Expression of surfactant protein-C, S100A8, S100A9, and B cell markers in renal allografts: investigation of the prognostic value.
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 beta-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.
Eikmans
Michael
M
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Roos-van Groningen
Marian C
MC
Sijpkens
Yvo W J
YW
Ehrchen
Jan
J
Roth
Johannes
J
Baelde
Hans J
HJ
Bajema
Ingeborg M
IM
de Fijter
Johan W
JW
de Heer
Emile
E
Bruijn
Jan A
JA
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D040501:Calgranulin A / Q000235:genetics / Q000378:metabolism*; D040502:Calgranulin B / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D011336:Probability; D011379:Prognosis; D011486:Protein C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D013501:Surface-Active Agents / Q000378:metabolism; D014184:Transplantation, Homologous
D040501:Calgranulin A; D040502:Calgranulin B; D005819:Genetic Markers; D011486:Protein C; D012333:RNA, Messenger; D013501:Surface-Active Agents; D005914:Globins