CD4+ T-Lymphocyte Adenosine Tri-Phosphate(ATP) Levels in Pediatric Patients with Crohnʼs Disease: A New Marker for Disease Activity

Abstract

Purpose: Crohn's disease (CD) is a chronic inflammatory condition involving any segment of the gastrointestinal tract with an incidence of 3.5-4.5 per 100,000 children. The successful management of severe CD requires adequate suppression of the immune system with immunosuppressants and/ or biologics. CD4+ T-lymphocyte ATP levels correlates with immunoreactivity and have been used to monitor cell-mediated immunity in patients with solid organ transplantation. Our hypothesis is that lower ATP levels correlate with sufficient immunosuppression and better disease control. Methods: Serial CD4+ ATP levels (n=54) were prospectively obtained from 19 pediatric patients on immunosuppressive therapy for CD at the time of their follow up visits. CD4+ ATP levels were performed using the Cylex ImmuKnow assay. Results: The mean age of our cohort was 15.6 years(±4.7) with 57.9% male and 84.2% Caucasian. Their CD was ileocolonic in 52.6%, colonic in 42.2%, and limited to the small bowel in 5.2%. All our patients were on immunomodulators and 9 patients (47.3%) were also on infliximab. Patients were seen between 1 to 5 times with a mean follow up time of 6.2 months. The mean ATP level was 496 ng/dL(±158.3). CD4+ ATP levels were found to be significantly associated with PCDAI and ESR. Mean ATP levels increased by 8.7 units for every 1 unit increase in the PCDAI (p<0.001). In addition, for every 1 unit increase in ESR, the mean ATP value increased by 4.6 units (p=0.007). Of note, in patients with serial ATP measurments, lower ATP levels were observed after increasing the dose of immunomodulators or increasing the dosing freqency of infliximab. Conclusion: CD4+ ATP levels correlate with PCDAI and high CD4+ ATP levels may reflect sub-optimal immunosuppression in patients with CD. This simple test can help guide the management of immunosuppressive therapy in this population.