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Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis.
Journal of Translational Medicine ( IF 6.1 ) Pub Date : 2020-01-06 , DOI: 10.1186/s12967-019-02188-9
Federica Ciregia 1 , Dominique Baiwir 2 , Gaël Cobraiville 1 , Thibaut Dewael 1 , Gabriel Mazzucchelli 3 , Valérie Badot 4 , Silvana Di Romana 5 , Paschalis Sidiras 6 , Tatiana Sokolova 7 , Patrick Durez 7 , Michel G Malaise 1 , Dominique de Seny 1
Affiliation  

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. 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.

中文翻译:

脂多糖结合蛋白和皮质类固醇结合球蛋白的糖基化缺乏与类风湿关节炎的活性和对治疗的反应有关。

背景技术血清蛋白糖基化是炎性关节炎疾病如类风湿关节炎(RA)的研究领域。实际上,一些研究强调了RA中蛋白质糖基化的异常。考虑到多种类型的酶,单糖和糖苷键,糖基化是翻译后修饰中最复杂的一种。通过这项工作,我们开始了对RA患者和对照组血清中糖蛋白的初步筛选。方法为了从血清中分离糖蛋白,使用凝集素小麦胚芽凝集素,并通过LC-MS / MS研究患者与对照组之间的定量差异。因此,我们将注意力集中在这个探索阶段发现的两种糖蛋白:皮质类固醇结合球蛋白(CBG)和脂多糖结合蛋白(LBP)。随后通过免疫测定法进行的验证扩大到了更多的早期RA(ERA)患者(n = 90)和匹配良好的健康对照(n = 90)。结果我们观察到与健康对照组相比,ERA患者的CBG和LBP糖基化显着降低。此外,在治疗12个月后,糖基化的CBG和LBP水平均增加到与对照相当的值。另外,这些变化与临床参数相关。结论这项研究能够观察到CBG和LBP的糖基化变化与RA疾病活性及其对治疗的反应有关。结果我们观察到与健康对照组相比,ERA患者的CBG和LBP糖基化显着降低。此外,在治疗12个月后,糖基化的CBG和LBP水平均增加到与对照相当的值。另外,这些变化与临床参数相关。结论这项研究能够观察到CBG和LBP的糖基化变化与RA疾病活性及其对治疗的反应有关。结果我们观察到与健康对照组相比,ERA患者的CBG和LBP糖基化显着降低。此外,在治疗12个月后,糖基化的CBG和LBP水平均增加到与对照相当的值。另外,这些变化与临床参数相关。结论这项研究能够观察到CBG和LBP的糖基化变化与RA疾病活性及其对治疗的反应有关。
更新日期:2020-01-07
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