title: Hypogalactosylation of serum N-glycans fails to predict clinical response to methotrexate and TNF inhibition in rheumatoid arthritis.
abstract: BACKGROUND
  Rheumatoid arthritis (RA) is associated with hypogalactosylation of immunoglobulin G (IgG). We examined whether a proxy measure for galactosylation of IgG N-glycans could predict response to therapy or was differentially affected by methotrexate (MTX) or TNF blockade.
  
  
  METHODS
  Using a previously defined normal phase high-performance liquid chromatography approach, we ascertained the galactosylation status of whole serum N-glycans in two well-defined RA clinical cohorts: the Autoimmune Biomarkers Collaborative Network (n = 98) and Nested I (n = 64). The ratio of agalactosylated to monogalactosylated N-glycans in serum (sG0/G1) was determined before and during therapy with MTX or TNF inhibition and correlated with anticitrullinated peptide antibody (ACPA) status and clinical response as assessed by 28-joint Disease Activity Score utilizing C-reactive peptide and European League Against Rheumatism response criteria.
  
  
  RESULTS
  RA patients from both cohorts exhibited elevation of sG0/G1 at baseline. Improvement in clinical scores correlated with a reduction in sG0/G1 (Spearman's ρ = 0.31 to 0.37; P < 0.05 for each cohort). However, pretreatment sG0/G1 was not predictive of clinical response. Changes in sG0/G1 were similar in the MTX and TNF inhibitor groups. Corrected for disease activity, ACPA positivity correlated with higher sG0/G1.
  
  
  CONCLUSIONS
  Baseline serum N-glycan hypogalactosylation, an index previously correlated with hypogalactosylation of IgG N-glycans, did not distinguish patients with rheumatoid arthritis who were likely to experience a favorable clinical response to MTX or TNF blockade. Clinical improvement was associated with partial glycan normalization. ACPA-positive patients demonstrated enhanced N-glycan aberrancy compared with ACPA-negative patients.
authors.affiliation: Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, One Jimmy Fund Way, Smith 516c, Boston, MA 02115 USA. .
authors.forename: Altan
authors.initials: A
authors.lastname: Ercan
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hazen
authors.forename: Franak
authors.initials: F
authors.lastname: Batliwalla
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Coblyn
authors.forename: Nancy
authors.initials: N
authors.lastname: Shadick
authors.forename: Michael E
authors.initials: ME
authors.lastname: Weinblatt
authors.forename: Peter
authors.initials: P
authors.lastname: Gregersen
authors.forename: David M
authors.initials: DM
authors.lastname: Lee
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy; D015331:Cohort Studies; D005260:Female; D005690:Galactose / Q000097:blood*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood*; D011237:Predictive Value of Tests; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D007074:Immunoglobulin G; D011134:Polysaccharides; D014409:Tumor Necrosis Factor-alpha; D005690:Galactose; D008727:Methotrexate