Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis
The Journal of Rheumatology, 04/02/2012
Mesko B et al. – As a preliminary report, gene expression changes as a result of tocilizumab therapy in rheumatoid arthritis (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.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 Nglycan 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.
- 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.