Impact Of Donor-specific Antibodies Research Articles

Impact of donor-specific antibody with low mean fluorescence intensity on allograft outcomes in kidney transplant

BackgroundImmune-mediated rejection is the most common cause of allograft failure in kidney transplant (KT) patients. Exposure to alloantigen, including human leukocyte antigen (HLA), results in the production of donor-specific antibodies (DSA). There are limited data about low levels of mean fluorescence intensity (MFI) DSA, especially post-transplantation. This study evaluated allograft outcomes in KT patients with low MFI DSA. MethodsFrom January 2007 to December 2021, KT patients who were tested for post-transplant DSA at Ramathibodi Hospital, Bangkok, Thailand, with the DSA MFI ≤ 1000 were evaluated. These KT patients were categorized into two groups: very low DSA (VLL; MFI = 1–500) and low DSA (LL; MFI = 501–1000). All KT patients were evaluated for the primary outcomes, such as the incidence of acute rejection, serum creatinine levels at one and five years after transplantation as well as allograft and patient survivals. ResultsAmong 36 KT patients 25 were included as those with VLL and 11 as those with LL. The LL group had significantly higher T-cell mediated allograft rejection (TCMR) than the VLL group (45% vs. 12%, P = 0.04). In addition, 10 patients, 5 in the VLL group and 5 in the LL group developed antibody-mediated allograft rejection (ABMR). Both TCMR and ABMR were confirmed by biopsy results. There was a trend toward higher MFI in KT patients with ABMR than without ABMR (P = 0.22). At 5 post-transplant years, serum creatinine, allograft and patient survivals were comparable between these two groups. Furthermore, the univariate and multivariate analyzes revealed that the LL group was a high risk for rejection. ConclusionLow MFI DSA values after transplantation may be associated with a higher incidence of rejection, but this finding did not show differences in allograft and patient survival in this study's analysis.

Impact of Donor-Specific Antibodies (DSA) with Low Median Fluorescent Intensity (MFI) on Allograft Outcomes in Kidney Transplant

Impact of Donor-Specific Antibodies (DSA) with Low Median Fluorescent Intensity (MFI) on Allograft Outcomes in Kidney Transplant

(60) Impact of Donor Specific Antibodies in Cardiac Transplant Recipients after Acute Covid-19

(60) Impact of Donor Specific Antibodies in Cardiac Transplant Recipients after Acute Covid-19

(328) Impact of Donor Specific Antibodies on Donor-Derived Cell-Free DNA Levels in Pediatric Heart Transplant Recipients

(328) Impact of Donor Specific Antibodies on Donor-Derived Cell-Free DNA Levels in Pediatric Heart Transplant Recipients

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series.

The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts. We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed. For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact. In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

Antibody-Mediated Rejection in Kidney Transplantation: A Retrospective Study on the Impact of Donor-Specific Antibodies and on the Timing of Diagnosis.

Introduction Limitedinformation exists concerning the clinical significance of histologically confirmed antibody-mediated rejection (h-AMR) without detectable circulating donor-specific antibodies (DSA). In this study, we compared the outcomes of patients with h-AMR according toDSAstatus. Methods A total of 80 kidney transplant (KT) recipients who met the 2018 Banff criteria for h-AMR were included. Clinical and immunological characteristics were evaluated, and outcomes were compared according toDSAstatus after kidney biopsy (KB). Results There were 57 patients who had DSA-positive (+) h-AMR and 23 patients who hadDSA-negative (-) h-AMR. Groups had similar baseline characteristics and time between KT and KB. Concerning histopathological diagnoses/Banff scores,DSA+ patients had higher interstitial fibrosis (ci) and tubular atrophy (ct) (ci+ct) scores and lower arterial hyalinosis (ah) scores compared toDSA- patients. Graft survival (GS) was similar for both groups (64% versus 44% at five years and 44% versus 34% at 10 years).Multivariate analysis revealed the time of KB (less than six months after KT or more than six months after KT) to be associated with GS. A stratified analysis was conducted, targetingDSAstatus according to the time of biopsy. For KB performed less than six months after KT, GS was higher forDSA+ patients at 10 years (66% versus 23%). For KB performed more than six months after KT,DSA- patients had higher GS at 10 years (58% versus 9%). Conclusion Both the timing of AMR diagnosis and DSA status had an impact on AMR outcomes. For patients diagnosed with AMR more than six months after transplantation, GS was worst for those in which circulating DSA were identified. Biopsy specimens from DSA- specimens had higher ct-ci and ah scores.

CT-026 Prevalence and Impact of Donor Specific Anti-HLA Antibodies in the Setting of Myeloablative Haploidentical Transplant for Malignant Hematological Diseases: Single-Center Experience

To study the outcomes, prevalence, and impact of DSA and anti-HLA of myeloablative haploidentical transplant for malignant hematological diseases. We conducted retrospective analysis of our blood and marrow transplant database. We identified 107 patients who received myeloablative haploidentical hematopoietic cell transplantation between January 2013 and December 2020. Sixty-two recipients were male (58%) and 45 were female (48%). The median recipient age was 22 (range: 1-56). Most pairs had matched ABO blood groups (76 pairs [71%]). The graft source was bone marrow in 83 patients (78%). The median infused CD34 cell dose was 4.02×106/kg (range: 1.3-13.1). Sixty-one recipients (57%) had positive anti-HLA; of these, 17 had DSA (15% of the total number of patients, 28% of patients with anti-HLA antibodies). The median cumulative mean fluorescence intensity was 2,062 (IQR: 1,038-6,500). Overall survival, cumulative incidence of relapse, acute graft-versus-host disease, and chronic graft-versus-host disease were comparable between patients with anti-HLA antibodies and those without and between patients with DSA and those without. Recipient and donor gender and recipient/donor gender mismatch showed statistical association with the incidence of anti-HLA antibodies but not DSA. Of the 17 patients with DSA, five underwent desensitization. C1q assay was done pre and post desensitization. Three patients developed GF (2.8%): one was primary (0.9%) due to low CD34 dose, and two had secondary GF (1.9%). None of these cases occurred in patients with anti-HLA antibodies or DSA. The median time from transplant to GF was 2.23 months (range: 0.8-2.89). The median time to absolute neutrophil count and platelet engraftment was 16 days. Our study shows that desensitization may not be required in the setting of myeloablative transplant for malignant hematological disorders. This warrants further investigations in prospective trials.

217.2: A Multi-institutional Study of Factors Determining Cardiac Allograft Function in Children at 3 Years Post-transplant: Absence of Impact of Donor Specific Antibodies

217.2: A Multi-institutional Study of Factors Determining Cardiac Allograft Function in Children at 3 Years Post-transplant: Absence of Impact of Donor Specific Antibodies

The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure.

Donor-specific antibodies (DSA) against HLA are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid-organ transplant recipients. However, the impact of DSA with or without histopathological evidence of rejection among pancreas transplant recipients (PTRs) is unknown. In this study, we included all PTRs at our center between 2005 and 2020, with pancreas allograft biopsy before March 31, 2021, and with DSA checked within 15 d of the biopsy. PTRs were divided into 4 groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-, Rej+/DSA-, Rej-/DSA+, and Rej+/DSA+. Two hundred two PTRs had a pancreas allograft biopsy during the study period. Thirty-nine were in Rej-/DSA-, 84 Rej+/DSA-, 24 Rej-/DSA+, and 55 Rej+/DSA+. The mean interval from transplant to index biopsy was not statistically different between the 4 groups. The most common type of rejection was T cell-mediated rejection; however, antibody-mediated rejection was more prevalent in the Rej+/DSA+ group. At 5 y postbiopsy, the rate of death-censored graft failure (DCGF) for Rej-/DSA- was 18%, 24% in Rej+/DSA-; 17% in Rej-/DSA+ and 36% in Rej+/DSA+ (P = 0.14). In univariate analysis, mixed rejection (hazard ratio [HR], 3.0; 95% confidence intervals [CI], 1.22-7.39; P = 0.02) along with solitary pancreas transplantation and Rej+/DSA+ were associated with DCGF. In multivariate analysis, compared with Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR, 2.32; 95% CI, 1.03-5.20; P = 0.04); however, Rej+/DSA- was not (HR, 1.06; 95% CI, 0.32-3.56; P = 0.92). PTRs with pancreas allograft rejection and concomitant DSA have an increased risk of DCGF.

208.1: The Presence of Donor-specific Antibodies Around the Time of Pancreas Graft Biopsy With Rejection Is Associated With an Increased Risk of Graft Failure

Introduction: Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) are an important biomarker predicting graft injury, rejection (Rej), and failure in various solid organ transplant recipients. However, the impact of DSA with or without Rej among pancreas transplant recipients (PTRs) is unknown. Method: In this study, we included all PTRs who had undergone either simultaneous pancreas-kidney or solitary pancreas transplant at our center between 2005 and 2020, with pancreas allograft biopsy before 03/2021, and with DSA checked within 15 days of the biopsy. Among PTRs with multiple biopsies during the study period, the first index biopsy was used to analyze the data. Pancreas biopsies at the time of implant or explant were excluded, as were biopsies with no pancreas tissue present. PTRs were divided into four groups based on the biopsy findings on the index biopsy and DSA status as Rej-/DSA-; Rej+/DSA-; Rej-/DSA+ and Rej+/DSA+. Results: A total of 352 pancreas allograft biopsies were performed in 203 PTRs during the study period. Of these, 203 PTRs, 41 were in Rej-/DSA-; 87 Rej+/DSA-; 24 Rej-/DSA+; and 51 Rej+/DSA+. Most of the baseline characteristics were similar between the groups, except PTRs in Rej-/DSA+ and Rej+/DSA+ were relatively younger, with a mean age of 39 compared to 43 for the other two groups. The mean interval from transplant to index biopsy was not statistically different between the four groups. The most common rejection was TCMR, however, AMR was more prevalent in the Rej+/DSA+ group. In addition, DSA against class II HLA was more prevalent in the DSA+/Rej + group. There was no statistical difference in the mean post index biopsy follow-up. At last follow up, the rate of death censored graft failure (DCGF) for Rej-/DSA- was 22%, 29% in Rej+/DSA-; 17% in Rej-/DSA+ and 39% in Rej+/DSA+. Although not statistically significant, there was a trend towards inferior pancreas graft survival in Rej+/DSA+ group by unadjusted K-M survival analysis (Figure 1).In multivariable analysis compared to Rej-/DSA-, Rej+/DSA+ was significantly associated with DCGF (HR: 2.25, 95% CI: 1.02 to 4.97; p=0.04), however Rej+/DSA- was not (HR: 1.40; 95% CI: 0.65 to 3.0; p=0.39). Conclusions: PTRs with pancreas allograft rejection in the presence of DSA have an increased risk of DCGF, and may warrant particularly aggressive management.

Impact of donor-specific antibodies on long-term graft survival with pediatric liver transplantation.

BACKGROUNDIn a previous paper, we reported a high prevalence of donor-specific antibody (DSA) in pediatric patients with chronic rejection and expressed the need for confirmation of these findings in a larger cohort.AIMTo clarify the importance of DSAs on long-term graft survival in a larger cohort of pediatric patients.METHODSWe performed a retrospective analysis of 123 pediatric liver transplantation (LT) recipients who participated in yearly follow-ups including Luminex testing for DSA at our center. The cohort was split into two groups according to the DSA status (DSA-positive n = 54, DSA-negative n = 69). Groups were compared with regard to liver function, biopsy findings, graft survival, need for re-LT and immunosuppressive medication.RESULTSDSA-positive pediatric patients showed a higher prevalence of chronic rejection (P = 0.01), fibrosis (P < 0.001) and re-transplantation (P = 0.018) than DSA-negative patients. Class II DSAs particularly influenced graft survival. Alleles DQ2, DQ7, DQ8 and DQ9 might serve as indicators for the risk of chronic rejection and/or allograft fibrosis. Mean fluorescence intensity levels and DSA number did not impact graft survival. Previous episodes of chronic rejection might lead to DSA development.CONCLUSIONDSA prevalence significantly affected long-term liver allograft performance and liver allograft survival in our cohort of pediatric LT. Screening for class II DSAs in combination with assessment of protocol liver biopsies for chronic antibody-mediated rejection improved early identification of patients at risk of graft loss.

Essential updates 2018/2019: Liver transplantation.

Among the recent topics in the field of liver transplantation (LT), one of the significant therapeutic breakthroughs is the introduction of direct‐acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection. With cure rates close to 100%, a better proportion of LT candidates and recipients can be cured of HCV infection by DAA therapies that are simple and well‐tolerated. Other critical topics include the issue of indication of LT for patients with hepatocellular carcinoma, which has been continuously studied. Several expanded criteria beyond the Milan criteria with acceptable results have been recently reported. The role of donor‐specific antibodies (DSAs) in intractable rejection is also an important matter that has been studied. Although long recognized as an important factor in antibody‐mediated rejection and even graft survival in renal transplantation, the impact of DSAs on graft and patient survival in LT remains to be elucidated. Including the issues described above, this article focuses on recent advances in LT, management to avoid recurrence of primary diseases, optimization of immunosuppressive treatment, and extended donor criteria.

Prognostic factors for renal transplant graft survival in a retrospective cohort of 1000 cases: The role of desensitization therapy

To review the results of renal transplantation after promulgation of the Human Organ Transplant Act in Taiwan in 1987, we conducted a retrospective study in the first 1000 cases performed in our hospital. Prognostic factors for graft survival were assessed with emphasis on the impact of donor-specific antibody (DSA). Between January 1988 and April 2014, there were 1000 cases of renal transplantation performed in our hospital. Excluding 30 patients of ABO-incompatible transplantation, we reviewed 970 cases of ABO-compatible renal transplantation to analyze the prognostic factors for graft survival. The patients were grouped according to the dates of operations before (the Early group: 503 cases) and after (the Late group: 467 cases) the introduction of detection and desensitization of alloantibody in our hospital in 2004. The overall 5-year graft survival rate were 82.6%, which was significantly lower in the Early group (79.2%) than the Late group (86.3%) (p=0.0012). The 1-year rejection-free survival was significantly lower in the Early group (78.3%) than the Late group (91.2%) (p=0.0165). The difference between the two groups became insignificant when the time of observation extended beyond 12 months. In a multivariate regression model, we identified significant factors for poor graft survival, including HLA mismatches, delayed graft function with or without recovery, and antibody-mediate rejection (AMR). HLA mismatches, delayed graft function with or without recovery, and AMRwere significant factors for poor graft survival. Detection and desensitization of DSA currently might be inadequate to improve the long-term outcome of renal transplantation.

OR23 The impact of donor specific antibody in antibody mediated rejection and acute cellular rejection of kidney allografts after simultaneous liver-kidney transplantation

OR23 The impact of donor specific antibody in antibody mediated rejection and acute cellular rejection of kidney allografts after simultaneous liver-kidney transplantation

350.6: The impact of circulating DSA in visceral transplant recipients without histological evidence of rejection: How should we treat or not treat?

Backgrounds: There has been accumulating evidence that donor-specific antibody (DSA) has a negative impact on the outcome of visceral allografts. Prospective DSA monitoring allows detection of circulating DSA without histological evidence of acute rejection. However, its association with acute rejection and natural course without treatment are yet to be determined. Methods: Between 2012 and 2019, 94 visceral transplantation with 25 liver-contained grafts were performed at a single institution. Induction therapy for preformed DSA included rituximab or bortezomib. DSA were monitored at 1 and 2weeks, followed by 1, 3, and 6 months, and yearly after transplant. De-novo DSA was not treated without histologically proved rejection. The characteristics and impact of DSA in terms of predictability of rejection, and its correlation of severity of acute rejection were analyzed. Results: One-year cumulative rejection rate in the entire cohort was 67%. With the protocol of anti-B cell therapy, preformed DSA did not increase the risk of rejection, regardless of the status of liver-free allografts, high titer (>4000 MFI) or persistence of DSA. Moreover, there was no difference in severity of rejection with the presence of preformed DSA (n=12) compared to that without DSA (n=36). However, 3-years graft survival was inferior in patients with preformed DSA to those without (52% vs. 64%, p=0.069), due to increased infectious complications. De-novo DSA was detected in 32 patients (35%) with an HLA-ABDR mismatch as the only predictor (Odds ratio 1.7, p=0.036). De-novo DSAs were more likely to be class II with high inclusion of anti-DQ DSA (69%). Prospective monitoring detected de-novo DSA in 25 occasions without ongoing rejection. Accordingly, it turned negative without rejection episode in 19 (76%) (Silent DSA), while subsequent rejection occurred in 6 occasions (24%) (DSA before rejection). In 10 occasions, de-novo DSA turned positive during the rejection episodes (DSA during rejection). The rejection episodes that induced DSA circulation was with a more severe grade. Conclusions: Increased immunosuppressant induction to treat preformed DSA may compensate the rejection risk, but can negatively impact the overall graft survival. With prospective monitoring and no preemptive treatment, high proportion of de-novo DSA was self-limiting, and rarely precipitated rejection episodes particularly with a severe grade.

Impact of donor specific antibodies on biliary complication after living donor liver transplantation

Impact of donor specific antibodies on biliary complication after living donor liver transplantation

Limited impact of pre-existing donor specific HLA-antibodies (DSA) on long term allograft survival after first adult liver transplantation

The relevance of pre-existing HLA-antibodies (HLA-Ab) in liver transplantation (LTx) is controversial. While livers are allocated without HLA match or preoperative crossmatch testing, several studies point to an impact of donor specific antibodies (DSA) for acute rejection, bile duct complications or even graft loss.To investigate the role of DSA in long term liver allograft survival we analysed 177 pre transplant sera of first LTx patients with Luminex single antigen technology defining a MFI of >1500 as positive. The analyses were done retrospectively, and the DSA results had no impact on graft acceptance or patients’ therapy. Three year follow up was available for all patients.77% of our patients had any HLA-Ab pre transplantation, 55 patients were transplanted with DSA by chance.Acute rejections or ischemic type bile duct lesions (ITBL) were not higher in the DSA group, but ITBL was associated with a higher donor age. There was no difference in long term graft function or survival in patients without HLA-Ab, with non DSA or with DSA (p = 0.712).We suggest that determination of pre-existing DSA in first LTx recipients is not appropriate and we conclude that pre-existing DSA in first LTx patients are not a contraindication for liver transplantation.

P002 Patient outcomes following liver-kidney transplantation with donor specific antibodies

Aim Simultaneous liver and kidney transplantation (SLKT) remains as the gold standard for patients with chronic renal and liver diseases. Pre-transplant donor-specific antibody (DSA) to class I antigens have been shown to decrease following SLKT; whereas, DSA to class II antigens may remain detrimental to long term graft survival. Methods We analyzed a cohort of SLKT performed at our institution from 2011 to 2017. We ran both flow and cytotoxic crossmatches pre-transplant and crossmatch positive samples were rerun in the post transplant period. We monitored for DSA both pre and post transplant using a single antigen bead assay. (One Lambda). Results There were 30 SLKT performed, of which 11 had pre-formed DSA (four class I and II DSA, five class I DSA only, two class II only). Strong donor specific anti-HLA antibodies were eliminated following SLKT for class I and II specificities while preserving anti-HLA antibodies against antigens that were not expressed on the donor. The presence of DSA lead to six positive flow cytometry crossmatches of which three were cytotoxic crossmatch positive. Repeat crossmatching with recipient serum post SLKT was found to be negative which correlated with the sharp decrease in DSA MFI detectable in recipient serum. Whether DSA in recipient serum was against class I, II or both antigens there was no significant difference in one-year patient or graft survival. Conclusions The liver absorbed the impact of DSA in our cohort of SLKT recipients. The SLKT recipient did well following transplant in the presence of DSA to class I, II or both. Given the high priority SLK patients receive, having strong DSA no matter the class with a positive XM result should not be a contraindication to transplant.

Impact of Donor-Specific Antibodies on Graft Fibrosis After Pediatric Living Donor Liver Transplantation for Biliary Atresia

BackgroundPediatric living donor liver transplant (LDLT) patients sometimes develop graft fibrosis after non-recurrent diseases such as biliary atresia (BA). Donor-specific antibodies (DSA) have recently been shown to play a possible role in graft damage after liver transplantation. We report the impact of DSA on pediatric LDLT for BA patients. MethodsPatients under age 18 years who received LDLT for BA at our institution and who had at least 5 years' follow-up were identified, and 23 were eventually enrolled in this study. Pathological findings were assessed with the use of the last available biopsy. Patients were divided into 2 groups, DSA-positive and DSA-negative. Graft fibrosis after LDLT was assessed according to DSA groups. ResultsThe mean patient age at transplant was 2.6 years. The mean time to the last available biopsy after LDLT was 8.2 years (4.8–15.6 years); 6 patients (26%) showed no fibrosis, whereas fibrosis was graded as F1, F2, or F3 in 8 patients (35%), 8 patients (35%), and 1 patient, respectively. DSA were observed in 12 patients (52%). Moderate graft fibrosis (F2 and F3) was found in 7 (58%) of the DSA-positive group, but only 2 (18%) of the DSA-negative group, showing a statistically significant difference (P < .05). Pre-transplant cross-matching was performed in 17 patients. The 2 patients with a positive cross-match were DSA-positive. Six cross-match–negative patients developed de novo DSA after LDLT. ConclusionsGraft fibrosis was observed after LDLT for BA during long-term follow-up, more commonly in DSA-positive patients. DSA may play a role in fibrosis formation.

(554) - The Impact of Donor Specific Antibodies on Antibody Mediated Rejection

(554) - The Impact of Donor Specific Antibodies on Antibody Mediated Rejection