RT Journal Article
SR Electronic
T1 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
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1524
OP 1532
DO 10.3899/jrheum.120092
VO 39
IS 8
A1 RENÊ DONIZETI RIBEIRO OLIVEIRA
A1 VANESSA FONTANA
A1 CRISTINA MORAES JUNTA
A1 MÁRCIA MARIA CHIQUITELLI MARQUES
A1 CLÁUDIA MACEDO
A1 DIANE MEYRE RASSI
A1 GERALDO ALEIXO PASSOS
A1 EDUARDO ANTONIO DONADI
A1 PAULO LOUZADA-JUNIOR
YR 2012
UL http://www.jrheum.org/content/39/8/1524.abstract
AB Objective. We aimed to evaluate whether the differential gene expression profiles of patients with rheumatoid arthritis (RA) could distinguish responders from nonresponders to methotrexate (MTX) and, in the case of MTX nonresponders, responsiveness to MTX plus anti-tumor necrosis factor-α (anti-TNF) combined therapy. Methods. We 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. Results. 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 non-responders, the CCL4, CD83, and BCL2A1 genes were induced in relation to responders. Conclusion. Study of the gene expression profiles of RA peripheral blood cells permitted differentiation of responders from nonresponders to MTX and anti-TNF. Several candidate genes in MTX non-responders (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.