Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

脂多糖结合蛋白和皮质类固醇结合球蛋白的糖基化缺陷与类风湿关节炎的活动性和治疗反应有关

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作者:Federica Ciregia, Dominique Baiwir, Gaël Cobraiville, Thibaut Dewael, Gabriel Mazzucchelli, Valérie Badot, Silvana Di Romana, Paschalis Sidiras, Tatiana Sokolova, Patrick Durez, Michel G Malaise, Dominique de Seny

Background

Serum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls.

Conclusions

This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

Methods

In order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC-MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90).

Results

We observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters. Conclusions: This study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

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