Genes Involved Cell Interactions are Differentially Expressed During Human Corneal Transplant Rejection

Abstract

Abstract: : Purpose: The aim of this study was to identify genes that are differentially expressed in cell interactions in peripheral blood during corneal graft rejection . Methods: cDNA array technology (Atlas Human Cell Interaction Array, BD Biosciences) was used to screen the gene expression changes in blood from corneal graft patients undergoing graft rejection compared to patients whose grafts were not rejected. Semi–quantitative RT–PCR was used to confirm differential expression of selected genes identified by the array results. Results: Among 265 genes on the array, several showed a 2 fold or greater difference in expression. The most apparent change in the rejecting group was the up–regulation of the Rac2 gene, coding for a small guanosine triphosphatase which plays a role in T cell differentiation. There was also down regulation of the following genes; 1. LFA–1, a member of the integrin family, which binds ICAM–1 and is known to be involved in corneal graft rejection. 2. Paxillin, a focal adhesion protein that recruits adhesion and growth factor mediated signals from the extracellular matrix. RT–PCR further confirmed that there were significant differences between rejecting and non–rejecting groups, for all three genes. Serial samples were available for several patients who suffered an episode of rejection. The levels of Rac2 and LFA–1 mRNA were shown to return to normal after treatment and resolution of the rejection Conclusions: Our data demonstrates that cDNA array technology can identify genes that may participate in the pathogenesis of corneal graft rejection. These genes may be useful prognostic markers of rejection or targets of new more specific treatments.

Keywords: cornea: clinical science • transplantation