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

Lequerré, Thierry; Bansard, Carine; Vittecoq, Olivier; Derambure, Céline; Hiron, Martine; Daveau, Maryvonne; Tron, François; Ayral, X.; Biga, N.; Auquit-Auckbur, I.; Chiocchia, Gilles; Loët, Xavier Le; Salier, Jean‐Philippe

doi:10.1186/ar2744

Cited by 42 publications

(36 citation statements)

References 19 publications

(16 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…TNF-␣ therapy also affected the expression of four other genes, selectin P (SELP), lysosomal-associated membrane protein 1 (LAMP1), ferritin heavy polypeptide 1 (FTH1), and vestigial like 4 (VGLL4), found deregulated in PBMCs and in synovia from RA patients (6,7,11,26,41). An increase in the levels of SELP and FTH1 has been detected in synovial fluid from RA (19,33).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-α treatments

Meugnier

Coury

Tébib

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

The efficacy of anti-TNF-α therapies highlights the role of TNF-α in the pathogenesis of rheumatoid arthritis (RA). However, the mechanism of action of these agents is poorly understood at the molecular level. The aim of this study was to characterize the effects of anti-TNF-α treatment on the global gene expression profile in peripheral blood mononuclear cells (PBMCs) of responder RA patients. Changes in gene expression were determined using oligonucleotide microarrays (25,341 genes) in PBMCs obtained before and after 12 wk of treatment with either etanercept or adalimumab from responder RA patients. Two hundred fifty-one genes displayed significant changes (false discovery rate < 0.1%) in expression level (178 upregulations with mean fold change = 1.5 and 73 downregulations with mean fold change = -1.50) after 12 wk of treatment. Importantly, the expression of several genes, including those coding for the calcium binding proteins S100A12 and A8, CD14 antigen, Selectin P, or ribosomal protein L39, reported to be upregulated in RA patients, were found to be decreased after anti-TNF-α treatment. Globally, inflammation, immune response, apoptosis, protein synthesis, and mitochondrial oxido-reduction were the most affected pathways in response to anti-TNF-α treatment. The obtained gene expression signature in PBMCs provides new information to better understand the mechanisms of action of anti-TNF-α treatment in RA patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-α treatments

Meugnier

Coury

Tébib

et al. 2011

Physiological Genomics

View full text Add to dashboard Cite

show abstract

“…More interestingly, the activation of the STAT-1 pathway was demonstrated by analyzing the expression of immuneregulated genes in the synovial tissue of RA and OA patients (16,70). In other studies gene expression profiles are compared by applying synovial tissues from RA patients, which differ in treatment (anti-TNF treatment, infliximab) (45,71) or in disease stage (early vs. long-standing RA) (44,64). Although these reports are very valuable, they provide a rather limited picture of RA pathogenesis, since they rely on the analysis of isolated cell types (e.g., peripheral blood lymphocytes, cultured fibroblasts) and/or on a limited number of genes.…”

mentioning

confidence: 99%

Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis

Ungethuem

Haeupl

Witt

et al. 2010

Physiological Genomics

114

View full text Add to dashboard Cite

show abstract

“…97 With respect to disease expression, microarray studies of synovial biopsies compared expression of early and long standing rheumatoid arthritis. 98 In that study, the authors identified several gene clusters and distinct molecular signatures specifically expressed during early or late RA, suggesting that different mechanisms are in play at various stages of RA.…”

Section: Gene Expression Studies In Ramentioning

confidence: 93%

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

O’Rielly

Rahman

2010

PGPM

View full text Add to dashboard Cite

Rheumatoid arthritis (RA) is a chronic heterogeneous autoimmune disorder of unknown etiology resulting in inflammation in the synovium, cartilage, and bone. Genetic factors play an important role in susceptibility to RA as the heritability of RA is between 50% and 60%, with the human leukocyte antigen (HLA) locus accounting for at least 30% of overall genetic risk. Outside the major histocompatibility complex (MHC) region, six additional risk loci have been identified and validated including PTPN22, STAT4, PADI4, CTLA4, TNFAIP3-OLIG3, and TRAF1/C5. Genetic factors are also important in RA pharmacotherapy due to the gene-dependent activity of enzymes involved in the pharmacokinetics and/or pharmacodynamics of RA medications. Indeed, there is great variability in drug efficacy as well as adverse events associated with any anti-rheumatic therapy and genetics is thought to contribute significantly to this inter-individual variability in response. This review will summarize the genetic factors that have been implicated in the pathogenesis of RA, and how these determinants may factor into the potential pharmacogenetics of this disease. We will also review the therapeutic agents that are currently being utilized or presently being evaluated in the treatment of RA, along with potential pharmacogenetic markers that have been proposed for such medications.

show abstract

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

Cited by 42 publications

References 19 publications

Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-α treatments

Gene expression profiling in peripheral blood cells of patients with rheumatoid arthritis in response to anti-TNF-α treatments

Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis

Pharmacogenetics of rheumatoid arthritis: Potential targets from susceptibility genes and present therapies

Contact Info

Product

Resources

About