A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation

Annette Jackson, Edward Kraus, Babak J. Orandi, Dorry Segev, Robert A. Montgomery, Andrea A. Zachary

Research output: Contribution to journalArticle

Abstract

Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32% DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab-treated patients, of the 39 HLA antibodies that increased post transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B-cell depletion. Compared with controls, rituximab-treated patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab treated-and 40% in non-treated recipients). Thus, rituximab induction in HLA-incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5-year allograft survival when compared with recipients desensitized and transplanted without rituximab.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalKidney International
Volume87
Issue number2
DOIs
StatePublished - Feb 3 2015

Fingerprint

HLA Antigens
Kidney Transplantation
Antibodies
Tissue Donors
Allografts
Rituximab
B-Lymphocytes
Transplants
Fluorescence
Pregnancy

Keywords

  • B cells
  • desensitization
  • HLA antibody
  • kidney transplantation
  • rituximab

ASJC Scopus subject areas

  • Nephrology

Cite this

A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation. / Jackson, Annette; Kraus, Edward; Orandi, Babak J.; Segev, Dorry; Montgomery, Robert A.; Zachary, Andrea A.

In: Kidney International, Vol. 87, No. 2, 03.02.2015, p. 409-416.

Research output: Contribution to journalArticle

Jackson, Annette ; Kraus, Edward ; Orandi, Babak J. ; Segev, Dorry ; Montgomery, Robert A. ; Zachary, Andrea A. / A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation. In: Kidney International. 2015 ; Vol. 87, No. 2. pp. 409-416.
@article{6f6ad454b061413092aa0aaa79f89a90,
title = "A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation",
abstract = "Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7{\%} of donor-specific antibodies (DSAs) and 33{\%} of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32{\%} DSAs and 55{\%} non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab-treated patients, of the 39 HLA antibodies that increased post transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B-cell depletion. Compared with controls, rituximab-treated patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean fluorescence intensity), but a similar rate of DSA persistence (52{\%} in rituximab treated-and 40{\%} in non-treated recipients). Thus, rituximab induction in HLA-incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5-year allograft survival when compared with recipients desensitized and transplanted without rituximab.",
keywords = "B cells, desensitization, HLA antibody, kidney transplantation, rituximab",
author = "Annette Jackson and Edward Kraus and Orandi, {Babak J.} and Dorry Segev and Montgomery, {Robert A.} and Zachary, {Andrea A.}",
year = "2015",
month = "2",
day = "3",
doi = "10.1038/ki.2014.261",
language = "English (US)",
volume = "87",
pages = "409--416",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - A closer look at rituximab induction on HLA antibody rebound following HLA-incompatible kidney transplantation

AU - Jackson, Annette

AU - Kraus, Edward

AU - Orandi, Babak J.

AU - Segev, Dorry

AU - Montgomery, Robert A.

AU - Zachary, Andrea A.

PY - 2015/2/3

Y1 - 2015/2/3

N2 - Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32% DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab-treated patients, of the 39 HLA antibodies that increased post transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B-cell depletion. Compared with controls, rituximab-treated patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab treated-and 40% in non-treated recipients). Thus, rituximab induction in HLA-incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5-year allograft survival when compared with recipients desensitized and transplanted without rituximab.

AB - Rituximab has been used to increase the efficacy of desensitization protocols for human leukocyte antigen (HLA)-incompatible kidney transplantation; however, controlled comparisons have not been reported. Here we examined 256 post-transplant HLA antibody levels in 25 recipients desensitized with and 25 without rituximab induction, to determine the impact of B-cell depletion. We found significantly less HLA antibody rebound in the rituximab-treated patients (7% of donor-specific antibodies (DSAs) and 33% of non-DSAs) compared with a control cohort desensitized and transplanted without rituximab (32% DSAs and 55% non-DSAs). The magnitude of the increase was significantly larger among patients who did not receive rituximab. Interestingly, in rituximab-treated patients, of the 39 HLA antibodies that increased post transplant, 34 were specific for HLA mismatches present in previous allografts or pregnancies, implying limited efficacy in memory B-cell depletion. Compared with controls, rituximab-treated patients had a significantly greater mean reduction in DSA (-2505 vs. -292 mean fluorescence intensity), but a similar rate of DSA persistence (52% in rituximab treated-and 40% in non-treated recipients). Thus, rituximab induction in HLA-incompatible recipients reduced the incidence and magnitude of HLA antibody rebound, but did not affect DSA elimination, antibody-mediated rejection, or 5-year allograft survival when compared with recipients desensitized and transplanted without rituximab.

KW - B cells

KW - desensitization

KW - HLA antibody

KW - kidney transplantation

KW - rituximab

UR - http://www.scopus.com/inward/record.url?scp=84922171483&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84922171483&partnerID=8YFLogxK

U2 - 10.1038/ki.2014.261

DO - 10.1038/ki.2014.261

M3 - Article

C2 - 25054778

AN - SCOPUS:84922171483

VL - 87

SP - 409

EP - 416

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 2

ER -