Clinical

ImmuKnow assay helps gauge infection risk in liver transplant recipients

Last Updated: 2012-10-24 13:45:07 -0400 (Reuters Health)

By Megan Brooks

NEW YORK (Reuters Health) - The ImmuKnow assay (Cylex Inc) is a "valid" tool for determining the risk of infection in adult liver transplant recipients, and may be helpful in predicting acute rejection as well, report researchers from Spain.

The ImmuKnow assay measures increases in intracellular adenosine triphosphate (iATP) after CD4 cell activation. It is FDA approved for determining cell-mediated immunity in solid-organ transplant recipients on immunosuppression. It helps identify transplant patients at risk for infection due to over-immunosuppression and guide decisions in therapy to avoid over- or under-immunosuppression, the manufacturer explains on its web site.

Dr. Emilio Rodrigo and colleagues from Marques de Valdecilla University Hospital, University of Cantabria, Santander, Spain did a systemic review and meta-analysis to investigate the diagnostic accuracy of the ImmuKnow test for predicting the risk of infection and acute rejection in liver transplant recipients. "Although the ImmuKnow test was not developed as a diagnostic test for infection or acute rejection, it was developed to estimate the risk of both," they point out.

They identified five studies that analyzed ImmuKnow performance for infection in 651 patients and another five that tested ImmuKnow performance for acute rejection in 543 patients.

In a report in Liver Transplantation, the authors say the results indicate that the ImmuKnow test result is "clearly" related to the further development of infection in liver transplant recipients. The overall accuracy of ImmuKnow for predicting infection is "good," they say, with a sensitivity of 83.8% and a specificity of 75.3%."

According to the diagnostic odds ratio (DOR), transplant recipients with a positive ImmuKnow result have a 14.6 times higher likelihood of developing an infection than patients with a negative test result. "Similarly, a positive likelihood ratio of 3.3 suggests that a positive ImmuKnow result significantly increases the post test probability of infection, and the area under the SROC curve shows the good diagnostic performance of this test for infection after liver transplantation," the authors say.

"These results," they point out, "are more remarkable when we take into account that ImmuKnow was designed not as a diagnostic test for infection but as a way of monitoring the global immunosuppressive status."

In contrast, the performance of the test for acute rejection was not fully demonstrated by the data, the authors say. They say they found a "high degree of heterogeneity attributable to real differences among the studies rather than chance."

Despite the lack of homogeneity, the significant sensitivity (65.6%), specificity (80.4%) and DOR (3.4) "suggest a possible role for the ImmuKnow test in predicting the development of acute rejection," the authors emphasize.

"Our study," they say, "does not rule out that the ImmuKnow test is related to further acute rejection; it shows only that it is not possible to conclude this issue because of the significant heterogeneity of the included studies. The clear relationship with infections in liver transplant recipients and the possible relationship with acute rejection suggest that the ImmuKnow test could be a useful tool for determining the immunological status of these patients."

Dr. Rodrigo did not respond to a request for comment by press time.

Reuters Health did reach Dr. Richard Kowalski, director of medical affairs for Cylex. In an email, he said he "initially read this paper when it was an accepted electronic copy and found that it is a well written and researched meta-analysis on the use to the ImmuKnow assay in adult liver transplant recipients."

"Clearly low ImmuKnow values are associated with infections likely due to over-immunosuppression. However, the heterogeneity with both ImmuKnow values and definitions of cellular rejection make the associations of elevated ImmuKnow values with rejection less clear. My opinion is that this article supports the use of ImmuKnow as a tool to detect cell-mediated immunity and to assign a level of immunological risk based on sequential measurements," Dr. Kowalski said.

The study was supported by the Carlos III Institute of Health and the Institute for Training and Research of the Marques de Valdecilla Foundation. The authors have declared no conflicts of interest.

SOURCE: http://bit.ly/SsMuzB

Liver Transpl 2012;18:1245-1253.