DNA microarray allows molecular profiling of rheumatoid arthritis and identification of pathophysiological targets.
This study was undertaken to evaluate the possibility to obtain a molecular signature of rheumatoid arthritis (RA) comparatively osteoarthritis (OA), and to lay the bases to develop new diagnostic tools and identify new targets. Microarray technology was used for such an analysis. The gene expression profiles of synovial tissues from patients with confirmed RA, and patients with OA were established and compared. A set of 63 genes was selected, based, more specifically, on their overexpression or underexpression in RA samples compared to OA. Results for six of these genes have been verified by quantitative PCR using both samples identical to those used in the microarray experiments and entirely separate samples. Expression profile of the 48 known genes allowed the correct classification of additional RA and OA patients. Furthermore, the distinct expression of three of the selected genes was also studied by quantitative RT-PCR in cultured synovial cells. Detailed analysis of the expression profile of the selected genes provided evidence for dysregulated biological pathways, pointed out to chromosomal location and revealed novel genes potentially involved in RA. It is proposed that such an approach allows valuable diagnosis/prognostics tools in RA to be established and potential targets for combating the disease to be identified.
Devauchelle
V
V
Institut Cochin, Paris, France.
Marion
S
S
Cagnard
N
N
Mistou
S
S
Falgarone
G
G
Breban
M
M
Letourneur
F
F
Pitaval
A
A
Alibert
O
O
Lucchesi
C
C
Anract
P
P
Hamadouche
M
M
Ayral
X
X
Dougados
M
M
Gidrol
X
X
Fournier
C
C
Chiocchia
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000503:physiopathology*; D056668:Cathepsin L; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D051152:Clusterin; D003546:Cysteine Endopeptidases; D053487:DEAD-box RNA Helicases; D017931:DNA Primers; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010003:Osteoarthritis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020365:RNA Helicases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013582:Synovial Fluid / Q000378:metabolism
C091247:BCAP31 protein, human; C495242:CLU protein, human; D051152:Clusterin; D017931:DNA Primers; C490287:GBP1 protein, human; D006023:Glycoproteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C102004:DDX17 protein, human; D019204:GTP-Binding Proteins; D053487:DEAD-box RNA Helicases; D020365:RNA Helicases; D007791:Lactoylglutathione Lyase