Systemic and cell type-specific gene expression patterns in scleroderma skin.
We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease.
Whitfield
Michael L
ML
Department of Dermatology, University of California-San Francisco, San Francisco, CA 94143, USA.
Finlay
Deborah R
DR
Murray
John Isaac
JI
Troyanskaya
Olga G
OG
Chi
Jen-Tsan
JT
Pergamenschikov
Alexander
A
McCalmont
Timothy H
TH
Brown
Patrick O
PO
Botstein
David
D
Connolly
M Kari
MK
D000328:Adult; D018951:Antigens, CD20 / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D045743:Scleroderma, Diffuse / Q000235:genetics* / Q000276:immunology; D012867:Skin / Q000276:immunology / Q000378:metabolism
D018951:Antigens, CD20