The Significance of Screening for HLA Antibodies in the Long-Term Follow-up of Pediatric Liver Transplant Recipients

Tokodai, Kazuaki; Kawagishi, Naoki; Miyagi, Shigehito; Nakanishi, Chikashi; Hara, Yasuyuki; Fujio, Atsushi; Kashiwadate, Toshiaki; Maida, Kai; Gotō, Hitoshi; Kamei, Takashi; Ohuchi, Noriaki

doi:10.1016/j.transproceed.2015.12.081

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…We detected DSA in 14 out of 50 (28%) patients whereas the reported prevalence ranges from 14% to 55.6% (8–11,17,33,34). In line with other reports, class II DSA were more frequently found than class I DSA (8–11,17,34–37). HLA class II, however, has only limited expression in the microvasculature of the liver, whereas HLA class I is expressed in all hepatocytes.…”

Section: Discussionsupporting

confidence: 92%

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation

Saelens

Biervliet

Velde

et al. 2020

Journal of Pediatric Gastroenterology &Amp; Nutrition

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Objectives: Autoantibodies (AAb) and donor-specific HLA antibodies (DSA) are frequently present in pediatric liver transplant (LT) recipients. Their clinical significance remains incompletely understood. We aimed to investigate the prevalence of serum AAb and DSA in pediatric LT recipients and its correlation with patient characteristics and histological and biochemical parameters.Methods: We retrospectively reviewed the data from 62 pediatric LT patients in follow-up at Ghent University Hospital between January 2007 and February 2018. Blood samples with AAb measurement were taken systematically, liver biopsies (LB) were performed on clinical indication.Results: AAb were detected in 27 (43,3%) patients, with antinuclear antibodies (ANA) being the most frequently (24%) encountered AAb. There was an association between AAb positivity and female gender (p=0,032) and deceased donor LT (p=0,006). Patients with positive AAb underwent a higher number of LB during their follow-up (p<0,001), and an association was found with the presence of non-specific histologic alterations (p=0,032) in the absence of de novo autoimmune hepatitis. Positive AAb were also associated with higher alkaline phosphatase (p<0,001), ALT (p<0,001), AST (p<0,001), γ-GT (p=0,001), IgG (p=0,011) and lower albumin (p=0,029). Fourteen out of 50 (28%) patients were DSA positive, mostly anti-HLA class II. DSA positivity was associated with T cell-mediated rejection (p=0,019), higher total (p=0,033) and direct (p=0,012) bilirubin and γ-GT (p<0,001). Conclusions: The presence of AAb and DSA is associated with histological and biochemical parameters of graft dysfunction. Larger prospective studies are warranted to investigate the Copyright © ESPGHAN and NASPGHAN. All rights reserved. causal relationships between AAb and DSA development and outcome parameters post pediatric LT.

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Section: Discussionsupporting

confidence: 92%

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation

Saelens

Biervliet

Velde

et al. 2020

Journal of Pediatric Gastroenterology &Amp; Nutrition

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“…In addition, de novo DSAs were detected in 60.3%–63% of pediatric LT patients ( 23 , 24 ). In LDLT, 32% of pediatric patients were found to have class II DSA post-transplantation ( 25 ). Thus, approximately half of LDLT pediatric recipients developed DSA in our study, which was comparable to the findings of previous studies.…”

Section: Discussionmentioning

confidence: 99%

Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation

et al. 2023

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The roles of post-transplant anti-HLA donor specific antibody (DSA) in pediatric liver transplantation (LT), including therapeutic strategies, remain controversial. This study aimed to identify the risks of post-transplant DSA for graft fibrosis progression in pediatric living donor LT (LDLT). We retrospectively evaluated 88 LDLT pediatric cases between December 1995 and November 2019. DSAs were assessed with single antigen bead test. Graft fibrosis was histopathologically scored with METAVIR and the centrilobular sinusoidal fibrosis system. Post-transplant DSAs were detected in 37 (52.9%) cases at 10.8 (1.3–26.9) years post-LDLT. The histopathological examination of 32 pediatric cases with post-transplant DSA revealed that 7 (21.9%) with a high DSA-MFI (≥9,378) showed graft fibrosis progression (≥F2). No graft fibrosis was observed in the subjects with a low DSA-MFI. The risk factors for developing graft fibrosis in pediatric cases with post-transplant DSA were an older graft age (>46.5 years old), lower platelet count (<10.7 × 104/ml) and higher Fib4 index (>0.7807, recipient age; >1.8952, donor age). Limited efficacy of additional immunosuppressants was observed in DSA positive pediatric cases. In conclusion, pediatric cases with a high DSA-MFI and risk factors should undergo a histological examination. The appropriate treatment for post-transplant DSA in pediatric LT needs to be determined.

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“…The immunosuppressive regimen was described previously. 18 Patients received induction immunosuppressive treatment consisting of steroids and a CNI with or without basiliximab. Mycophenolate mofetil or azathioprine was added based on the patient’s posttransplant condition.…”

Section: Methodsmentioning

confidence: 99%

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability

Tokodai

Miyagi

Nakanishi

et al. 2017

Transplantation Direct

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BackgroundIn pediatric patients, long-term immunosuppression after liver transplantation (LT) is typically minimal. However, posttransplant donor-specific HLA antibodies (DSAs) may be prevalent under these conditions. Here, we evaluated the effects of minimized calcineurin inhibitor (CNI) on DSA development to assess the validity of minimized/withdrawn immunosuppression.MethodsWe retrospectively examined 66 patients who underwent pediatric LT at our institution between July 1991 and October 2013. Patients were divided into 2 groups based on the CNI trough level. The cutoff trough levels were 3 and 30 ng/mL for tacrolimus and cyclosporine, respectively. Luminex single-antigen bead assays were performed, and the cutoff for a positive reaction was set at a mean fluorescence intensity (MFI) of at least 1000.ResultsThe mean recipient ages at the time of LT were 29.1 and 77.2 months for the low and regular CNI groups, respectively (P = 0.0007). Univariate logistic regression analysis revealed that recipient age at LT younger than 3 years (P = 0.0099) and low CNI (P < 0.0001) were significantly associated with DSA development. In multivariate analysis, low CNI was an independent risk factor of DSA development (P = 0.0011). Of 15 high-MFI DSAs, 3 were anti-DR, and 12 were anti-DQ. Two of 3 anti-DR DSAs and 11 of 12 anti-DQ DSAs had complement-binding ability and high MFIs.ConclusionsCNI minimization was an independent risk factor for posttransplant DSA during long-term follow-up after pediatric LT. Adjusting CNI to appropriate levels is a safe first step to prevent the immunological effects of DSA.

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The Significance of Screening for HLA Antibodies in the Long-Term Follow-up of Pediatric Liver Transplant Recipients

Cited by 9 publications

References 10 publications

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation

Autoantibodies and Donor-specific Antibodies are Associated With Graft Dysfunction in Pediatric Liver Transplantation

Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation

Impact of the Trough Level of Calcineurin Inhibitor on the Prevalence of Donor-Specific Human Leukocyte Antigen Antibodies During Long-Term Follow-Up After Pediatric Liver Transplantation: Antibody Strength and Complement-Binding Ability

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