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The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis

Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their ca...

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Autores principales: Gyebrovszki, Balázs, Ács, András, Szabó, Dániel, Auer, Felícia, Novozánszki, Soma, Rojkovich, Bernadette, Magyar, Anna, Hudecz, Ferenc, Vékey, Károly, Drahos, László, Sármay, Gabriella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146365/
https://www.ncbi.nlm.nih.gov/pubmed/35628640
http://dx.doi.org/10.3390/ijms23105828
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author Gyebrovszki, Balázs
Ács, András
Szabó, Dániel
Auer, Felícia
Novozánszki, Soma
Rojkovich, Bernadette
Magyar, Anna
Hudecz, Ferenc
Vékey, Károly
Drahos, László
Sármay, Gabriella
author_facet Gyebrovszki, Balázs
Ács, András
Szabó, Dániel
Auer, Felícia
Novozánszki, Soma
Rojkovich, Bernadette
Magyar, Anna
Hudecz, Ferenc
Vékey, Károly
Drahos, László
Sármay, Gabriella
author_sort Gyebrovszki, Balázs
collection PubMed
description Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNFα production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)(2) fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to FcγR and to trigger TNFα release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylation and galactosylation levels of ACPA-IgG negatively correlate with inflammation-related parameters such as CRP, ESR, and RF. Functional assays show that dimerized ACPA-IgG significantly enhances TNFα release in an FcγRI-dependent manner, whereas healthy IgG does not. TNFα production inversely correlates with the relative intensities of the G0 glycoform, which lacks galactose and terminal sialic acid moieties.
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spelling pubmed-91463652022-05-29 The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis Gyebrovszki, Balázs Ács, András Szabó, Dániel Auer, Felícia Novozánszki, Soma Rojkovich, Bernadette Magyar, Anna Hudecz, Ferenc Vékey, Károly Drahos, László Sármay, Gabriella Int J Mol Sci Article Anti-citrullinated protein antibodies (ACPAs) are involved in the pathogenesis of rheumatoid arthritis. N-glycosylation pattern of ACPA-IgG and healthy IgG Fc differs. The aim of this study is to determine the relative sialylation and galactosylation level of ACPAs and control IgG to assess their capability of inducing TNFα production, and furthermore, to analyze the correlations between the composition of Fc glycans and inflammatory markers in RA. We isolated IgG from sera of healthy volunteers and RA patients, and purified ACPAs on a citrulline-peptide column. Immunocomplexes (IC) were formed by adding an F(ab)(2) fragment of anti-human IgG. U937 cells were used to monitor the binding of IC to FcγR and to trigger TNFα release determined by ELISA. To analyze glycan profiles, control IgG and ACPA-IgG were digested with trypsin and the glycosylation patterns of glycopeptides were analyzed by determining site-specific N-glycosylation using nano-UHPLC-MS/MS. We found that both sialylation and galactosylation levels of ACPA-IgG negatively correlate with inflammation-related parameters such as CRP, ESR, and RF. Functional assays show that dimerized ACPA-IgG significantly enhances TNFα release in an FcγRI-dependent manner, whereas healthy IgG does not. TNFα production inversely correlates with the relative intensities of the G0 glycoform, which lacks galactose and terminal sialic acid moieties. MDPI 2022-05-23 /pmc/articles/PMC9146365/ /pubmed/35628640 http://dx.doi.org/10.3390/ijms23105828 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gyebrovszki, Balázs
Ács, András
Szabó, Dániel
Auer, Felícia
Novozánszki, Soma
Rojkovich, Bernadette
Magyar, Anna
Hudecz, Ferenc
Vékey, Károly
Drahos, László
Sármay, Gabriella
The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title_full The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title_fullStr The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title_full_unstemmed The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title_short The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis
title_sort role of igg fc region n-glycosylation in the pathomechanism of rheumatoid arthritis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146365/
https://www.ncbi.nlm.nih.gov/pubmed/35628640
http://dx.doi.org/10.3390/ijms23105828
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