TY - JOUR T1 - IgG Glycosylation Changes and <em>MBL2</em> Polymorphisms: Associations with Markers of Systemic Inflammation and Joint Destruction in Rheumatoid Arthritis JF - The Journal of Rheumatology JO - J Rheumatol SP - 463 LP - 469 DO - 10.3899/jrheum.110584 VL - 39 IS - 3 AU - LONE N. TROELSEN AU - SØREN JACOBSEN AU - JODIE L. ABRAHAMS AU - LOUISE ROYLE AU - PAULINE M. RUDD AU - EVA NARVESTAD AU - NIELS H. HEEGAARD AU - PETER GARRED Y1 - 2012/03/01 UR - http://www.jrheum.org/content/39/3/463.abstract N2 - 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 &lt; 0.001), CRP (Spearman’s rho = 0.31, p &lt; 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. Conclusion. 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. ER -