Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab

Andrew L. Lobashevsky, Nancy G. Higgins, Kevin M. Rosner, Muhammad Mujtaba, William C. Goggins, Tim E. Taber

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

BACKGROUND: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. METHODS: In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. RESULTS: Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. CONCLUSIONS: The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Original languageEnglish (US)
Pages (from-to)182-190
Number of pages9
JournalTransplantation
Volume96
Issue number2
DOIs
StatePublished - Jul 27 2013
Externally publishedYes

Fingerprint

Intravenous Immunoglobulins
Anti-Idiotypic Antibodies
Transplants
Kidney
Antibodies
Immunoglobulin Isotypes
HLA Antigens
Rituximab
Fluorescence
Immunomodulation
Graft Rejection

Keywords

  • Antibodies
  • Desensitization
  • HLA
  • MFI
  • Rebound

ASJC Scopus subject areas

  • Transplantation

Cite this

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab. / Lobashevsky, Andrew L.; Higgins, Nancy G.; Rosner, Kevin M.; Mujtaba, Muhammad; Goggins, William C.; Taber, Tim E.

In: Transplantation, Vol. 96, No. 2, 27.07.2013, p. 182-190.

Research output: Contribution to journalArticle

Lobashevsky, Andrew L. ; Higgins, Nancy G. ; Rosner, Kevin M. ; Mujtaba, Muhammad ; Goggins, William C. ; Taber, Tim E. / Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab. In: Transplantation. 2013 ; Vol. 96, No. 2. pp. 182-190.
@article{b1af0c11286c4835abc0bcc12917ad48,
title = "Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab",
abstract = "BACKGROUND: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. METHODS: In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34{\%}-99{\%}), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. RESULTS: Reduction of cPRA from 25{\%} to 50{\%} was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50{\%} was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65{\%} patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. CONCLUSIONS: The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.",
keywords = "Antibodies, Desensitization, HLA, MFI, Rebound",
author = "Lobashevsky, {Andrew L.} and Higgins, {Nancy G.} and Rosner, {Kevin M.} and Muhammad Mujtaba and Goggins, {William C.} and Taber, {Tim E.}",
year = "2013",
month = "7",
day = "27",
doi = "10.1097/TP.0b013e3182962c84",
language = "English (US)",
volume = "96",
pages = "182--190",
journal = "Transplantation",
issn = "0041-1337",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab

AU - Lobashevsky, Andrew L.

AU - Higgins, Nancy G.

AU - Rosner, Kevin M.

AU - Mujtaba, Muhammad

AU - Goggins, William C.

AU - Taber, Tim E.

PY - 2013/7/27

Y1 - 2013/7/27

N2 - BACKGROUND: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. METHODS: In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. RESULTS: Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. CONCLUSIONS: The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

AB - BACKGROUND: Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. METHODS: In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%-99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti-human leukocyte antigen antibodies were analyzed before and after desensitization. RESULTS: Reduction of cPRA from 25% to 50% was noted for anti-class I (5 patients, within 20-60 days) and anti-class II (3 patients, within 10-20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti-class I antibodies at 350 days and anti-class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti-class II antibodies, and history of previous transplant. CONCLUSIONS: The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

KW - Antibodies

KW - Desensitization

KW - HLA

KW - MFI

KW - Rebound

UR - http://www.scopus.com/inward/record.url?scp=84880570903&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880570903&partnerID=8YFLogxK

U2 - 10.1097/TP.0b013e3182962c84

DO - 10.1097/TP.0b013e3182962c84

M3 - Article

VL - 96

SP - 182

EP - 190

JO - Transplantation

JF - Transplantation

SN - 0041-1337

IS - 2

ER -