Individualized immune monitoring of cardiac transplant recipients by noninvasive longitudinal cellular immunity tests.
BACKGROUND
Common immunosuppression strategies after heart transplantation (HTx) are based on accepted target drug levels, disregarding that drug levels do not correlate with the individual patient's pharmacokinetics or with the actual immunosuppressive drug effect on the patient. The Immuknow assay is used for immune monitoring and management of organ transplant recipients. This study evaluated the Immuknow assay for longitudinal immune monitoring of HTx patients throughout various clinical settings.


METHODS
The functional immune response as measured by the Immuknow assay was determined in 327 samples collected from 50 HTx patients at the Rabin Medical Center and was analyzed together with common clinical parameters.


RESULTS
The median Immuknow levels measured throughout the infection episodes and the episodes of biopsy-proven acute rejection were 129 and 619 ng ATP/mL, respectively. These values were significantly dissimilar to the median Immuknow level measured during clinical quiescence, which was 351 ng ATP/mL (P<0.05). Calcineurin inhibitors drug-level measurements did not provide a reliable depiction of the patients' immune function, because the median deviation from the recommended drug trough levels range was significantly higher than the median deviation of Immuknow levels from their expected immune response zones. Longitudinal monitoring of Immuknow levels through serial testing proved to be a reliable method for individual patient immune management.


CONCLUSIONS
The Immuknow assay reliably reflects the cellular immune function of HTx patients, thereby supporting the immune monitoring and management of these patients. Serial longitudinal Immuknow monitoring allows immune management of therapy according to the individual patient's immune status.
Israeli
Moshe
M
Tissue Typing Laboratory, Rabin Medical Center, Petach-Tikva, Israel. mosheis@clalit.org.il
Ben-Gal
Tuvia
T
Yaari
Vicktoria
V
Valdman
Andrei
A
Matz
Israel
I
Medalion
Benjamin
B
Battler
Alexander
A
Sredni
Benjamin
B
Kristt
Don
D
Klein
Tirza
T
D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D003141:Communicable Diseases / Q000276:immunology; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects*; D007159:Immunologic Tests; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents; D000255:Adenosine Triphosphate