Received December 16, 2008
Accepted on July 14, 2009

CLINICAL RESEARCH

Molecular Phenotypes of Acute Rejection Predict Kidney Graft Prognosis

Ondrej Viklicky ^*1, Petra Hribova ^*, Hans-Dieter Volk , Janka Slatinska , Jan Petrasek ^||, Stepan Bandur ^*, Eva Honsova ^¶, and Petra Reinke ^**

*Transplant Laboratory, Department of Nephrology, ¶Department of Clinical and Transplant Pathology, and ||Laboratory of Experimental Hepatology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; and Institute of Medical Immunology, **Department of Nephrology and Intensive Medicine, and Berlin–Brandenburg Center for Regenerative Therapies, University Medicine Charité, Berlin, Germany

¹ To whom correspondence should be addressed. E-mail: ondrej.viklicky{at}medicon.cz.

	Abstract

Earlier detection of antibody-mediated rejection of kidney allografts may improve graft outcomes. Profiling of gene expression holds promise for the diagnosis and prognosis of antibody-mediated rejection. Here, we identified 730 patients who received kidney transplants during 2002–2005, including 21 patients (2.9%) who experienced early acute antibody-mediated rejection. We also identified a matched group of 43 patients with early acute T cell-mediated rejection to serve as controls. Compared with patients with T cell-mediated rejection, those with antibody-mediated rejection had significantly higher intrarenal mRNA expression of the cytoprotective heme oxygenase-1 but had lower expression of the regulatory T cell marker forkhead box P3 (FoxP3), the B cell marker CD20, and the chemokine regulated upon activation, normal T cell expressed and secreted (RANTES). T cell infiltration was similar in both groups of patients. Compared with grafts that had a favorable course, those that failed as a result of antibody-mediated rejection had expression profiles suggesting a lack of regulation (less FoxP3, TGF-1, RANTES, and CD20). Grafts that failed as a result of T cell-mediated rejection only revealed lower expression of CD20 mRNA. In summary, these data suggest that severe antibody-mediated rejection and T cell-mediated rejection result in graft loss by distinct mechanisms. Molecular phenotypes of early acute rejection might help to identify grafts with poor prognosis, allowing earlier application of additional therapies.