Elsevier

Transplant Immunology

Volume 37, July 2016, Pages 35-39
Transplant Immunology

Clinical utility of CD4 + function assessment (ViraCor-IBT ImmuKnow test) in lung recipients

https://doi.org/10.1016/j.trim.2016.04.001Get rights and content

Highlights

  • Lower Immuknow level in lung recipients correlates with higher risk of infections.

  • An interesting association was found between RAS and low Immuknow level.

  • Immuknow assay is an useful tool to adjust the immune response in lung recipients.

Abstract

The ImmuKnow assay measures cell-mediated immunity, quantifying ATP production from peripheral blood CD4 + T-cells in solid-organ transplant patients who undergo immunosuppressive therapy. We aimed to measure functional immunity in lung transplant recipients and correlate Immuknow values with immunosuppression levels, presence of chronic lung allograft dysfunction (CLAD) and infections. We evaluated 61 lung recipients who underwent follow-up for lung transplantation between 2010 and 2014. Rejection and infection were retrospectively analyzed. The association between over-immunosuppression and a number of predictors was assessed by means of univariate and multivariate logistic regression models. 71 out of 127 samples (56%) showed an over-immunosuppression with an ImmuKnow assay mean level of 112.92 ng/ml (SD ± 58.2), vs. 406.14 ng/ml (SD ± 167.7) of the rest of our cohort. In the over-immunosuppression group we found 51 episodes of infection (71%) (OR 2.754, 95% CI 1.40–5.39; P-value 0.003). In the other group, only 25 samples (44%) were taken during an infectious episode. The mean absolute ATP level was significantly different between patients with or without infection (202.38 ± 139.06 ng/ml vs. 315.51 ± 221.60 ng/ml; P < 0.001). RAS (Restrictive allograft syndrome) was associated to low ImmuKnow level (P < 0.001). These results were confirmed by the multivariate analysis. The ImmuKnow assay levels were significantly lower in infected lung transplant recipients compared with non-infected recipients and in RAS patients.

Section snippets

Background

Lung transplantation is an accepted treatment for end-stage lung diseases. Nowadays, the main issue is to achieve an acceptable long-term survival after surgery, and the greatest impediment to improve long-term survival is chronic lung allograft dysfunction (CLAD).Recent evidence pointed out that both aspecific (such as infections) and allospecific lung injuries (acute rejection episodes) are significant risk factors for the occurrence of CLAD [1]. According to recent classification, there are

Patients

61 patients who underwent follow-up for lung transplantation between 2010 and 2014 were included in the IMK study. Features of the included patients are shown in Table 1. At our center, during routine lung transplant follow-up visits, patients undergo complete clinical evaluation; blood tests, respiratory function tests, the assessment of serum trough levels of IS drugs and lymphocyte subsets on peripheral blood. IMK assay was performed at 6 month FU, only for the patients who entered the study

Results

Our population included 47 males and 14 females. The mean age at the time of follow-up was 47 years. Underlying diseases were Idiopathic pulmonary fibrosis/NSIP (n = 27), COPD/Emphysema (n = 13), Pulmonary hypertension (n = 6), Cystic fibrosis (n = 5), Bronchiectasis (n = 3), Ebstein's disease/Eisenmenger Syndrome (n = 3), CLAD/RE-Tx (n = 2), Combined pulmonary fibrosis and emphysema (n = 1), and Lymphangioleiomyomatosis (n = 1). 23 patients underwent single lung transplant, 35 patients underwent double lung

Discussion

One of the major challenges in lung transplantation is balancing immunosuppression in order to avoid drug toxicities and complications of over- and under-immunosuppression. During the past years, several clinical trials of the use of IMK have shown that it is able to detect and measure the rate of “over-IS” of CD4 + cells in solid organ transplant patients, such as the kidney, heart, small bowel and pancreas. All these studies demonstrated the promise of IMK in solid-organ transplant recipients,

Acknowledgment

The authors thank Dr. Katherine O'Donohoe for careful revision of the manuscript.

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