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

At a given time, rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms is still poorly understood. Because previous microarrays studies have only focused on late RA stages, we aimed to compare the biological and molecular profiles in early and long-standing (LS) RA. Synovial biopsies obtained by arthroscopy were performed in 4 early untreated RA patients, 4 LS treated RA patients and 7 control patients. Extracted mRNA were linearly amplified and used for large-scale gene expression profiling by cDNA arrays. By gene ontology analysis, the different gene combinations obtained by comparison of early, LS RA and normal synovium were used to identify the biological processes, molecular functions and pathways involved at each stage. Three combinations of 719, 116 and 52 transcripts dissociated respectively early from LS RA patients, early or LS RA from normal synovium. We identified several gene clusters and distinct molecular signatures specifically related to early or LS RA suggesting the involvement of different pathological mechanisms at each stage. Early and LS RA have distinct molecular signatures with the participation of different biological processes during the course of the disease. These results suggest that a better knowledge of the main biological processes involved at a given RA stage might help the rheumatologist to choose the more appropriate treatment. PBMC then RNA were extracted from synovial biopsies of 4 eraly RA patients, 4 long-standing RA patients and from 7 normal synovium used as control. Each sample was hybridized three times in different nylon membrane.