title: Peripheral blood gene expression and IgG glycosylation profiles as markers of tocilizumab treatment in rheumatoid arthritis.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Apoptosis and Genomics Research Group, Hungarian Academy of Sciences, Budapest, Hungary.
authors.forename: Bertalan
authors.initials: B
authors.lastname: Mesko
authors.forename: Szilard
authors.initials: S
authors.lastname: Poliska
authors.forename: Szilvia
authors.initials: S
authors.lastname: Szamosi
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szekanecz
authors.forename: Janos
authors.initials: J
authors.lastname: Podani
authors.forename: Csaba
authors.initials: C
authors.lastname: Varadi
authors.forename: Andras
authors.initials: A
authors.lastname: Guttman
authors.forename: Laszlo
authors.initials: L
authors.lastname: Nagy
mesh_terms: D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D059467:Transcriptome / Q000276:immunology*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D005819:Genetic Markers; D007074:Immunoglobulin G; C502936:tocilizumab