Differential cytokine and chemokine expression during rejection and infection following intestinal transplantation

Abstract

Background/objectivesRejection and infectious enteritis in intestinal transplant (ITx) patients present with virtually identical symptoms. Currently, the gold standard for differentiating between these two conditions is endoscopy, which is invasive and costly. Our primary aim was to identify differences in peripheral blood cytokines during episodes of acute cellular rejection (ACR) and infectious enteritis in patients with intestinal transplants. MethodsThis was a prospective, cross-sectional study involving ITx patients transplanted between 2000 and 2016. We studied 63 blood samples collected from 29 ITx patients during periods of normal (n = 24) and abnormal (n = 17) allograft function. PBMCs from whole blood samples were cultured under unstimulated or stimulated conditions with phytohemagglutinin (PHA). The supernatant from these cultures were collected to measure cytokine and chemokine levels using a 38-plex luminex panel. ResultsOur study found that cytokines and chemokines are differentially expressed in normal, ACR, and infectious enteritis samples under unstimulated conditions based on heatmap analysis. Although each cohort displayed distinctive signatures, only MDC (p = 0.037) was found to be significantly different between ACR and infectious enteritis. Upon stimulation of PBMCs, patients with ACR demonstrated increased immune reactivity compared to infectious enteritis; though this did not reach statistical significance. ConclusionsTo our knowledge, this is the first comprehensive study comparing cytokine expression during acute rejection and infectious enteritis in intestinal transplant recipients. Our results suggest that cytokines have the potential to be used as clinical markers for risk stratification and/or diagnosis of ACR and infectious enteritis.