Differential Gene Expression Profiles May Differentiate Responder and Nonresponder Patients with Rheumatoid Arthritis for Methotrexate (MTX) Monotherapy and MTX plus Tumor Necrosis Factor Inhibitor Combined Therapy
The Journal of Rheumatology, 07/05/2012
Oliveira RDR et al. – Study of the gene expression profiles of rheumatoid arthritis (RA) peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti–TNF. Several candidate genes in MTX nonresponders (CCL4, HTRA2, PRKCD, BCL2A1, CAV1, TNIP1, CASP8AP2, MXD1, and BTG2) and 3 genes in MTX plus anti–TNF nonresponders (CCL4, CD83, and BCL2A1) were identified for further study.Methods
- The authors evaluated 25 patients with RA taking MTX 15–20 mg/week as a monotherapy (8 responders and 17 nonresponders).
- All MTX nonresponders received infliximab and were reassessed after 20 weeks to evaluate their anti–TNF responsiveness using the European League Against Rheumatism response criteria.
- A differential gene expression analysis from peripheral blood mononuclear cells was performed in terms of hierarchical gene clustering, and an evaluation of differentially expressed genes was performed using the significance analysis of microarrays program.
- Hierarchical gene expression clustering discriminated MTX responders from nonresponders, and MTX plus anti–TNF responders from nonresponders.
- The evaluation of only highly modulated genes (fold change > 1.3 or < 0.7) yielded 5 induced (4 antiapoptotic and CCL4) and 4 repressed (4 proapoptotic) genes in MTX nonresponders compared to responders.
- In MTX plus anti–TNF nonresponders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders.