Elsevier

Transplantation Proceedings

Volume 42, Issue 7, September 2010, Pages 2567-2571
Transplantation Proceedings

Liver transplantation
Candidate
Peritransplant Monitoring of Immune Cell Function in Adult Living Donor Liver Transplantation

https://doi.org/10.1016/j.transproceed.2010.04.040Get rights and content

Abstract

Purpose

We evaluated the clinical utility of peritransplant in vitro assays of immune cell function in adult living donor liver transplant (LDLT) recipients.

Methods

In particular, we measured immune cell function, using the ImmuKnow assay, in 107 adult LDLT recipients and 200 potential living liver donors (control group) admitted to our center between July 2008 and January 2009.

Results

In the control group, the mean proportion of T-helper/inducer cells was 36.8% ± 8.2%. The degree of immune response was strong in 12%, moderate in 77%, and low in 11%. In the study group, the degree of immune response within the first month was strong in 4.6%, moderate in 38.2%, and low in 57.2%, thus significantly lower than in the control group (P < .001). ImmuKnow results and tacrolimus levels did not show a significant correlation (r2 = .002, P = .392). Although six patients showed biopsy-proven acute cellular rejection, none showed a strong immune response. Patients with overt infection showed a lower immune response.

Conclusions

These results indicate that peritransplant assessment of immune response using the ImmuKnow assay does not reliably predict the occurrence of acute rejection. Additional studies are necessary to accurately assess the clinical utility of immune response monitoring.

Section snippets

Patients and Methods

Between July 2008 and January 2009, 128 adult patients undergoing primary LDLT at our institution were prospectively enrolled. Blood samples were taken 1 day before OLT, twice during the first week after OLT, and once a week thereafter until discharge from the hospital. Patients readmitted for graft dysfunction were also included in our survey. Immune cell function was assayed by the ImmuKnow assay (Cylex Inc, Columbia, Md, USA). However, patients assayed by ImmuKnow fewer than three times

Immune Cell Function in Healthy Individuals

The 200 living donor candidates consisted of 133 men (66.5%) and 67 women (33.5%), of mean age 32.6 ± 9.1 years (range, 20–57 years). The mean proportion of T-helper/inducer cells was 36.8% ± 8.2% (range: 16.3%–59.9%). In response to ImmuKnow, 24 (12%) individuals showed a strong immune response, 154 (77%) a moderate response, and 22 (11%) a low response (Fig 1). There was no significant correlation between age and ImmuKnow level (r2 < .001, P = .08). However, men tended to show a stronger

Discussion

Monitoring of functional immunity in OLT recipients may help in appropriate management of such patients, avoiding acute rejection and the side effects of drugs and infections, especially during the early posttransplant period. As most serious complications following LDLT occur within the first few months, strict patient surveillance, including monitoring of rejection and infection, should be maintained for this period. The ImmuKnow assay is specifically designed to assess the overall immune

References (10)

  • P. Rovira et al.

    The impact of immune suppressive drugs on the analysis of T cell activation

    Curr Med Chem

    (2000)
  • R. Venkataraman et al.

    Clinical utility of monitoring tacrolimus blood concentrations in liver transplant patients

    J Clin Pharmacol

    (2001)
  • M. Ahmed et al.

    Quantitation of immunosuppression by tacrolimus using flow cytometric analysis of interleukin-2 and interferon-gamma inhibition in CD8(−) and CD8(+) peripheral blood T cells

    Ther Drug Monit

    (2001)
  • P.R. Sottong et al.

    Measurement of T-lymphocyte responses in whole blood cultures using newly synthesized DNA and ATP

    Clin DiagLab Immunol

    (2000)
  • R. Kowalski et al.

    Immune cell function testing: An adjunct to therapeutic drug monitoring in transplant patient management

    Clin Transplant

    (2003)
There are more references available in the full text version of this article.

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S. Hwang and K.H. Kim equally contributed as co-first authors for this study.

This study was supported by the investigator research fund from the Korean Society for Transplantation and Asan Institute for Life Science.

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