PT  - JOURNAL ARTICLE
AU  - BERTALAN MESKO
AU  - SZILARD POLISKA
AU  - SZILVIA SZAMOSI
AU  - ZOLTAN SZEKANECZ
AU  - JANOS PODANI
AU  - CSABA VARADI
AU  - ANDRAS GUTTMAN
AU  - LASZLO NAGY
TI  - Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis
AID  - 10.3899/jrheum.110961
DP  - 2012 May 01
TA  - The Journal of Rheumatology
PG  - 916--928
VI  - 39
IP  - 5
4099  - http://www.jrheum.org/content/39/5/916.short
4100  - http://www.jrheum.org/content/39/5/916.full
SO  - J Rheumatol2012 May 01; 39
AB  - Objective. Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment. Methods. Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders. Results. Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline. Conclusion. As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.