Analisis de expresión de genes proinflamatorios en mucosa en el seguimiento postransplante intestinal. Correlación con histopatología, tratamiento inmunosupresor y rechazo.

AGUSTINA ZAMBERNARDI; DOMINIK MEIER; CABANNE, ANA; CHIODETTI ANA; CAROLINA RUMBO; SOLAR HECTOR; GONDOLESI GABRIEL; MARTIN RUMBO

Congreso; X Congreso of the Latin American Association of Immunology; 2012

Latin American Association of Immunology

Acute cellular rejection (ACR) is a major cause of graft loss after intestinal transplant. Clinical, endoscopic and histological findings obtained upon symptoms or routine follow-up procedures are used to diagnose ACR. Improving our understanding of the process and enlarging the diagnostic tools for ACR are desirable. With this aim, we analyzed the relative expression of several genes, markers of Th1, Th2 or Th17 immune response in graft biopsies taken during endoscopic follow-up post transplant. A total of 107 samples of 18 patients (7 adults / 11 pediatrics) recipients of isolated small bowel transplant were analyzed. Among them, 48 showed normal histopathology and clinical stability, 29 correspond to rejection episodes diagnosed by histopathology and the remaining 30 correspond to different clinical or histopathological conditions (viral infections, intrabdominal collections, pancreatitis, histology inderterminate for rejection) . Expression of INF-g CXCL11, CXCL10, IL-13 and IL-17 was quantified by RT-qPCR, using of b-actin as normalizer and using the group of normal samples as reference. Neither of the genes studied showed a specific increase of expression, since increments were detected either in rejection, infection or other inflammatory processes. However, histological changes were correlated with gene expression, finding an association of INF-γ with augmented infiltration of lymphocytes and plasma cells (INF-γ p < 0.0005) (CXCL10 p= 0.05328, CXCL11 p = 0.05147, NS for IL-13 and IL-17). Gene expression analysis is a valuable tool to understand the biological processes ongoing during ACR. Different clinical conditions such as infectious enteritis may influence the levels of expression of immune related genes and there is still missing a specific marker of rejection at the gene expression level. The analysis of a larger number of samples and incorporation of new genes will improve the characterization and help to the differential diagnosis of ACR vs infectious events that require opposed therapeutic strategies.