Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia.
BACKGROUND
Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia.


METHODS
Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions). Extracted mRNAs were used for large-scale gene-expression profiling. The different gene-expression combinations identified by comparison of profiles of early, LS RA and healthy synovia were linked to the biological processes involved in each situation.


RESULTS
Three combinations of 719, 116 and 52 transcripts discriminated, respectively, early from LS RA, and early or LS RA from healthy synovia. We identified several gene clusters and distinct molecular signatures specifically expressed during early or LS RA, thereby suggesting the involvement of different pathophysiological mechanisms during the course of RA.


CONCLUSIONS
Early and LS RA have distinct molecular signatures with different biological processes participating at different times during the course of the disease. These results suggest that better knowledge of the main biological processes involved at a given RA stage might help to choose the most appropriate treatment.
Lequerré
Thierry
T
Department of Rheumatology, Rouen University Hospital and Inserm 905 & Institut Fédératif de Recherche Multidisciplinaire sur les Peptides 23, Institute for Biomedical Research, University of Rouen, 76031 Rouen Cedex, France. thierry.lequerre@chu-rouen.fr
Bansard
Carine
C
Vittecoq
Olivier
O
Derambure
Céline
C
Hiron
Martine
M
Daveau
Maryvonne
M
Tron
François
F
Ayral
Xavier
X
Biga
Norman
N
Auquit-Auckbur
Isabelle
I
Chiocchia
Gilles
G
Le Loët
Xavier
X
Salier
Jean-Philippe
JP
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D008875:Middle Aged; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
D005819:Genetic Markers