title: Characterization of heterogeneity in the molecular pathogenesis of lupus nephritis from transcriptional profiles of laser-captured glomeruli.
abstract: The molecular pathogenesis of focal/diffuse proliferative lupus glomerulonephritis was studied by cDNA microarray analysis of gene expression in glomeruli from clinical biopsies. Transcriptional phenotyping of glomeruli isolated by laser-capture microscopy revealed considerable kidney-to-kidney heterogeneity in increased transcript expression, resulting in four main gene clusters that identified the presence of B cells, several myelomonocytic lineages, fibroblast and epithelial cell proliferation, matrix alterations, and expression of type I IFN-inducible genes. Glomerulus-to-glomerulus variation within a kidney was less marked. The myeloid lineage transcripts, characteristic of those found in isolated activated macrophages and myeloid dendritic cells, were widely distributed in all biopsy samples. One major subgroup of the samples expressed fibrosis-related genes that correlated with pathological evidence of glomerulosclerosis; however, decreased expression of TGF-beta1 argued against its role in lupus renal fibrosis. Expression of type I IFN-inducible transcripts by a second subset of samples was associated with reduced expression of fibrosis-related genes and milder pathological features. This pattern of gene expression resembled that exhibited by activated NK cells. A large gene cluster with decreased expression found in all samples included ion channels and transcription factors, indicating a loss-of-function response to the glomerular injury.
authors.affiliation: Department of Pediatrics, Columbia University, New York, New York 10032, USA. ksp4@columbia.edu
authors.forename: Karin S
authors.initials: KS
authors.lastname: Peterson
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Huang
authors.forename: Jessica
authors.initials: J
authors.lastname: Zhu
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.forename: Xuejun
authors.initials: X
authors.lastname: Liu
authors.forename: Nancy
authors.initials: N
authors.lastname: Miller
authors.forename: Mark G
authors.initials: MG
authors.lastname: Erlander
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jackson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Winchester
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007678:Kidney Glomerulus / Q000276:immunology / Q000502:physiology* / Q000601:surgery / Q000648:ultrastructure*; D007834:Lasers; D008181:Lupus Nephritis / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012044:Regression Analysis; D014158:Transcription, Genetic