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Expression of Surfactant Protein-C, S100A8, S100A9, and B Cell Markers in Renal Allografts: Investigation of the Prognostic Value

Michael Eikmans^*, Marian C. Roos-van Groningen^*, Yvo W.J. Sijpkens, Jan Ehrchen, Johannes Roth^,, Hans J. Baelde^*, Ingeborg M. Bajema^*, Johan W. de Fijter, Emile de Heer^* and Jan A. Bruijn^*

^* Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands; Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands; and Institute of Experimental Dermatology; and Department of Pediatrics, University of Münster, Munich, Germany

Address correspondence to: Dr. Michael Eikmans, Leiden University Medical Center, Department of Pathology, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands. Phone: +31-71-526-6574; Fax: +31-71-524-8158; m.eikmans{at}lumc.nl

Received for publication April 19, 2005. Accepted for publication September 15, 2005.

The intent of this study was to identify genes of which expression during acute rejection is associated with progression to chronic allograft nephropathy using gene expression profiling. Ten patients who had graft loss through chronic allograft nephropathy (progression [PR] group) and 18 patients who had stable graft function over time (nonprogression [NP] group) were studied. Rejection severity and extent of infiltrating leukocytes in acute rejection biopsies were similar for both groups. Microarray analysis and real-time PCR validation showed that surfactant protein-C (SP-C), S100 calcium-binding protein A8 (S100A8), S100A9, and -globin levels distinguished the two groups. Relationship between expression of B cell markers and prognosis was also examined. Location in the graft of the protein and mRNA expression of candidate genes was investigated. The prognostic value of mRNA transcripts was tested in an independent cohort of 43 rejection biopsies. mRNA and protein expression of S100A8 and S100A9 in infiltrating cells was significantly higher in the NP group compared with the PR group. Expression of SP-C was four-fold higher in the PR group and was detected in glomeruli. No association between B cell clusters and outcome was found. In the second group of acute rejection biopsies, SP-C mRNA levels predicted renal function course beyond 6 mo in multivariate analysis. Relatively high expression of S100A8 and S100A9 during acute rejection is associated with a favorable prognosis, and high SP-C expression is associated with an unfavorable prognosis. Messenger RNA transcripts complement the biopsy in the prediction of graft function deterioration.

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673