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Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation

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Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation. / Guthoff, Martina; Schmid-Horch, Barbara; Weisel, Katja C; Häring, Hans-Ulrich; Königsrainer, Alfred; Heyne, Nils.

in: TRANSPL IMMUNOL, Jahrgang 26, Nr. 4, 06.2012, S. 171-5.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Guthoff, M, Schmid-Horch, B, Weisel, KC, Häring, H-U, Königsrainer, A & Heyne, N 2012, 'Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation', TRANSPL IMMUNOL, Jg. 26, Nr. 4, S. 171-5. https://doi.org/10.1016/j.trim.2012.01.002

APA

Guthoff, M., Schmid-Horch, B., Weisel, K. C., Häring, H-U., Königsrainer, A., & Heyne, N. (2012). Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation. TRANSPL IMMUNOL, 26(4), 171-5. https://doi.org/10.1016/j.trim.2012.01.002

Vancouver

Guthoff M, Schmid-Horch B, Weisel KC, Häring H-U, Königsrainer A, Heyne N. Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation. TRANSPL IMMUNOL. 2012 Jun;26(4):171-5. https://doi.org/10.1016/j.trim.2012.01.002

Bibtex

@article{30577cc9f8224d27b3d4405f87fe21d2,
title = "Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation",
abstract = "BACKGROUND: Sensitization to human leukocyte antigen (HLA) prolongs waiting list time and reduces allograft survival in solid organ transplantation. Current strategies for pretransplant desensitization are based on B-cell depletion and extracorporeal treatment. The proteasome inhibitor bortezomib allows direct targeting of the antibody-producing plasma cell and has been used in antibody-mediated rejection (AMR) and recipient desensitization with varying results. Here, we report the effect of bortezomib preconditioning on HLA antibody titers and specificity in highly sensitized patients awaiting renal allograft transplantation.PATIENTS AND METHODS: Two highly sensitized patients awaiting third kidney transplantation were given one cycle of bortezomib (1.3 mg/m², days 1, 4, 8, 11), as part of recipient desensitization. Time-course and levels of anti-HLA antibodies, as well as specificity to previous transplant antigens were monitored by luminex technology. In addition, measles and tetanus toxoid immunoglobulin G (IgG) was measured.RESULTS: Following bortezomib, overall changes in IgG levels were small and no sustained reduction in anti-HLA class I or II antibody levels was observed over more than 100 days of follow-up to both, donor specific and non-donor specific antigens. Moreover, anti-measles and -tetanus toxoid IgG levels remained unchanged.CONCLUSIONS: Bortezomib preconditioning alone does not result in sustained reduction of HLA antibody levels or alter protective immunity in sensitized patients. This supports the notion, that bortezomib requires activation of plasma cells, as in AMR, to effectively reduce HLA antibody production. Hence, in a pretransplant setting, combination strategies may be required to derive benefit from proteasome inhibition.",
keywords = "Boronic Acids, Bortezomib, Epitopes, Female, Follow-Up Studies, Graft Rejection, HLA Antigens, Humans, Immunity, Humoral, Immunization, Immunoglobulin G, Kidney Transplantation, Lymphocyte Activation, Male, Plasma Cells, Proteasome Inhibitors, Pyrazines, Reoperation, Transplantation Conditioning, Journal Article",
author = "Martina Guthoff and Barbara Schmid-Horch and Weisel, {Katja C} and Hans-Ulrich H{\"a}ring and Alfred K{\"o}nigsrainer and Nils Heyne",
note = "Copyright {\textcopyright} 2012 Elsevier B.V. All rights reserved.",
year = "2012",
month = jun,
doi = "10.1016/j.trim.2012.01.002",
language = "English",
volume = "26",
pages = "171--5",
journal = "TRANSPL IMMUNOL",
issn = "0966-3274",
publisher = "Elsevier",
number = "4",

}

RIS

TY - JOUR

T1 - Proteasome inhibition by bortezomib: effect on HLA-antibody levels and specificity in sensitized patients awaiting renal allograft transplantation

AU - Guthoff, Martina

AU - Schmid-Horch, Barbara

AU - Weisel, Katja C

AU - Häring, Hans-Ulrich

AU - Königsrainer, Alfred

AU - Heyne, Nils

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/6

Y1 - 2012/6

N2 - BACKGROUND: Sensitization to human leukocyte antigen (HLA) prolongs waiting list time and reduces allograft survival in solid organ transplantation. Current strategies for pretransplant desensitization are based on B-cell depletion and extracorporeal treatment. The proteasome inhibitor bortezomib allows direct targeting of the antibody-producing plasma cell and has been used in antibody-mediated rejection (AMR) and recipient desensitization with varying results. Here, we report the effect of bortezomib preconditioning on HLA antibody titers and specificity in highly sensitized patients awaiting renal allograft transplantation.PATIENTS AND METHODS: Two highly sensitized patients awaiting third kidney transplantation were given one cycle of bortezomib (1.3 mg/m², days 1, 4, 8, 11), as part of recipient desensitization. Time-course and levels of anti-HLA antibodies, as well as specificity to previous transplant antigens were monitored by luminex technology. In addition, measles and tetanus toxoid immunoglobulin G (IgG) was measured.RESULTS: Following bortezomib, overall changes in IgG levels were small and no sustained reduction in anti-HLA class I or II antibody levels was observed over more than 100 days of follow-up to both, donor specific and non-donor specific antigens. Moreover, anti-measles and -tetanus toxoid IgG levels remained unchanged.CONCLUSIONS: Bortezomib preconditioning alone does not result in sustained reduction of HLA antibody levels or alter protective immunity in sensitized patients. This supports the notion, that bortezomib requires activation of plasma cells, as in AMR, to effectively reduce HLA antibody production. Hence, in a pretransplant setting, combination strategies may be required to derive benefit from proteasome inhibition.

AB - BACKGROUND: Sensitization to human leukocyte antigen (HLA) prolongs waiting list time and reduces allograft survival in solid organ transplantation. Current strategies for pretransplant desensitization are based on B-cell depletion and extracorporeal treatment. The proteasome inhibitor bortezomib allows direct targeting of the antibody-producing plasma cell and has been used in antibody-mediated rejection (AMR) and recipient desensitization with varying results. Here, we report the effect of bortezomib preconditioning on HLA antibody titers and specificity in highly sensitized patients awaiting renal allograft transplantation.PATIENTS AND METHODS: Two highly sensitized patients awaiting third kidney transplantation were given one cycle of bortezomib (1.3 mg/m², days 1, 4, 8, 11), as part of recipient desensitization. Time-course and levels of anti-HLA antibodies, as well as specificity to previous transplant antigens were monitored by luminex technology. In addition, measles and tetanus toxoid immunoglobulin G (IgG) was measured.RESULTS: Following bortezomib, overall changes in IgG levels were small and no sustained reduction in anti-HLA class I or II antibody levels was observed over more than 100 days of follow-up to both, donor specific and non-donor specific antigens. Moreover, anti-measles and -tetanus toxoid IgG levels remained unchanged.CONCLUSIONS: Bortezomib preconditioning alone does not result in sustained reduction of HLA antibody levels or alter protective immunity in sensitized patients. This supports the notion, that bortezomib requires activation of plasma cells, as in AMR, to effectively reduce HLA antibody production. Hence, in a pretransplant setting, combination strategies may be required to derive benefit from proteasome inhibition.

KW - Boronic Acids

KW - Bortezomib

KW - Epitopes

KW - Female

KW - Follow-Up Studies

KW - Graft Rejection

KW - HLA Antigens

KW - Humans

KW - Immunity, Humoral

KW - Immunization

KW - Immunoglobulin G

KW - Kidney Transplantation

KW - Lymphocyte Activation

KW - Male

KW - Plasma Cells

KW - Proteasome Inhibitors

KW - Pyrazines

KW - Reoperation

KW - Transplantation Conditioning

KW - Journal Article

U2 - 10.1016/j.trim.2012.01.002

DO - 10.1016/j.trim.2012.01.002

M3 - SCORING: Journal article

C2 - 22326708

VL - 26

SP - 171

EP - 175

JO - TRANSPL IMMUNOL

JF - TRANSPL IMMUNOL

SN - 0966-3274

IS - 4

ER -