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. 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.
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. 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.
Authors: Constanze Hess; André Winkler; Alexandra K Lorenz; Vivien Holecska; Véronique Blanchard; Susanne Eiglmeier; Anna-Lena Schoen; Josephine Bitterling; Alexander D Stoehr; Dominique Petzold; Tim Schommartz; Maria M M Mertes; Carolin T Schoen; Ben Tiburzy; Anne Herrmann; Jörg Köhl; Rudolf A Manz; Michael P Madaio; Markus Berger; Hedda Wardemann; Marc Ehlers Journal: J Clin Invest Date: 2013-08-27 Impact factor: 14.808
Authors: Margaret E Ackerman; Max Crispin; Xiaojie Yu; Kavitha Baruah; Austin W Boesch; David J Harvey; Anne-Sophie Dugast; Erin L Heizen; Altan Ercan; Ickwon Choi; Hendrik Streeck; Peter A Nigrovic; Chris Bailey-Kellogg; Chris Scanlan; Galit Alter Journal: J Clin Invest Date: 2013-04-08 Impact factor: 14.808
Authors: Isabela Goeldner; Thelma L Skare; Shirley R Utiyama; Renato M Nisihara; Hoang van Tong; Iara J T Messias-Reason; Thirumalaisamy P Velavan Journal: PLoS One Date: 2014-04-21 Impact factor: 3.240