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

Ueno, Takayoshi; Zenitani, Masahiro; Yamanaka, Hiroaki; Tanaka, Natsumi; Uehara, Shuichiro; Tazuke, Yuko; Bessho, Kazuhiko; Okuyama, Hiroomi

doi:10.1016/j.transproceed.2016.02.011

Cited by 15 publications

(20 citation statements)

References 17 publications

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“…However, the strength of this study is in the prospective nature of DSA monitoring in a homogeneous patient population. We believe these observations are important because other investigators have shown the clinical significance of dn‐DSAs …”

Section: Discussionmentioning

confidence: 99%

“…Many studies have demonstrated associations between de novo donor‐specific antibody (dn‐DSA) with liver allograft injury . Protocol liver biopsies from pediatric recipients have shown a gradual development of allograft fibrosis in association with anti‐class II DSA . Although deleterious effects of dn‐DSA have been demonstrated, there are sparse data on the risk factors for developing dn‐DSA in the setting of LT. Kaneku et al have shown that patients receiving weaker immunosuppression and with DQ mismatch (MM) are at an increased risk of dn‐DSA formation .…”

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confidence: 99%

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Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

et al. 2018

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Formation of de novo donor-specific antibodies (dn-DSAs) has been associated with longterm immunologic complications after liver transplantation (LT). We hypothesized that human leukocyte antigen (HLA) epitope/eplet mismatch (MM) is a marker of immunogenicity and a risk factor for dn-DSA formation. Sera from 80 LT recipients were prospectively screened for dn-DSA by a Luminex single-antigen test (One Lambda, Inc., Canoga Park, CA) at 1, 2, 3, 6, 12, 18, 24, and 36 months after LT. HLA typing of the recipients and donors was performed using polymerase chain reaction (PCR)-SSP and PCR-SSOP Luminex low-resolution methods (One Lambda, Inc.). The HLAMatchmaker computer algorithm was used for identification of MM eplets at HLA-DRB1 and -DQA1/B1 loci. Luminex single-antigen bead solid phase assay was used for antibody analysis. Standard immunosuppression included thymoglobulin-rituximab induction and tacrolimus maintenance. There were 27 (34%) patients who developed dn-DSA. There were no episodes of antibody-mediated rejection, and 9 (11%) developed acute cellular rejection (ACR). A positive crossmatch status and a higher number of HLA-A, -B, -DR, and -ABDR MMs were not associated with dn-DSA formation. Patients developing dn-DSA had a significantly higher number of total (38 ± 2.7 versus 28 ± 2.3; P = 0.01) and antibody-verified (AbVer; 14 ± 1.1 versus 10 ± 1; P = 0.015) class II MM eplets. By a multivariate regression analysis, the number of class II MM eplets was strongly associated with risk of class II dn-DSA formation (odds ratio [OR], 1.2; P < 0.01). Patients with ACR had a significantly higher number of total (20.2 ± 1.3 versus 13.9 ± 0.9; P < 0.01) as well as AbVer (10.7 ± 1.1 versus 7.5 ± 0.6; P = 0.03) class I MM eplets. In conclusion, donor-recipient HLA epitope MM is associated with a risk of dn-DSA formation and rejection after LT. However, further studies are required to evaluate the clinical utility of epitope matching in LT.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

et al. 2018

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“…The 225 full-text articles were found for possible eligibility with regard to the inclusion criteria. Finally, 15 studies and 2016 patients were included in the final systematic review and meta-analysis, including 5 studies with data on the allograft loss (36)(37)(38)(39)(40), and 10 studies with data on rejection (41)(42)(43)(44)(45)(46)(47)(48)(49)(50). A flow diagram of the article selection process is demonstrated in Figure 1.…”

Section: Study Identification and Characteristicsmentioning

confidence: 99%

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis

et al. 2020

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BackgroundThe impact of de novo anti-HLA donor-specific alloantibodies (DSA) which develop after long-term liver transplantation (LT) remains controversial and unclear. The aim of this study was to investigate the role of de novo DSAs on the outcome in LT.MethodsWe did a systematic review and meta-analysis of observational studies published until Dec 31, 2019, that reported de novo DSA outcome data (≥1 year of follow-up) after liver transplant. A literature search in the MEDLINE/PubMed, EMBASE, Cochrane Library, Scopus and Web of Science Core Collection databases was performed.ResultsOf 5,325 studies identified, 15 fulfilled our inclusion criteria. The studies which reported 2016 liver transplant recipients with de novo DSAs showed an increased complication risk, i.e. graft loss and chronic rejection (OR 3.61; 95% CI 1.94–6.71, P < 0.001; I2 58.19%), and allograft rejection alone (OR 6.43; 95% CI: 3.17–13.04; P < 0.001; I2 49.77%); they were compared to patients without de novo DSAs. The association between de novo DSAs and overall outcome failure was consistent across all subgroups and sensitivity analysis.ConclusionsOur study suggested that de novo DSAs had a significant deleterious impact on the liver transplant risk of rejection. The routine detection of de novo DSAs may be beneficial as noninvasive biomarker-guided risk stratification.

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“…44 DSA have been reported to play a role in inflammation and fibrosis formation. [45][46][47][48] Miyagawa-Hayashino et al 49 evaluated 79 pediatric liver transplant recipients with protocol liver biopsies and detected DSA in 32 individuals (48%); these patients had a higher frequency of bridging fibrosis or cirrhosis (88%) than the DSA-negative patients (17%) did.…”

Section: De Novo Dsa Post-transplantationmentioning

confidence: 99%

Donor-specific HLA Antibodies in Solid Organ Transplantation: Clinical Relevance and Debates

Wang¹,

Wang²,

Wang³

et al. 2019

Exploratory Research and Hypothesis in Medicine

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Both preformed and de novo DSA represent a significant obstacle to transplantation Preformed DSA before transplantation Exposure to "non-self" HLA molecules, as after blood transfusion, pregnancy or sensitization events, can lead to the development of preformed anti-HLA antibodies. 10 Transfusion avoidance or the use of HLA-matched blood may reduce this risk and improve outcomes. 10 Pre-existing sensitization to HLA-DSA may be a contraindication to transplantation due to the increased risk of acute rejection, delayed graft function, and decreased graft survival. 11-15 In support of this observation, pre-transplant DSA significantly

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

Cited by 15 publications

References 17 publications

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

Class II Human Leukocyte Antigen Epitope Mismatch Predicts De Novo Donor‐Specific Antibody Formation After Liver Transplantation

De Novo Donor Specific Antibody and Long-Term Outcome After Liver Transplantation: A Systematic Review and Meta-Analysis

Donor-specific HLA Antibodies in Solid Organ Transplantation: Clinical Relevance and Debates

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