Blood test cuts infection risk in transplant patients


Over the years, long-term use of immunosuppressive medications has shown that they reduce morbidity and mortality in transplant patients. One of physicians' challenges is to balance the risk of organ rejection caused by underimmunosuppression with the risk of drug toxicity, secondary infections, and posttransplant lymphoproliferative disorders caused by overimmunosuppressing the patient.

Until recently, immunosuppressive drug levels have been used to prevent toxicity, but not for preventing rejection or infection. "There are tests to monitor the levels of immunosuppressives, but they do not assess the patient's immune status if he or she is on a combination of immunosuppressives," said Adriana Zeevi, Ph.D., professor of pathology and surgery and codirector of the Tissue Typing Laboratory at the University of Pittsburgh.

ImmuKnow (Cylex Inc.) is a blood test just cleared by the Food & Drug Administration that is designed to measure the strength of a patient's immune system from a single drop of blood. The assay detects cell-mediated immunity in immunocompromised patients by detecting intracellular adenosine triphosphate (ATP) synthesis in CD4 cells. ATP is a key marker of immune function, can be used to measure lymphocyte activity, and is a source of energy for cells. Because the CD4 lymphocytes coordinate cell-mediated responses through immunoregulatory signaling, the measurement of CD4 activation reflects the degree of immune cell function.

The cellular immune response of the assay is made by comparing the ATP concentration of the blood specimen to fixed ATP level ranges. The ATP level ranges for ImmuKnow were established by testing 155 healthy adults and 127 transplant recipients with the assay. A cumulative frequency of the differences was used to select the ATP levels that give the best balance of results between immunocompromised and nonimmunocompromised individuals.

There are three measurable immunological response zones: strong, weak, and the target zone, which is associated with minimal risk of clinical complications. An ATP level of 225 ng/ml or less corresponds to a low immune response, while an ATP level of 525 ng/ml or more corresponds to a strong immune response. The target zone is defined as an ATP level between 226-524 ng/ml.

Cylex recommends that the results of the test be used in conjunction with clinical presentation and the patient's medical history as well as other clinical indicators when establishing the patient's immune status.

Some patients are too immunosuppressed, which can lead to lethal infections and to withholding or decreasing the dose of the medications. One of the major challenges of reducing the dose of immunosuppressives is how rapidly to assess the impact on a patient's immune system. "This assay allows physicians to see when the patient's immune system is responding, so we are able to maintain the patient on a stable status," she added.

A recent meta-analysis, published in the Sept. 15 issue of Transplantation, discusses the results of 504 solid organ transplant patients using the ImmuKnow assay. The analysis showed that patients with an ATP level of 25 ng/ml were 12 times more likely to develop an infection, while patients with an ATP level of 700 ng/ml were 30 times more likely to reject the transplanted organ. Patients who maintained ATP levels between 130 and 450 ng/ml were at minimal risk for infection or rejection, with a target value of 280 ng/ml. At this level, the patient would have a 96% chance of avoiding infection or organ rejection.

The manufacturer states that one of the limitations of the assay is that ImmuKnow results may be unpredictable in some patients immediately following transplantation because of immune system instability caused by surgical trauma, anesthesia, transfusion, or lymphopenia.

Zeevi believes that cost is not an issue with the use of the product. "The main advantage of this assay is that it helps decrease toxicity from immunosuppressives," she commented.

Related Videos
fake news misinformation | Image Credit: Bits and Splits -
© 2024 MJH Life Sciences

All rights reserved.