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Jon A. Kobashigawa - One of the best experts on this subject based on the ideXlab platform.

  • Association of vimentin Antibody and other non-HLA antibodies with treated Antibody Mediated Rejection in heart transplant recipients.
    Human Immunology, 2020
    Co-Authors: Xiaohai Zhang, Michelle M. Kittleson, Jignesh Patel, Ryan Levine, Lawrence S.c. Czer, Jon A. Kobashigawa
    Abstract:

    Abstract Non-human leukocyte antigen (HLA) antibodies have been implicated in heart transplantation Rejection. However, targets of non-HLA antibodies remain elusive. Here, we utilized a panel of multiplex beads-based assay to determine the specificity of non-HLA antibodies following heart transplantation. We utilized a selected cohort of recipients who did not have HLA donor specific antibodies, but were diagnosed with Antibody Mediated Rejection and treated for Antibody Mediated Rejection. We found the presence of vimentin Antibody was associated with treated Antibody Mediated Rejection. Our results suggest that, in heart transplant recipients who are suspected of AMR but in the absence of HLA donor specific antibodies, non-HLA antibodies should be examined.

  • Abstract 9639: Pre-Transplant Circulating Antibodies Predict Development of Antibody-Mediated Rejection after Heart Transplant Using the New ISHLT Antibody-Mediated Rejection Pathology Grading Scale
    Circulation, 2012
    Co-Authors: Michelle M. Kittleson, Nancy L Reinsmoen, Jignesh Patel, Matthew Rafiei, Antoine Hage, L. Stern, Fardad Esmailian, Jon A. Kobashigawa
    Abstract:

    Purpose: Pre-transplant circulating antibodies have been associated with the development of Antibody Mediated Rejection (AMR) following heart transplantation. The new pathology Antibody Mediated re...

  • Antibody-Mediated Rejection
    Current opinion in organ transplantation, 2012
    Co-Authors: Michelle M. Kittleson, Jon A. Kobashigawa
    Abstract:

    PURPOSE OF REVIEW The diagnosis of Antibody-Mediated Rejection (AMR) has been revolutionized in recent years by advances in the detection of human leukocyte antigen (HLA) and non-HLA antibodies and by the standardized classification of histologic and immunologic changes in endomyocardial biopsies. The treatment of AMR is also undergoing significant development with targeted use of therapies directed at Antibody production and function. RECENT FINDINGS The diagnosis of AMR achieved greater standardization after a consensus conference in 2010. By the proposed classification, endomyocardial biopsies are now graded on the basis of the severity of histologic and immunologic changes. Management of AMR is often complicated, as patients may have persistent symptoms after treatment, including a reduction in ejection fraction, restrictive physiology leading to recurrent heart failure, and accelerated progression of transplant coronary artery disease. We often rely on therapies to reduce the levels of donor-specific anti-HLA antibodies, including rituximab and bortezomib, as well as photopheresis to alter the function of T cells, although such patients may go on to require redo transplantation. SUMMARY AMR offers challenges of diagnosis and management, but recent advances in the detection of antibodies, the interpretation of endomyocardial biopsies, and the use of therapies directed toward Antibody production offer great promise. In the future, standardization of management across transplant centers will allow for clinical trials of the effectiveness of these therapies.

Richard J. Marcus - One of the best experts on this subject based on the ideXlab platform.

  • Treatment of Antibody-Mediated Rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen.
    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2012
    Co-Authors: Janice G. Nigos, Swati Arora, Parineesha Nath, Sabiha M Hussain, Richard J. Marcus, Kalathil K Sureshkumar
    Abstract:

    OBJECTIVES Antibody-Mediated Rejection after kidney transplant is less responsive to conventional antiRejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe Antibody-Mediated Rejection. MATERIALS AND METHODS A retrospective chart review was performed on patients with biopsy-proven Antibody-Mediated Rejection after kidney transplant at our institution over 12 months. Diagnosis of Antibody-Mediated Rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute Rejection or positive donor-specific Antibody titers. Treatment for Antibody-Mediated Rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m²) along with bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Antibody-Mediated Rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol. RESULTS Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy. CONCLUSIONS In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific Antibody titers and stable renal function in patients experiencing severe Antibody-Mediated Rejection.

  • Antibody-Mediated Rejection following renal transplantation
    Expert opinion on pharmacotherapy, 2007
    Co-Authors: Kalathil K Sureshkumar, Sabiha M Hussain, Barbara J Carpenter, Stephen Sandroni, Richard J. Marcus
    Abstract:

    Antibody-Mediated Rejection (AMR) accounts for 20 – 30% of all acute Rejection episodes following renal transplantation. AMR is generally less responsive to conventional anti-Rejection therapy, resulting in poor allograft survival. Introduction of C4d immunostaining of renal allograft biopsies and the demonstration of donor-specific antibodies in the recipients have increased our ability to diagnose AMR. Therapeutic options are evolving and include plasmapheresis, intravenous immunoglobulin, immunoadsorption and rituximab, together with intensification of immunosuppression with a tacrolimus/mycophenolate mofetil combination. Future studies might further define optimal therapeutic approach in renal transplant recipients presenting with AMR.

Priya S Verghese - One of the best experts on this subject based on the ideXlab platform.

  • bortezomib in the treatment of Antibody Mediated Rejection in pediatric kidney transplant recipients a multicenter midwest pediatric nephrology consortium study
    Pediatric Transplantation, 2017
    Co-Authors: Sarah J Kizilbash, Ashton Chen, Katherine Twombley, Raed Bou Matar, Donna J Claes, Isa F Ashoor, Sara Jandeska, Jason M Misurac, Joseph R. Sherbotie, Priya S Verghese
    Abstract:

    Antibody-Mediated Rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of Antibody-Mediated Rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven Antibody-Mediated Rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for Antibody-Mediated Rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific Antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with Antibody-Mediated Rejection.

  • Bortezomib in the treatment of Antibody‐Mediated Rejection in pediatric kidney transplant recipients: A multicenter Midwest Pediatric Nephrology Consortium study
    Pediatric Transplantation, 2017
    Co-Authors: Sarah J Kizilbash, Ashton Chen, Katherine Twombley, Raed Bou Matar, Donna J Claes, Isa F Ashoor, Sara Jandeska, Jason M Misurac, Joseph R. Sherbotie, Priya S Verghese
    Abstract:

    Antibody-Mediated Rejection leads to allograft loss after kidney transplantation. Bortezomib has been used in adults for the reversal of Antibody-Mediated Rejection; however, pediatric data are limited. This retrospective study was conducted in collaboration with the Midwest Pediatric Nephrology Consortium. Pediatric kidney transplant recipients who received bortezomib for biopsy-proven Antibody-Mediated Rejection between 2008 and 2015 were included. The objective was to characterize the use of bortezomib in pediatric kidney transplant recipients. Thirty-three patients received bortezomib for Antibody-Mediated Rejection at nine pediatric kidney transplant centers. Ninety percent of patients received intravenous immunoglobulin, 78% received plasmapheresis, and 78% received rituximab. After a median follow-up of 15 months, 65% of patients had a functioning graft. The estimated glomerular filtration rate improved or stabilized in 61% and 36% of patients at 3 and 12 months post-bortezomib, respectively. The estimated glomerular filtration rate at diagnosis significantly predicted estimated glomerular filtration rate at 12 months after adjusting for chronic histologic changes (P .001). Fifty-six percent of patients showed an at least 25% reduction in the mean fluorescence intensity of the immune-dominant donor-specific Antibody, 1-3 months after the first dose of bortezomib. Non-life-threatening side effects were documented in 21 of 33 patients. Pediatric kidney transplant recipients tolerated bortezomib without life-threatening side effects. Bortezomib may stabilize estimated glomerular filtration rate for 3-6 months in pediatric kidney transplant recipients with Antibody-Mediated Rejection.

Kalathil K Sureshkumar - One of the best experts on this subject based on the ideXlab platform.

  • Treatment of Antibody-Mediated Rejection in kidney transplant recipients: a single-center experience with a bortezomib-based regimen.
    Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation, 2012
    Co-Authors: Janice G. Nigos, Swati Arora, Parineesha Nath, Sabiha M Hussain, Richard J. Marcus, Kalathil K Sureshkumar
    Abstract:

    OBJECTIVES Antibody-Mediated Rejection after kidney transplant is less responsive to conventional antiRejection therapies. The proteasome inhibitor bortezomib has activity against mature plasma cells that produce damaging donor-specific antibodies. We present our experience of using a bortezomib-based regimen in patients with severe Antibody-Mediated Rejection. MATERIALS AND METHODS A retrospective chart review was performed on patients with biopsy-proven Antibody-Mediated Rejection after kidney transplant at our institution over 12 months. Diagnosis of Antibody-Mediated Rejection was made on the basis of positive peritubular capillary C4d staining along with either histologic evidence of acute Rejection or positive donor-specific Antibody titers. Treatment for Antibody-Mediated Rejection included plasmapheresis, intravenous immunoglobulin, steroids, single-dose rituximab (375 mg/m²) along with bortezomib (1.3 mg/m²) on days 1, 4, 8, and 11. Antibody-Mediated Rejection was diagnosed in 6 patients. Patients received induction with either alemtuzumab (n=4) or rabbit-antithymocyte globulin (n=2) and were maintained on a tacrolimus/mycophenolate mofetil/early steroid withdrawal protocol. RESULTS Four of 6 patients responded to treatment. Patients had stable kidney function during followup (median 14 months) after bortezomib therapy. CONCLUSIONS In this series, we demonstrated the effectiveness of a bortezomib-based treatment regimen in achieving reduction of donor-specific Antibody titers and stable renal function in patients experiencing severe Antibody-Mediated Rejection.

  • Antibody-Mediated Rejection following renal transplantation
    Expert opinion on pharmacotherapy, 2007
    Co-Authors: Kalathil K Sureshkumar, Sabiha M Hussain, Barbara J Carpenter, Stephen Sandroni, Richard J. Marcus
    Abstract:

    Antibody-Mediated Rejection (AMR) accounts for 20 – 30% of all acute Rejection episodes following renal transplantation. AMR is generally less responsive to conventional anti-Rejection therapy, resulting in poor allograft survival. Introduction of C4d immunostaining of renal allograft biopsies and the demonstration of donor-specific antibodies in the recipients have increased our ability to diagnose AMR. Therapeutic options are evolving and include plasmapheresis, intravenous immunoglobulin, immunoadsorption and rituximab, together with intensification of immunosuppression with a tacrolimus/mycophenolate mofetil combination. Future studies might further define optimal therapeutic approach in renal transplant recipients presenting with AMR.

David N. Rush - One of the best experts on this subject based on the ideXlab platform.