Molecular profile of peripheral blood mononuclear cells from patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic inflammatory arthritis. Currently, diagnosis of RA may take several weeks, and factors used to predict a poor prognosis are not always reliable. Gene expression in RA may consist of a unique signature. Gene expression analysis has been applied to synovial tissue to define molecularly distinct forms of RA; however, expression analysis of tissue taken from a synovial joint is invasive and clinically impractical. Recent studies have demonstrated that unique gene expression changes can be identified in peripheral blood mononuclear cells (PBMCs) from patients with cancer, multiple sclerosis, and lupus. To identify RA disease-related genes, we performed a global gene expression analysis. RNA from PBMCs of 9 RA patients and 13 normal volunteers was analyzed on an oligonucleotide array. Compared with normal PBMCs, 330 transcripts were differentially expressed in RA. The differentially regulated genes belong to diverse functional classes and include genes involved in calcium binding, chaperones, cytokines, transcription, translation, signal transduction, extracellular matrix, integral to plasma membrane, integral to intracellular membrane, mitochondrial, ribosomal, structural, enzymes, and proteases. A k-nearest neighbor analysis identified 29 transcripts that were preferentially expressed in RA. Ten genes with increased expression in RA PBMCs compared with controls mapped to a RA susceptibility locus, 6p21.3. These results suggest that analysis of RA PBMCs at the molecular level may provide a set of candidate genes that could yield an easily accessible gene signature to aid in early diagnosis and treatment.
Edwards
Christopher J
CJ
The Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, London, UK. cedwards@soton.ac.uk
Feldman
Jeffrey L
JL
Beech
Jonathan
J
Shields
Kathleen M
KM
Stover
Jennifer A
JA
Trepicchio
William L
WL
Larsen
Glenn
G
Foxwell
Brian Mj
BM
Brennan
Fionula M
FM
Feldmann
Marc
M
Pittman
Debra D
DD
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D005453:Fluorescence; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008875:Middle Aged; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic
D012313:RNA