The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Hiroshi Yagi - One of the best experts on this subject based on the ideXlab platform.
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successful living donor liver retransplantation for graft failure within 7 days due to acute de novo donor specific anti human leukocyte antigen antibody mediated rejection
Hepatology Research, 2018Co-Authors: Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Hiroshi YagiAbstract:Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
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a successful living donor liver re transplantation for graft failure within seven days due to acute de novo donor specific anti hla antibody mediated rejection
Hepatology Research, 2017Co-Authors: Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Hiroshi YagiAbstract:Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity (MFI) against HLA-DR15, which was possessed by both the first and the second donor, peaked at 12945 on the day before the second LTx. Anti-thymocyte globulin, plasma exchange along with intravenous immunoglobulin, rituximab and the local infusion of prostaglandin E1, steroids and mesilate gabexiate via portal catheter were provided to save the second graft. To our knowledge, this is the first report to demonstrate a clear association between de novo DSA and acute AMR within seven days after a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted-HLA. The rapid decision to carry out re-transplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
Henry F Mcfarland - One of the best experts on this subject based on the ideXlab platform.
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t cell recognition of myelin proteolipid protein and myelin proteolipid protein peptides in the peripheral blood of multiple sclerosis and control subjects
Journal of Neuroimmunology, 1998Co-Authors: John L Trotter, Clara M Pelfrey, Amy L Trotter, Jacqueline A Selvidge, Kelly C Gushleff, T Mohanakumar, Henry F McfarlandAbstract:Myelin proteolipid protein (PLP) is a prime candidate autoantigen for multiple sclerosis. In order to define potential immunodominant epitopes, T cell lines (TCL) from the peripheral blood of HLA-DR 15(2) MS patients were established which responded to the intact molecule of PLP. These TCL were then tested in individual proliferation assays with a variety of PLP peptides spanning most of the PLP molecule. Multiple peptides were recognized by TCL from the MS population, with more than one peptide often recognized by lines from the same individual. Three immunodominant peptides were identified which were recognized by the majority of MS patients. Estimated frequency analyses were then performed on the peripheral blood of HLA-DR15(2)-positive MS and control subjects using TCL initiated by the three immunodominant peptides, 40-60, 95-117, and 185-206. TCL from HLA-DR15 MS subjects recognized peptide 95-117 significantly more often than TCL from control subjects.
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t cell response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:Abstract In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DRα paired with the β chain encoded by DRB5*0101) and DR2b (DRα paired with the β chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131–159) are uniquely restricted by DR2a. The immunodominant middle epitope (81–99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
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t cell response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
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immunodominance of a low affinity major histocompatibility complex binding myelin basic protein epitope residues 111 129 in hla dr4 b1 0401 subjects is associated with a restricted t cell receptor repertoire
Journal of Clinical Investigation, 1997Co-Authors: Paolo A Muraro, Gerald T. Nepom, Henry F Mcfarland, M Kalbus, L R Tranquill, M Vergelli, Darhlene E Banks, James W Nagle, William E Biddison, Roland MartinAbstract:The pathogenesis of multiple sclerosis (MS) is currently ascribed in part to a T cell-mediated process targeting myelin components. The T cell response to one candidate autoantigen, myelin basic protein (MBP), in the context of HLA-DR15Dw2, has been previously studied in detail. However, the characteristics of cellular immunity in the context of other MS-associated HLA-DR haplotypes are scarcely known. MBP-specific T cell lines (TCL) were generated from HLA-DR4 (B1*0401)-positive MS subjects. Out of 275 MBP-specific TCL, 178 (64. 7%) specifically recognized region MBP(111-129), predominantly in the context of DRB1*0401. The major T cell epitope for MBP recognition corresponded to residues MBP(116-123). These TCL expressed disparate profiles of cytokine secretion and cytotoxicity. T cell receptor analysis, on the other hand, revealed a strikingly limited heterogeneity of rearrangements. In contrast to MBP(81-99), which binds with high affinity to HLA-DR15 and is recognized by a diverse T cell repertoire, MBP(111-129) binds weakly to DRB1*0401, suggesting that only high affinity T cell receptors might be able to efficiently engage such unstable MHC/peptide complexes, thus accounting for the T cell receptor restriction we observed. This study provides new insight about MBP recognition and proposes an alternative mechanism for immunodominance of self-antigen T cell epitopes in humans.
Eric O Long - One of the best experts on this subject based on the ideXlab platform.
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t cell response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:Abstract In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DRα paired with the β chain encoded by DRB5*0101) and DR2b (DRα paired with the β chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131–159) are uniquely restricted by DR2a. The immunodominant middle epitope (81–99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
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t cell response to myelin basic protein in the context of the multiple sclerosis associated hla dr15 haplotype peptide binding immunodominance and effector functions of t cells
Journal of Neuroimmunology, 1997Co-Authors: M Vergelli, Henry F Mcfarland, M Kalbus, S C Rojo, Bernhard Hemmer, Hubert Kalbacher, L R Tranquill, Hermann Beck, R De Mars, Eric O LongAbstract:In this study, we evaluated the role of the two functional HLA-DR heterodimers, DR2a (DR alpha paired with the beta chain encoded by DRB5*0101) and DR2b (DR alpha paired with the beta chain encoded by DRB1*1501), that are coexpressed in the multiple sclerosis (MS)-associated haplotype HLA-DR15 Dw2, in presenting myelin basic protein (MBP) peptides to MBP-specific T cell lines (TCL). Our results show that both HLA-DR molecules serve as restriction elements for HLA-DR15-restricted TCL. Slightly higher numbers of TCL use DR2a as restriction element, and the epitopes contained in the immunodominant C-terminal region (131-159) are uniquely restricted by DR2a. The immunodominant middle epitope (81-99) is recognized in the context of both DR2a and DR2b, but this specificity strongly dominates the DR2b-restricted T cell response. Overall, immunodominance in the MBP-specific T cell response correlated well with peptide binding to DR2a or DR2b, demonstrating that the affinity of MHC-peptide interactions is important for shaping the T cell response to this autoantigen. Furthermore, we show that binding of the middle MBP peptide to HLA-DR15 molecules prevents cleavage by cathepsin D, a protease abundantly found in endosomal processing compartments, and thus contributes to its immunodominance. Surprisingly, the restriction element employed by MBP-specific T cell clones influenced the effector function (i.e., cytotoxic activity) of T cells irrespective of their peptide fine specificity.
Yohei Yamada - One of the best experts on this subject based on the ideXlab platform.
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successful living donor liver retransplantation for graft failure within 7 days due to acute de novo donor specific anti human leukocyte antigen antibody mediated rejection
Hepatology Research, 2018Co-Authors: Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Hiroshi YagiAbstract:Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a 3-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity against human leukocyte antigen (HLA)-DR15, which was possessed by both the first and the second donor, peaked at 12 945 on the day before the second LTx. Antithymocyte globulin, plasma exchange along with i.v. immunoglobulin, rituximab, and the local infusion of prostaglandin E1, steroids, and Mesilate gabexate through a portal catheter were provided to save the second graft. To our knowledge, this is the first report to show a clear association between de novo DSA and acute AMR within 7 days of a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted HLA. The rapid decision to carry out retransplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
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a successful living donor liver re transplantation for graft failure within seven days due to acute de novo donor specific anti hla antibody mediated rejection
Hepatology Research, 2017Co-Authors: Yohei Yamada, Ken Hoshino, Teisaburo Mori, Miho Kawaida, Hideo Ishihama, Takahiro Shimizu, Nobuhiro Takahashi, Kentaro Matsubara, Taizo Hibi, Hiroshi YagiAbstract:Growing evidence suggests a relationship between antibody-mediated rejection (AMR) and early graft failure due to a previously unknown etiology in liver transplantation (LTx). We herein report a three-year-old boy who developed rapid graft failure due to de novo donor-specific antibody (DSA)-driven AMR a week after living donor LTx, requiring a second transplant on the 10th day after the first LTx. The pathology of the first graft showed massive necrosis in zone 3 along with positive C4d and inflammatory cell infiltrates in portal areas. The mean fluorescence intensity (MFI) against HLA-DR15, which was possessed by both the first and the second donor, peaked at 12945 on the day before the second LTx. Anti-thymocyte globulin, plasma exchange along with intravenous immunoglobulin, rituximab and the local infusion of prostaglandin E1, steroids and mesilate gabexiate via portal catheter were provided to save the second graft. To our knowledge, this is the first report to demonstrate a clear association between de novo DSA and acute AMR within seven days after a LTx. Furthermore, we successfully rescued the recipient with a second graft despite possessing the same targeted-HLA. The rapid decision to carry out re-transplantation and specific strategies overcoming AMR were crucial to achieving success in this case of immunologically high-risk LTx.
Mitchell S Cairo - One of the best experts on this subject based on the ideXlab platform.
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hla dr15 antigen status does not impact graft versus host disease or survival in hla matched sibling transplantation for hematologic malignancies
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Minoo Battiwalla, Kristin Ellis, Steven Z Pavletic, Gorgun Akpek, Peiman Hematti, Thomas R Klumpp, Richard T Maziarz, Bipin N Savani, Mahmoud Aljurf, Mitchell S CairoAbstract:The HLA class II DRB1 antigen DR15 is an important prognostic marker in immune-mediated marrow failure states. DR15 has also been associated with favorable outcomes (reduced acute graft-versus-host disease [aGVHD] and relapse) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on transplantation outcomes, we conducted a retrospective study of 2891 recipients of first allogeneic stem cell transplant from HLA-matched sibling donors for the treatment of acute leukemia, chronic myeloid leukemia, or myelodysplastic syndrome (MDS) between 1990 and 2007. All patients received conventional myeloablative conditioning, T-replete grafts, and cyclosporine plus methotrexate-based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 patients (25.3%) as positive and 2159 patients (74.7%) as negative for DRB1*15:01 or *15:02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15 positive and negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, aGVHD, chronic GVHD (cGVHD), treatment-related mortality, relapse, disease-free survival, or overall survival (OS). In multivariate analysis, DR15 status showed no significant difference in aGVHD, cGVHD, OS, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplant outcomes in this large and homogenous cohort of patients with leukemia and MDS.
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hla dr15 antigen status does not impact graft versus host disease or disease free survival in hla matched sibling transplantation for hematologic malignancies
Blood, 2011Co-Authors: Minoo Battiwalla, Kristin Ellis, Steven Z Pavletic, Gorgun Akpek, Peiman Hematti, Thomas R Klumpp, Richard T Maziarz, Bipin N Savani, Mahmoud Aljurf, Mitchell S CairoAbstract:Abstract 3094 The HLA class II DRB1 antigen DR15 is an important immunobiologic marker in immune mediated marrow failure states. DR15 has also been reported in small studies to be associated with favorable outcomes (reduction in acute GVHD and reduced relapse resulting in improved overall survival) after allogeneic hematopoietic cell transplant. To elucidate the impact of DR15 on major transplant outcomes, we conducted a retrospective study of 2, 891 recipients of first marrow or mobilized peripheral blood stem cell transplantation for the treatment of acute myeloid leukemia (n=1038), acute lymphoblastic leukemia (n=700), chronic myeloid leukemia (n=948), or myelodysplastic syndrome (n=205) between 1990–2008 and reported to the CIBMTR registry. Selection was confined to HLA-identical sibling transplantation to avoid HLA-disparity as a driving force for observed differences. All patients received conventional myeloablative conditioning, T-replete grafts and cyclosporine plus methotrexate- based GVHD prophylaxis. DNA-based HLA typing allowed categorization of 732 (25.3%) patients as positive and 2159 (74.7%) patients as negative for DRB1*15 :01 or *15 :02 (DR15). There were no significant differences in baseline characteristics between the HLA DR15-positive and -negative groups. In univariate analysis, HLA-DR15 status had no impact on neutrophil engraftment, acute graft-versus-host disease (GvHD) II-IV or III-IV, chronic GVHD, treatment related mortality, relapse, disease-free survival or overall survival. Confining the univariate analysis to myeloid malignancies did not alter these findings. Multivariate analysis models were constructed with DR15 status forced into the models in all steps of model building and the final model regardless of its statistical significance. Other variables tested included: donor/recipient age, CMV status, disease, disease stage, graft source, Karnofsky score, race and year of transplant. Variables that attained a p-value ≤0.05 were held in the final multivariate models. In multivariate analysis, DR15 status showed no significant difference in the primary outcomes of acute GVHD II-IV or III-IV, chronic GVHD, overall survival, or relapse. In conclusion, DR15 status had no impact on major HLA-matched sibling donor hematopoietic cell transplantation outcomes in this large and homogenous cohort of leukemia and MDS patients. Disclosures: No relevant conflicts of interest to declare.