Analysis of gene expression in gut mucosa after intestinal transplantation: selection of candidates for diagnosis of graft rejection

ZAMBERNARDI A; MEIER D; SCHIFFRIN M; RUMBO C; CAGNOLA H; SOLAR H; DOCENA G; CHIRDO F; GONDOLOSI G; RUMBO M

Buenos Aires

Congreso; 1st French –Argentine Immunology Congress SAI-FAIC; 2010

Sociedad Argentina de Inmunologia

Intestinal transplantation (ITx) is indicated in cases of irreversible intestinal failure and complications associated to total parenteral nutrition. In spite of immunosuppressive treatment, acute cellular rejection (ACR) is a frequent complication and a first cause of graft loss. Graft monitoring by protocol biopsies is usually used for early detection of ACR by histological analysis. So far, no biochemical markers to detect ACR are available. Our aim was to characterize the ACR process by analyzing gene expression in the intestinal mucosa during follow up and to select candidate markers of rejection. Expression of Mx1, IFN-g, CXCL10, CXCL11, CXCR3, and CCL20 was measured by RT-qPCR in graft biopsies obtained during the first year follow-up of ITx patients. 42 samples of 9 patients were analyzed, including 10 ACR events, ranging from mild to severe and 2 episodes of enteral viral infection. In samples taken during severe ACR, induction of IFN-g (fold increase range (FIR) 3 to 7, depending on individual sample), CXCL11 (FIR 8 to 12), CXCL10 (FIR 3 to 18), and CCL20 (FIR 1 to 23) Mx-1 (2 to 24) was observed. Mild rejection episodes were not reflected by significant fold increase of the markers analyzed. Overall induction levels correlate with the severity of the rejection episode and the immunosuppressive management of the patient. Different viral enteritis caused increase of the different markers analyzed. Antiviral gene Mx-1 showed no specificity of viral infections. In some cases, CXCL11 expression levels showed a rise before ACR indicating that these genes might be putative predictors of rejection in the clinics. Although a wider set of analysis is necessary, our results demonstrate that graft gene expression analysis reflect that T cell-attracting chemokines are induced during a severe ACR. Therefore, this analysis might be a valuable tool for ACR characterization and eventual selection of candidate markers.