Korean J Hepatobiliary Pancreat Surg.  2015 Nov;19(4):139-148. 10.14701/kjhbps.2015.19.4.139.

In vitro immune cell monitoring as a guide for long-term immunosuppression in adult liver transplant recipients

• Jwa E
• Hwang S
• Kwon YJ
• Kim N
• Song GW
• Jung DH
• Ahn CS
• Tak E
• Moon DB
• Kim KH
• Ha TY
• Park GC
• Lee SG

• KMID: 2130965
• DOI: http://doi.org/10.14701/kjhbps.2015.19.4.139

Abstract

BACKGROUNDS/AIMS
We evaluated the clinical usability of immune cell monitoring in adult liver transplantation (LT) recipients.
METHODS
This study was composed of two parts as using calcineurin phosphatase (CNP) activity assay and ImmuKnow assay independently as in vitro monitoring tools of immune cell function in adult LT recipients.
RESULTS
There was a rough correlation between CNP activity and tacrolimus concentration in 33 patients. This association was evident in patients who were only administered tacrolimus, but disappeared after the co-administration of mycophenolate. In 118 healthy individuals, the mean proportion of helper T-cells was 37.4+/-8.1%. According to ImmuKnow assay, their immune responses were strong in 12 patients (10.2%), moderate in 92 patients (78.0%), and low in 14 patients (11.9%). In 85 patients waiting for LT, there was a rough correlation between the ImmuKnow ATP level and age. Their immune responses were strong in 0 patients (0%), moderate in 8 patients (9.4%), and low in 77 patients (90.6%). There was a difference in the ImmuKnow ATP levels between healthy individuals and patients with liver disease. In 137 LT recipients, there was no correlation between the ImmuKnow ATP levels and tacrolimus concentration. This trend did not change after grouping the patients according to co-administration with mycophenolate. Eight recipients experienced acute rejection, but none showed strong immune response.
CONCLUSIONS
We think that both CNP activity assay and ImmuKnow assay are too limited to objectively determine the level of immunosuppression. Further studies should be performed to identify other methods for immune function monitoring.

Keyword

Calcineurin phosphatase; Tacrolimus; Rejection; ImmuKnow; Operational tolerance

MeSH Terms

Adenosine Triphosphate
Adult*
Calcineurin
Humans
Immunosuppression*
Liver Diseases
Liver Transplantation
Liver*
T-Lymphocytes, Helper-Inducer
Tacrolimus
Transplantation*
Adenosine Triphosphate
Calcineurin
Tacrolimus

Figure

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  Fig. 1 Scatterplot graph showing the correlation between the 12-hour trough tacrolimus concentration and calcineurin phosphatase (CNP) activity in 33 patients. The dotted line indicates the regression equation.

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  Fig. 2 Scatterplot graphs showing the correlation between the 12-hour trough tacrolimus concentration and calcineurin phosphatase (CNP) activity in (A) 17 patients who were administered tacrolimus and mycophenolate mofetil and (B) 15 patients who were administered only tacrolimus. The dotted lines indicate the regression equations.

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  Fig. 3 Scatterplot graph showing the distributions of the proportions of helper T-cells according to age in 118 healthy individuals. The dotted line indicates the regression equation.

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  Fig. 4 Scatterplot graph showing the distribution of ImmuKnow ATP levels according to age in 118 healthy individuals. In the right column, the ranges of the immune responses are depicted according to the predefined ImmuKnow criteria. The dotted line indicates the regression equation.

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  Fig. 5 Scatterplot graphs showing the distribution of ImmuKnow ATP levels according to age in (A) 76 healthy male individuals and (B) 42 healthy female individuals. The dotted lines indicate the regression equations.

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  Fig. 6 Scatterplot graph showing the distribution of ImmuKnow ATP levels according to age in 85 adult patients with end-stage liver disease waiting for liver transplantation. The ranges of the immune responses are depicted in the right column. The dotted line indicates the regression equation.

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  Fig. 7 Scatterplot graph showing the distribution of ImmuKnow ATP levels according to the 12-hour trough tacrolimus concentration in 137 liver transplant recipients. The ImmuKnow assay was performed 543 times on these 137 patients (mean 4 times). In the right column, the ranges of immune responses are depicted. The dotted line indicates the regression equation.

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  Fig. 8 Scatterplot graphs showing the distributions of ImmuKnow ATP levels according to the 12-hour trough tacrolimus concentrations in (A) 73 patients who were administered tacrolimus and mycophenolate mofetil and (B) 64 patients who were only administered tacrolimus. The dotted lines indicate the regression equations.

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