title: IgG glycosylation changes and MBL2 polymorphisms: associations with markers of systemic inflammation and joint destruction in rheumatoid arthritis.
abstract: OBJECTIVE
  To examine whether IgG glycosylation changes and MBL2 genotypes are associated with systemic inflammation and joint destruction in rheumatoid arthritis (RA).
  
  
  METHODS
  IgG N-glycan content was determined from serum in 118 patients with RA by high-throughput glycan analysis using normal-phase high-pressure liquid chromatography. MBL2 extended genotypes (YA/YA, YA/XA, XA/XA, YA/YO, XA/YO, YO/YO) were determined. Systemic inflammation was assessed by serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α). Joint destruction was assessed by total Sharp score (TSS) and alloplastic surgery records.
  
  
  RESULTS
  IgG hypogalactosylation was significantly correlated to IL-6 (Spearman's rho = 0.32, p < 0.001), CRP (Spearman's rho = 0.31, p < 0.001), TSS (Spearman's rho = 0.25, p = 0.01), and alloplastic replacement of joints (Spearman's rho = 0.18, p = 0.05). In multivariate analysis including age, CRP, anticitrullinated protein antibodies (ACPA), and other confounders, IgG hypogalactosylation was significantly associated with TSS (p = 0.014) and alloplastic joint replacement (OR 76.5, p = 0.041) in patients homozygous for the high expression MBL2 genotype YA/YA, but not in carriers of lower expression genotypes.
  
  
  CONCLUSIONS
  Decreased galactosylation of IgG correlated to markers of inflammation, i.e., IL-6 and CRP. Only in patients homozygous for high expression of the MBL2 genotype YA/YA was IgG hypogalactosylation associated with markers of joint destruction. Our results suggest that inflammation-associated decreased galactosylation of IgG combined with high expression MBL2 genotypes are involved in the pathophysiology of RA.
authors.affiliation: Department of Rheumatology, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. lone.troelsen@mail.dk
authors.forename: Lone N
authors.initials: LN
authors.lastname: Troelsen
authors.forename: Søren
authors.initials: S
authors.lastname: Jacobsen
authors.forename: Jodie L
authors.initials: JL
authors.lastname: Abrahams
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
authors.forename: Eva
authors.initials: E
authors.lastname: Narvestad
authors.forename: Niels H
authors.initials: NH
authors.lastname: Heegaard
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000503:physiopathology; D015850:Interleukin-6 / Q000097:blood*; D007596:Joints / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D006023:Glycoproteins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D007074:Immunoglobulin G; D015850:Interleukin-6; D037601:Mannose-Binding Lectin; D014409:Tumor Necrosis Factor-alpha; C445619:MBL2 protein, human; C046179:glycosylated IgG; D006023:Glycoproteins