Abstract
Both antibody mediated (AMR) and T-cell mediated (TCMR) rejections either acute or chronic represent the main reason for late graft dysfunction. In this study we aimed to evaluate differences in the intrarenal expression patterns of immune system related genes in acute and chronic rejections. Graft biopsies were performed and evaluated according to Banff classification. Using the TaqMan Low Density Array, the intrarenal expressions of 376 genes relating to immune response (B-cell activation, T-cell activation, chemokines, growth factors, immune regulators, and apoptosis) were analyzed in the four rejection categories: chronic AMR, chronic TCMR, acute AMR, and acute TCMR. The set of genes significantly upregulated in acute TCMR as compared to acute AMR was identified, while no difference in gene expressions between chronic rejections groups was found. In comparison with functioning grafts, grafts that failed within the next 24 months after the chronic rejection morphological confirmation presented at biopsy already established severe graft injury (low eGFR, higher proteinuria), longer followup, higher expression of CDC20, CXCL6, DIABLO, GABRP, KIAA0101, ME2, MMP7, NFATC4, and TGFB3 mRNA, and lower expression of CCL19 and TRADD mRNA. In conclusion, both Banff 2007 chronic rejection categories did not differ in intrarenal expression of 376 selected genes associated with immune response.
Highlights
Both acute and chronic rejections have been shown to affect the long-term outcome of kidney transplantation
Both acute and chronic rejections were shown to be associated with several patterns of immune system related gene transcripts
interferon gamma (IFNG)-inducible and cytotoxic T-cell associated transcripts were upregulated in the acute T-cell mediated rejection (TCMR) that is in line with the observation of others [5, 6]
Summary
Both acute and chronic rejections have been shown to affect the long-term outcome of kidney transplantation. Chronic active antibody mediated rejection (CAMR) is characterized by C4d deposition in peritubular capillaries, the presence of circulating anti-donor antibodies, and morphologic evidence of chronic tissue injury such as glomerular double contours and peritubular capillary basement membrane multilayering and interstitial fibrosis/tubular atrophy (IF/TA) and fibrous arterial intimal thickening. The diagnosis of this entity is problematic since C4d deposits are not permanent and antibody mediated rejection was described to be associated with different pathways where C4d is not involved [2]. In this study we aimed for evaluation of molecular signatures of acute and chronic rejections categories and for evaluation of association of gene transcripts with kidney graft loss due to chronic rejection
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
