-up of 3.3 years. In conclusion, IS tailored to pretransplant IH titers in pediatric deceased donor ABO-ILT is feasible and can achieve outcomes similar to ABO-CLT at 1 and 3 years post-transplantation.

| S-EPMC6197909 | biostudies-literature

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