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 Chen, Takehiko Dohi, Ashraf El-Hinnawi, Siegfredo Paloyo, Jeffrey J. Gaynor, Adela 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 (US)
Pages (from-to)88-92
Number of pages5
JournalTransplant Immunology
Volume30
Issue number2-3
DOIs
StatePublished - Jan 1 2014

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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

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

Sageshima, Junichiro ; Ciancio, Gaetano ; Chen, Linda ; Dohi, Takehiko ; El-Hinnawi, Ashraf ; Paloyo, Siegfredo ; Gaynor, Jeffrey J. ; Mattiazzi, Adela ; Guerra, Giselle ; Kupin, Warren ; Roth, David ; Ruiz, Phillip ; Burke, George W. / 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. In: Transplant Immunology. 2014 ; Vol. 30, No. 2-3. pp. 88-92.
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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.",
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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. / Sageshima, Junichiro; Ciancio, Gaetano; Chen, Linda; Dohi, Takehiko; El-Hinnawi, Ashraf; Paloyo, Siegfredo; Gaynor, Jeffrey J.; Mattiazzi, Adela; Guerra, Giselle; Kupin, Warren; Roth, David; Ruiz, Phillip; Burke, George W.

In: Transplant Immunology, Vol. 30, No. 2-3, 01.01.2014, p. 88-92.

Research output: Contribution to journalArticle

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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

AU - Dohi, Takehiko

AU - El-Hinnawi, Ashraf

AU - Paloyo, Siegfredo

AU - Gaynor, Jeffrey J.

AU - Mattiazzi, Adela

AU - Guerra, Giselle

AU - Kupin, Warren

AU - Roth, David

AU - Ruiz, Phillip

AU - Burke, George W.

PY - 2014/1/1

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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.

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