Gene expression profiles of circulating leukocytes correlate with renal disease activity in IgA nephropathy.
BACKGROUND
The goal of these studies was to explore the possibility of using gene expression profiles of circulating leukocytes as a functional fingerprint of nephritic disease activity.


METHODS
This feasibility study utilized IgA nephropathy (IgAN) as a model system. Genes differentially expressed in IgAN patients were identified by Affymetrix GeneChip microarrays, and compared with gene expression of focal segmental glomerulosclerosis (FSGS), minimal change disease, antineutrophil cytoplasmic antibody (ANCA) glomerulonephritis, and with healthy volunteers. Of the genes identified, 15 transcriptionally up-regulated were validated in a larger cohort of patients using TaqMan polymerase chain reaction (PCR). To test whether increased expression of these genes correlated with disease activity, cluster analyses were performed utilizing the TaqMan PCR values. Taking a mathematical approach, we tested whether gene expression values were correlative with kidney function, as reflected by serum creatinine and creatinine clearance values.


RESULTS
We identified 15 genes significantly correlative with disease activity in IgAN. This gene signature of IgAN patients' leukocytes reflected kidney function. This was demonstrated in that mathematically generated theoretical values of serum creatinine and creatinine clearance correlated significantly with actual IgAN patient values of serum creatinine and creatinine clearance. There was no apparent correlation with hematuria and proteinuria. The expression levels of this same gene set in ANCA glomerulonephritis or Lupus nephritis patients were not correlative with serum creatinine or creatinine clearance values.


CONCLUSIONS
These data indicate that leukocytes carry informative disease-specific markers of pathogenic changes in renal tissue.
Preston
Gloria A
GA
Department of Medicine, Division of Nephrology and Hypertension, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7155, USA. Gloria_Preston@med.unc.edu
Waga
Iwao
I
Alcorta
David A
DA
Sasai
Hitoshi
H
Munger
William E
WE
Sullivan
Pamela
P
Phillips
Brian
B
Jennette
J Charles
JC
Falk
Ronald J
RJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers; D002648:Child; D003404:Creatinine / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000502:physiology; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D012044:Regression Analysis
D015415:Biomarkers; D003404:Creatinine