Donor‐specific anti‐<scp>HLA</scp> antibodies are not associated with nonanastomotic biliary strictures but both are independent risk factors for graft loss after liver transplantation

Dulk, A. Claire den; Shi, Xianbo; Verhoeven, Cornelia J.; Dubbeld, Jeroen; Claas, Frans H.J.; Wolterbeek, Ron; Brand-Schaaf, Simone H.; Verspaget, Hein W.; Sarasqueta, Arantza Fariña; Laan, Luc J. W. van der; Metselaar, Herold J.; Hoek, Bart van; Kwekkeboom, Jaap; Roelen, Dave L.

doi:10.1111/ctr.13163

Cited by 16 publications

(12 citation statements)

References 44 publications

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“… 46–49 Den Dulk et al showed that both non-anastomotic strictures (NAS) and de novo Class II donor-specific antibodies against donor human leukocyte antigen after liver transplantation are independent factors associated with graft loss. 50 The extent of the inflammation could be influenced by silent humoral and cellular mechanisms and needs to be investigated in further studies. 51 The significant association of circulating donor-specific antibodies against donor human leukocyte antigen with histological inflammation described in our study seems to occur without apparent fibrosis.…”

Section: Discussionmentioning

confidence: 99%

“…Associations between humoral alloreactivity and biliary complications have been described in the literature. [46][47][48][49] Den Dulk et al showed that both nonanastomotic strictures (NAS) and de novo Class II donorspecific antibodies against donor human leukocyte antigen after liver transplantation are independent factors associated with graft loss. 50 The extent of the inflammation could be influenced by silent humoral and cellular mechanisms and needs to be investigated in further studies.…”

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confidence: 99%

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Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies

Gül‐Klein¹,

Hegermann²,

Röhle³

et al. 2021

JIR

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Background Donor-specific antibodies (DSA) against donor human leukocyte antigen after liver transplantation, which are associated with histological changes, have been widely studied with respect to their sustained impact on transplant function. However, their long-term impact after liver transplantation remains unclear. Methods We performed a cross-sectional analysis from June 2016 to July 2017 that included all patients who presented themselves for scheduled follow-up after receiving a liver transplantation between September 1989 and December 2016. In addition to a liver protocol biopsy, patients were screened for human leukocyte antigen antibodies (HLAab) and donor-specific antibodies. Subsequently, the association between human leukocyte antigen antibodies, donor-specific antibodies, histologic and clinical features, and immunosuppression was analyzed. Results Analysis for human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was performed for 291 and 271 patients. A significant association between higher inflammation grades and the presence of human leukocyte antigen antibodies and donor-specific antibodies was detected, while fibrosis stages remained unaffected. These results were confirmed by multivariate logistic regression for inflammation showing a significant increase for presence of human leukocyte antigen antibodies and donor-specific antibodies (OR: 4.43; 95% CI: 1.67–12.6; p=0.0035). Furthermore, the use of everolimus in combination with tacrolimus was significantly associated with the status of negative human leukocyte antigen antibodies and donor-specific antibodies. Viral etiology for liver disease, hepatocellular carcinoma (HCC) and higher steatosis grades of the graft were significantly associated with a lower rate of human leukocyte antigen antibodies. The impact of human leukocyte antigen antibodies and donor-specific antibodies against donor human leukocyte antigen was associated with higher levels of laboratory parameters, such as transaminases and bilirubin. Conclusion Donor-specific antibodies against donor human leukocyte antigen are associated with histological and biochemical graft inflammation after liver transplantation, while fibrosis seems to be unaffected. Future studies should validate these findings for longer observation periods and specific subgroups.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies

Gül‐Klein¹,

Hegermann²,

Röhle³

et al. 2021

JIR

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“…83,84 Although the presence of donorspecific antibodies (DSAs) has not been examined specifically with regards to rPSC development, there is no robust association between preformed or de novo DSA with the development of NASs, despite an association of DSA with rejection and shorter graft survival after transplant. 85 One study observed that PSC patients who underwent ABOincompatible LT treated with rituximab retained excellent graft function for more than 7 years without recurrence of PSC. This is in comparison to both patients who underwent ABO-compatible transplants and patients who underwent ABO-incompatible transplants who were not treated with rituximab; thus, the authors suggest that reduced rPSC risk may be mediated by depletion of memory B cells and induction of tolerance in replenishing immature B cells.…”

Section: Immunologic Factors: Human Leukocyte Antigen Donor-specific Alloantibodies and Acute Cellular Rejectionmentioning

confidence: 99%

Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions

et al. 2021

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Patients with primary sclerosing cholangitis (PSC) constitute 5 to 15% of patients listed for liver transplantation worldwide. Although post-transplant outcomes are favorable, recurrent PSC (rPSC) occurs in an important subset of patients, with higher prevalence rates reported with increasing time from transplant. Given its association with poor graft outcomes and risk of retransplant, effort has been made to understand rPSC, its pathophysiology, and risk factors. This review covers these facets of rPSC and focuses on implicated risk factors including pretransplant recipient characteristics, inflammatory bowel-disease-related factors, and donor-specific and transplant-specific factors. Confirming a diagnosis of rPSC requires thoughtful consideration of alternative etiologies so as to ensure confidence in diagnosis, management, subsequent risk assessment, and counseling for patients. Unfortunately, no cure exists for rPSC; however, future large-scale efforts are underway to better characterize the natural history of rPSC and its associated risk factors with hopes of identifying potential key targets for novel therapies.

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“…(78) There is some variability among studies regarding 1-year dnDSA prevalence in LTRs ranging from 8.1% to 24.3%. (75,76,78,79) The variability is likely affected by donor type, number of mismatched HLA loci studied, mean fluorescence intensity (MFI) cutoff for positivity, rate of ACR, and IST regimen. Reports of longterm (ranging from 34 months to 7 years) dnDSA prevalence in LTRs also widely vary ranging from 14.0% to 44.4%, although all showed that dnDSA were produced mostly against HLA-2 antigens, especially HLA-DQ antigens.…”

Section: Donor-specific Antibodiesmentioning

confidence: 99%

“…(77,78,80,81) Studies seem to agree on an association between dnDSA and rejection in deceased donor LTRs, and the potential pathogenicity of HLA-DQ dnDSA in LTRs. (73,75,76,79) The controversy regarding the impact of pfDSA on outcomes for LTRs persists.…”

Section: Donor-specific Antibodiesmentioning

confidence: 99%

Genomics and Liver Transplantation: Genomic Biomarkers for the Diagnosis of Acute Cellular Rejection

2020

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Acute cellular rejection (ACR) is a common complication in liver transplantation recipients (LTRs), especially within the first 12 months, and it is associated with increased morbidity and mortality. Although abnormalities in standard liver biochemistries may raise the clinical suspicion for ACR, it lacks specificity, and invasive liver biopsies, which are associated with numerous risks, are required for definitive diagnoses. Biomarker discovery for minimally invasive tools for diagnosis and prognostication of ACR after liver transplantation (LT) has become a rapidly evolving field of research with a recent shift in focus to omics‐based biomarker discovery. Although none are yet ready to replace the standard of care, there are several promising minimally invasive, blood‐derived biomarkers that are under intensive research for the diagnosis of ACR in LTRs. These omics‐based biomarkers, encompassing DNA, RNA, proteins, and metabolites, hold tremendous potential. Some are likely to become integrated into ACR diagnostic algorithms to assist clinical decision making with a high degree of accuracy that is cost‐effective and reduces or even obviates the need for an invasive liver biopsy.

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Donor‐specific anti‐HLA antibodies are not associated with nonanastomotic biliary strictures but both are independent risk factors for graft loss after liver transplantation

Cited by 16 publications

References 44 publications

Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies

Donor-Specific Antibodies Against Donor Human Leukocyte Antigen are Associated with Graft Inflammation but Not with Fibrosis Long-Term After Liver Transplantation: An Analysis of Protocol Biopsies

Recurrent Primary Sclerosing Cholangitis: Current Understanding, Management, and Future Directions

Genomics and Liver Transplantation: Genomic Biomarkers for the Diagnosis of Acute Cellular Rejection

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