Lack of clinical association and effect of peripheral WBC counts on immune cell function test in kidney transplant recipients with T-cell depleting induction and steroid-sparing maintenance therapy

Junichiro Sageshima, Gaetano Ciancio, Linda J Chen, Takehiko Dohi, Ashraf El-Hinnawi, Siegfredo Paloyo, Jeffrey Gaynor, Adela D Mattiazzi, Giselle Guerra, Warren Kupin, David Roth, Phillip Ruiz, George W Burke

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The Cylex ImmuKnow assay measures the amount of stimulated ATP production by CD4+ T-cells, and has been used clinically, trying to predict rejection and infection episodes. However, predictive values of this assay after induction therapy with steroid-sparing maintenance protocols are unclear. In this single-center cohort study, we analyzed renal transplant recipients who received T-cell depleting+/-anti-IL2 receptor antibodies and tacrolimus/mycophenolate maintenance without steroids. A total of 4224 ImmuKnow levels in 306 patients were available for analysis. ImmuKnow levels (Mean±SE) changed over time after induction therapy with a paradoxical initial increase: 419±23, 461±32, 519±14, 411±10, 344±6, and 405±3 for pre-transplant, 0-1wk, 1wk-1mo, 1-3mos, 3mos-1yr, and thereafter. This change was parallel to the evolution of peripheral WBC counts and ImmuKnow levels had weak but significant correlation with WBC counts (R2=0.264, P<0.0001). The levels for biopsy-proven rejection (389±56) and borderline/clinical rejection (254±41) were not significantly higher than the levels of quiescent patients. The levels for opportunistic infection (349±48) and other infections (345±27) were not significantly lower than the levels of quiescent patients. The longitudinal changes in ImmuKnow levels were not predictive of rejection or infection. In conclusion, ImmuKnow levels can vary after T-cell depleting induction therapies at various time points, even without significant clinical events. Since ImmuKnow levels seem to be affected by WBC counts, ImmuKnow results need to be interpreted with caution. The effects of leukocytosis or leukopenia caused by immunosuppressive medication on the ImmuKnow assay need further investigation.

Original languageEnglish
Pages (from-to)88-92
Number of pages5
JournalTransplant Immunology
Volume30
Issue number2-3
DOIs
StatePublished - Jan 1 2014

Fingerprint

Kidney Function Tests
Steroids
T-Lymphocytes
Infection
Maintenance
Interleukin-2 Receptors
Leukocytosis
Opportunistic Infections
Leukopenia
Tacrolimus
Immunosuppressive Agents
Cohort Studies
Therapeutics
Adenosine Triphosphate
Transplants
Kidney
Biopsy
Antibodies
Transplant Recipients

Keywords

  • Antibody therapy
  • Cylex
  • ImmuKnow
  • Infection
  • Kidney transplant
  • Rejection

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Transplantation

Cite this

@article{88900961f9ef4ee7ababdfc9d8584776,
title = "Lack of clinical association and effect of peripheral WBC counts on immune cell function test in kidney transplant recipients with T-cell depleting induction and steroid-sparing maintenance therapy",
abstract = "The Cylex ImmuKnow assay measures the amount of stimulated ATP production by CD4+ T-cells, and has been used clinically, trying to predict rejection and infection episodes. However, predictive values of this assay after induction therapy with steroid-sparing maintenance protocols are unclear. In this single-center cohort study, we analyzed renal transplant recipients who received T-cell depleting+/-anti-IL2 receptor antibodies and tacrolimus/mycophenolate maintenance without steroids. A total of 4224 ImmuKnow levels in 306 patients were available for analysis. ImmuKnow levels (Mean±SE) changed over time after induction therapy with a paradoxical initial increase: 419±23, 461±32, 519±14, 411±10, 344±6, and 405±3 for pre-transplant, 0-1wk, 1wk-1mo, 1-3mos, 3mos-1yr, and thereafter. This change was parallel to the evolution of peripheral WBC counts and ImmuKnow levels had weak but significant correlation with WBC counts (R2=0.264, P<0.0001). The levels for biopsy-proven rejection (389±56) and borderline/clinical rejection (254±41) were not significantly higher than the levels of quiescent patients. The levels for opportunistic infection (349±48) and other infections (345±27) were not significantly lower than the levels of quiescent patients. The longitudinal changes in ImmuKnow levels were not predictive of rejection or infection. In conclusion, ImmuKnow levels can vary after T-cell depleting induction therapies at various time points, even without significant clinical events. Since ImmuKnow levels seem to be affected by WBC counts, ImmuKnow results need to be interpreted with caution. The effects of leukocytosis or leukopenia caused by immunosuppressive medication on the ImmuKnow assay need further investigation.",
keywords = "Antibody therapy, Cylex, ImmuKnow, Infection, Kidney transplant, Rejection",
author = "Junichiro Sageshima and Gaetano Ciancio and Chen, {Linda J} and Takehiko Dohi and Ashraf El-Hinnawi and Siegfredo Paloyo and Jeffrey Gaynor and Mattiazzi, {Adela D} and Giselle Guerra and Warren Kupin and David Roth and Phillip Ruiz and Burke, {George W}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.trim.2014.01.003",
language = "English",
volume = "30",
pages = "88--92",
journal = "Transplant Immunology",
issn = "0966-3274",
publisher = "Elsevier",
number = "2-3",

}

TY - JOUR

T1 - Lack of clinical association and effect of peripheral WBC counts on immune cell function test in kidney transplant recipients with T-cell depleting induction and steroid-sparing maintenance therapy

AU - Sageshima, Junichiro

AU - Ciancio, Gaetano

AU - Chen, Linda J

AU - Dohi, Takehiko

AU - El-Hinnawi, Ashraf

AU - Paloyo, Siegfredo

AU - Gaynor, Jeffrey

AU - Mattiazzi, Adela D

AU - Guerra, Giselle

AU - Kupin, Warren

AU - Roth, David

AU - Ruiz, Phillip

AU - Burke, George W

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The Cylex ImmuKnow assay measures the amount of stimulated ATP production by CD4+ T-cells, and has been used clinically, trying to predict rejection and infection episodes. However, predictive values of this assay after induction therapy with steroid-sparing maintenance protocols are unclear. In this single-center cohort study, we analyzed renal transplant recipients who received T-cell depleting+/-anti-IL2 receptor antibodies and tacrolimus/mycophenolate maintenance without steroids. A total of 4224 ImmuKnow levels in 306 patients were available for analysis. ImmuKnow levels (Mean±SE) changed over time after induction therapy with a paradoxical initial increase: 419±23, 461±32, 519±14, 411±10, 344±6, and 405±3 for pre-transplant, 0-1wk, 1wk-1mo, 1-3mos, 3mos-1yr, and thereafter. This change was parallel to the evolution of peripheral WBC counts and ImmuKnow levels had weak but significant correlation with WBC counts (R2=0.264, P<0.0001). The levels for biopsy-proven rejection (389±56) and borderline/clinical rejection (254±41) were not significantly higher than the levels of quiescent patients. The levels for opportunistic infection (349±48) and other infections (345±27) were not significantly lower than the levels of quiescent patients. The longitudinal changes in ImmuKnow levels were not predictive of rejection or infection. In conclusion, ImmuKnow levels can vary after T-cell depleting induction therapies at various time points, even without significant clinical events. Since ImmuKnow levels seem to be affected by WBC counts, ImmuKnow results need to be interpreted with caution. The effects of leukocytosis or leukopenia caused by immunosuppressive medication on the ImmuKnow assay need further investigation.

AB - The Cylex ImmuKnow assay measures the amount of stimulated ATP production by CD4+ T-cells, and has been used clinically, trying to predict rejection and infection episodes. However, predictive values of this assay after induction therapy with steroid-sparing maintenance protocols are unclear. In this single-center cohort study, we analyzed renal transplant recipients who received T-cell depleting+/-anti-IL2 receptor antibodies and tacrolimus/mycophenolate maintenance without steroids. A total of 4224 ImmuKnow levels in 306 patients were available for analysis. ImmuKnow levels (Mean±SE) changed over time after induction therapy with a paradoxical initial increase: 419±23, 461±32, 519±14, 411±10, 344±6, and 405±3 for pre-transplant, 0-1wk, 1wk-1mo, 1-3mos, 3mos-1yr, and thereafter. This change was parallel to the evolution of peripheral WBC counts and ImmuKnow levels had weak but significant correlation with WBC counts (R2=0.264, P<0.0001). The levels for biopsy-proven rejection (389±56) and borderline/clinical rejection (254±41) were not significantly higher than the levels of quiescent patients. The levels for opportunistic infection (349±48) and other infections (345±27) were not significantly lower than the levels of quiescent patients. The longitudinal changes in ImmuKnow levels were not predictive of rejection or infection. In conclusion, ImmuKnow levels can vary after T-cell depleting induction therapies at various time points, even without significant clinical events. Since ImmuKnow levels seem to be affected by WBC counts, ImmuKnow results need to be interpreted with caution. The effects of leukocytosis or leukopenia caused by immunosuppressive medication on the ImmuKnow assay need further investigation.

KW - Antibody therapy

KW - Cylex

KW - ImmuKnow

KW - Infection

KW - Kidney transplant

KW - Rejection

UR - http://www.scopus.com/inward/record.url?scp=84896549851&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896549851&partnerID=8YFLogxK

U2 - 10.1016/j.trim.2014.01.003

DO - 10.1016/j.trim.2014.01.003

M3 - Article

C2 - 24518158

AN - SCOPUS:84896549851

VL - 30

SP - 88

EP - 92

JO - Transplant Immunology

JF - Transplant Immunology

SN - 0966-3274

IS - 2-3

ER -