TY - JOUR
T1 - IgG glycosylation changes and MBL2 polymorphisms
T2 - associations with markers of systemic inflammation and joint destruction in rheumatoid arthritis
AU - Troelsen, Lone N
AU - Jacobsen, Søren
AU - Abrahams, Jodie L
AU - Royle, Louise
AU - Rudd, Pauline M
AU - Narvestad, Eva
AU - Heegaard, Niels Henrik Helweg
AU - Garred, Peter
PY - 2012/3
Y1 - 2012/3
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 < 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. The Journal of Rheumatology
AB - 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. The Journal of Rheumatology
U2 - 10.3899/jrheum.110584
DO - 10.3899/jrheum.110584
M3 - Journal article
C2 - 22247351
SN - 0315-162X
VL - 39
SP - 463
EP - 469
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 3
ER -