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.

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.

Print Article Summary Cat 2 CME Report