Clinical Relevance of HLA Antibody Monitoring after Kidney Transplantation

Morath, Christian; Opelz, Gerhard; Zeier, Martin; Süsal, Caner

doi:10.1155/2014/845040

Cited by 43 publications

(45 citation statements)

References 29 publications

(40 reference statements)

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“…All patients enrolled in our study were negative for donor-specific antibodies (DSA), as the presence of donor-specific anti-human leukocyte antigen (HLA) antibodies is associated with antibody-mediated rejection [9]. At biopsy, all patients were receiving immunosuppressive therapy that consisted of corticosteroids, calcineurin inhibitors (tacrolimus or cyclosporin) and everolimus or mycophenolate mofetil.…”

Section: Kidney Biopsy Samplesmentioning

confidence: 99%

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Curci

Sallustio

Serino

et al. 2016

Nephrol. Dial. Transplant.

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Background. Chronic T cell-mediated rejection (TCMR) in kidney graft is characterized by reduction of the vessel lumen with marked intimal thickening, fibrous hyperplasia of the small renal arteries and leukocyte infiltrates. The aim of this study was to find specific gene expression profiles in chronic TCMR kidney biopsies. Methods. RNA extracted from archival formalin-fixed, paraffinembedded renal biopsies was used for gene expression profiling. Our study included 14 patients with chronic TCMR and 10 with acute TCMR. Fifty-two cadaveric donors were used as controls. The results were validated in an independent set of kidney biopsies. Results. We identified 616 and 243 differentially expressed genes with a fold change ≥1.5 and a false discovery rate <0.05 in chronic and acute TCMR, respectively. Pathway analysis revealed upregulation of OX40 signalling. This pathway is involved in the generation of CD8 + effector memory T cells and the upregulation of killer cell lectin-like receptor G1 (KLRG-1), B lymphocyte-induced maturation protein 1 (BLIMP-1) and CD25, which characterize CD8 + effector memory T cells.

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Section: Kidney Biopsy Samplesmentioning

confidence: 99%

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Curci

Sallustio

Serino

et al. 2016

Nephrol. Dial. Transplant.

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“…Given the importance of AMR in causing acute graft dysfunction 11 and the negative correlation of DSA with long-term allograft survival for both cell and organ transplants 7-9,35-38 , it is of great interest to devise optimal maintenance immunosuppression to suppress the emergence of DSA posttransplant. The clinical literature includes publications which report that no current immunosuppressive regimens effectively prevent the development of DSA 10,11 , while others infer relative efficacy of CNi by reporting that conversion of kidney transplant recipients from CNi to mTORi-based therapy is associated with a negative impact on DSA production and graft survival 19,39-41 .…”

Section: Discussionmentioning

confidence: 99%

mTOR Inhibition Suppresses Posttransplant Alloantibody Production Through Direct Inhibition of Alloprimed B Cells and Sparing of CD8+ Antibody-Suppressing T cells

et al. 2016

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Background De novo alloantibodies (DSA) contribute to antibody-mediated rejection and poor long-term graft survival. Since the development of DSA is associated with early graft loss of cell transplants and reduced long-term survival of solid organ transplants, we hypothesized that conventional immunosuppressives, calcineurin inhibitors (CNi) and mammalian target of rapamycin inhibitors (mTORi), may not be as effective for suppression of humoral alloimmunity as for cell-mediated immunity. Methods Wild-type or CD8-depleted mice were transplanted with allogeneic hepatocytes. Recipients were treated with mTORi and/or CNi and serially monitored for alloantibody and graft survival. The direct effect of mTORi and CNi on alloprimed B cell function was investigated in Rag1-/- mice adoptively transferred with alloprimed IgG1+ B cells. The efficacy of mTORi and/or CNi to suppress CD8-mediated cytotoxicity of IgG1+ B cells was evaluated in in vitro and in vivo cytotoxicity assays. Results mTORi, but not CNi, reduced alloantibody production in transplant recipients, directly suppressed alloantibody production by alloprimed IgG1+ B cells and delayed graft rejection in both low and high alloantibody-producers. Combination treatment with mTORi and CNi resulted in loss of the inhibitory effect observed for mTORi monotherapy in part due to CNi-suppression of CD8+ T cells which downregulate alloantibody production (CD8+ TAb-supp cells). Conclusions Our data supports that mTORi is a potent inhibitor of humoral immunity through suppression of alloprimed B cells and preservation of CD8+ TAb-supp cells. In contrast, alloantibody is readily detected in CNi-treated recipients because CNi does not suppress alloprimed B cells and interferes with downregulatory CD8+ TAb-supp cells.

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“…However, the morbidity rate is high during the early post‐transplant period and severe complications frequently result in patient death . Donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) are related to graft loss and chronic rejection due to humoral rejection in patients who have undergone kidney, lung, or heart transplantation . In contrast, liver transplant recipients have historically been considered highly resistant to DSAs.…”

Section: Introductionmentioning

confidence: 99%

“…3 Donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are related to graft loss and chronic rejection due to humoral rejection in patients who have undergone kidney, lung, or heart transplantation. [4][5][6][7] In contrast, liver transplant recipients have historically been considered highly resistant to DSAs. In recent years, Luminex analysis (HLA Laboratory, Kyoto, Japan) using the single antigen bead technique has been established as an accurate method for measuring anti-HLA antibodies.…”

Section: Introductionmentioning

confidence: 99%

Preformed donor‐specific antibodies are associated with 90‐day mortality in living‐donor liver transplantation

Tamura

Tohyama

Watanabe

et al. 2019

Hepatology Research

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Aim The impact of donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) on living donor liver transplantation (LDLT) is unclear. The aim of this study was to investigate the association between DSAs and short‐term outcomes in LDLT recipients, and to clarify the clinical impact of DSAs. Method Anti‐HLA antibodies were screened in preoperative serum samples taken from 40 liver transplant recipients at Ehime University (Toon, Japan) between August 2001 and July 2015. Screening was carried out using the Flow‐PRA method, and DSAs were detected in anti‐HLA antibody‐positive recipients using the Luminex single‐antigen identification test. A mean fluorescence intensity of 1000 was used as the cut‐off for positivity. We retrospectively reviewed the clinical courses of patients who were DSA‐positive to elucidate early clinical manifestations in LDLT recipients. Results Fifteen (12 female and 3 male) patients (38%) had anti‐HLA antibodies. Eight of the 15 anti‐HLA antibody‐positive patients were positive for DSAs, and all were women. The 90‐day survival rate of DSA‐positive patients (50%) was significantly lower than that of DSA‐negative patients (84.4%) (0.0112; Wilcoxon test). On univariate analysis, the DSA‐positive rate was significantly higher in the 90‐day mortality group. Postoperatively, the incidence of acute cellular rejection was higher in DSA‐positive than DSA‐negative patients. Thrombotic microangiopathy developed only in DSA‐positive patients. We found no relationship between DSA status and bile duct stricture. Conclusion Preformed DSAs could be associated with elevated 90‐day mortality in LDLT recipients. Further large‐scale studies are required to verify the risk associated with DSAs in LDLT.

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Clinical Relevance of HLA Antibody Monitoring after Kidney Transplantation

Cited by 43 publications

References 29 publications

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

Potential role of effector memory T cells in chronic T cell-mediated kidney graft rejection

mTOR Inhibition Suppresses Posttransplant Alloantibody Production Through Direct Inhibition of Alloprimed B Cells and Sparing of CD8+ Antibody-Suppressing T cells

Preformed donor‐specific antibodies are associated with 90‐day mortality in living‐donor liver transplantation

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