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


Journal

Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741

Informations de publication

Date de publication:
06 01 2020
Historique:
received: 18 06 2019
accepted: 23 12 2019
entrez: 8 1 2020
pubmed: 8 1 2020
medline: 15 5 2021
Statut: epublish

Résumé

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

Sections du résumé

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.

Identifiants

pubmed: 31907043
doi: 10.1186/s12967-019-02188-9
pii: 10.1186/s12967-019-02188-9
pmc: PMC6945416
doi:

Substances chimiques

Acute-Phase Proteins 0
Carrier Proteins 0
Membrane Glycoproteins 0
lipopolysaccharide-binding protein 0
Transcortin 9010-38-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

8

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Auteurs

Federica Ciregia (F)

Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, 4000, Liège, Belgium. federica.ciregia@uliege.be.

Dominique Baiwir (D)

GIGA Proteomic Facility, University of Liège, 4000, Liège, Belgium.

Gaël Cobraiville (G)

Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, 4000, Liège, Belgium.

Thibaut Dewael (T)

Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, 4000, Liège, Belgium.

Gabriel Mazzucchelli (G)

Mass Spectrometry Laboratory, System Biology and Chemical Biology, GIGA-Research, University of Liège, 4000, Liège, Belgium.

Valérie Badot (V)

Department of Rheumatology, CHU Brugmann, 1200, Brussels, Belgium.

Silvana Di Romana (S)

Department of Rheumatology, CHU Saint-Pierre, 1200, Brussels, Belgium.

Paschalis Sidiras (P)

Department of Rheumatology, Hôpital Erasme, Université Libre de Bruxelles, 1200, Brussels, Belgium.

Tatiana Sokolova (T)

Department of Rheumatology, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200, Brussels, Belgium.

Patrick Durez (P)

Department of Rheumatology, Cliniques Universitaires Saint-Luc, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, 1200, Brussels, Belgium.

Michel G Malaise (MG)

Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, 4000, Liège, Belgium.

Dominique de Seny (D)

Laboratory of Rheumatology, GIGA-I3, University of Liège, CHU de Liège, 4000, Liège, Belgium.

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