Research article

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia

Thierry Lequerré^1* , Carine Bansard^2* , Olivier Vittecoq¹ , Céline Derambure¹ , Martine Hiron² , Maryvonne Daveau² , François Tron² , Xavier Ayral³ , Norman Biga⁴ , Isabelle Auquit-Auckbur⁵ , Gilles Chiocchia⁶ , Xavier Le Loët¹ and Jean-Philippe Salier^{2^}

¹  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, and Consortium EGERIE, France

²  Inserm Unité 905, Institut Fédératif de Recherche Multidisciplinaire sur les Peptides 23, Institute for Biomedical Research, University of Rouen, Faculté de Médecine-Pharmacie, Rouen, France

³  Department of Rheumatology, Cochin Hospital, AP-HP, University of Paris-Descartes, 27, rue du faubourg Saint-Jacques, 75679 Paris Cedex 14, France

⁴  Department of Orthopedic and Traumatology, Rouen University Hospital, 76031 Rouen Cedex, France

⁵  Department of Plastic and Reconstructive Surgery, Rouen University Hospital, 76031 Rouen Cedex, France

⁶  Institut Cochin, Université Paris Descartes, Inserm (U567), CNRS (UMR8104), Paris, and Consortium EGERIE, France

author email corresponding author email^Deceased * Contributed equally

Arthritis Research & Therapy 2009, 11:R99doi:10.1186/ar2744

Published:	29 June 2009

Abstract

Introduction

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.