Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy
Symptoms of rheumatoid arthritis (RA) improve during pregnancy, a phenomenon that was found to be associated with N-glycosylation changes of immunoglobulin G. Recent advances in high-throughput glycosylation analysis allow the assessment of the N-glycome of human sera as well. The aim of this study...
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doaj-ed669ab5762d45babcf68443b6306e022020-11-24T23:58:10ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2018-01-01410.3389/fmed.2017.00241319358Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after PregnancyKarli R. Reiding0Gerda C. M. Vreeker1Albert Bondt2Albert Bondt3Marco R. Bladergroen4Johanna M. W. Hazes5Yuri E. M. van der Burgt6Yuri E. M. van der Burgt7Manfred Wuhrer8Radboud J. E. M. Dolhain9Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Rheumatology, Leiden University Medical Center, Leiden, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Rheumatology, Erasmus Medical Center, Rotterdam, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Clinical Chemistry, Leiden University Medical Center, Leiden, NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, NetherlandsDepartment of Rheumatology, Erasmus Medical Center, Rotterdam, NetherlandsSymptoms of rheumatoid arthritis (RA) improve during pregnancy, a phenomenon that was found to be associated with N-glycosylation changes of immunoglobulin G. Recent advances in high-throughput glycosylation analysis allow the assessment of the N-glycome of human sera as well. The aim of this study was to identify new protein N-glycosylation properties that associate with changes in RA disease activity during and after pregnancy. A longitudinal cohort of serum samples was collected during 285 pregnancies (32 control individuals and 253 RA patients). Per individual one sample was collected before conception, three during pregnancy, and three after delivery. Released serum protein N-glycans were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after employing chemical modification of the sialic acids to allow discrimination of sialic acid linkage isomers. Serum protein N-glycosylation showed strongly modified during pregnancy, with similar changes visible in control individuals and RA pregnancies. Namely, a decrease in bisection and an increase in galactosylation in diantennary glycans were found, as well as an increase in tri- and tetraantennary species and α2,3-linked sialylation thereof. The change in RA disease activity [DAS28(3)-CRP] proved negatively associated with the galactosylation of diantennary N-glycans, and positively with the sialylation of triantennary fucosylated species (A3FGS). While the protein source of the novel finding A3FGS is thus far unknown, its further study may improve our understanding of the etiology of RA disease severity.http://journal.frontiersin.org/article/10.3389/fmed.2017.00241/fullrheumatoid arthritispregnancydisease activity score 28 C-reactive proteinglycosylationtotal serum protein N-glycosylationethyl esterification matrix-assisted laser desorption/ionization time-of-flight mass spectrometry |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Karli R. Reiding Gerda C. M. Vreeker Albert Bondt Albert Bondt Marco R. Bladergroen Johanna M. W. Hazes Yuri E. M. van der Burgt Yuri E. M. van der Burgt Manfred Wuhrer Radboud J. E. M. Dolhain |
spellingShingle |
Karli R. Reiding Gerda C. M. Vreeker Albert Bondt Albert Bondt Marco R. Bladergroen Johanna M. W. Hazes Yuri E. M. van der Burgt Yuri E. M. van der Burgt Manfred Wuhrer Radboud J. E. M. Dolhain Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy Frontiers in Medicine rheumatoid arthritis pregnancy disease activity score 28 C-reactive protein glycosylation total serum protein N-glycosylation ethyl esterification matrix-assisted laser desorption/ionization time-of-flight mass spectrometry |
author_facet |
Karli R. Reiding Gerda C. M. Vreeker Albert Bondt Albert Bondt Marco R. Bladergroen Johanna M. W. Hazes Yuri E. M. van der Burgt Yuri E. M. van der Burgt Manfred Wuhrer Radboud J. E. M. Dolhain |
author_sort |
Karli R. Reiding |
title |
Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy |
title_short |
Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy |
title_full |
Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy |
title_fullStr |
Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy |
title_full_unstemmed |
Serum Protein N-Glycosylation Changes with Rheumatoid Arthritis Disease Activity during and after Pregnancy |
title_sort |
serum protein n-glycosylation changes with rheumatoid arthritis disease activity during and after pregnancy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Medicine |
issn |
2296-858X |
publishDate |
2018-01-01 |
description |
Symptoms of rheumatoid arthritis (RA) improve during pregnancy, a phenomenon that was found to be associated with N-glycosylation changes of immunoglobulin G. Recent advances in high-throughput glycosylation analysis allow the assessment of the N-glycome of human sera as well. The aim of this study was to identify new protein N-glycosylation properties that associate with changes in RA disease activity during and after pregnancy. A longitudinal cohort of serum samples was collected during 285 pregnancies (32 control individuals and 253 RA patients). Per individual one sample was collected before conception, three during pregnancy, and three after delivery. Released serum protein N-glycans were measured by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) after employing chemical modification of the sialic acids to allow discrimination of sialic acid linkage isomers. Serum protein N-glycosylation showed strongly modified during pregnancy, with similar changes visible in control individuals and RA pregnancies. Namely, a decrease in bisection and an increase in galactosylation in diantennary glycans were found, as well as an increase in tri- and tetraantennary species and α2,3-linked sialylation thereof. The change in RA disease activity [DAS28(3)-CRP] proved negatively associated with the galactosylation of diantennary N-glycans, and positively with the sialylation of triantennary fucosylated species (A3FGS). While the protein source of the novel finding A3FGS is thus far unknown, its further study may improve our understanding of the etiology of RA disease severity. |
topic |
rheumatoid arthritis pregnancy disease activity score 28 C-reactive protein glycosylation total serum protein N-glycosylation ethyl esterification matrix-assisted laser desorption/ionization time-of-flight mass spectrometry |
url |
http://journal.frontiersin.org/article/10.3389/fmed.2017.00241/full |
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