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IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples
OBJECTIVE: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti–citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N‐linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wiley Periodicals, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544857/ https://www.ncbi.nlm.nih.gov/pubmed/35188715 http://dx.doi.org/10.1002/art.42098 |
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author | Kissel, Theresa Hafkenscheid, Lise Wesemael, Tineke J. Tamai, Mami Kawashiri, Shin‐ya Kawakami, Atsushi El‐Gabalawy, Hani S. van Schaardenburg, Dirkjan Rantapää‐Dahlqvist, Solbritt Wuhrer, Manfred van der Helm‐van Mil, Annette H. M. Allaart, Cornelia F. van der Woude, Diane Scherer, Hans U. Toes, Rene E. M. Huizinga, Tom W. J. |
author_facet | Kissel, Theresa Hafkenscheid, Lise Wesemael, Tineke J. Tamai, Mami Kawashiri, Shin‐ya Kawakami, Atsushi El‐Gabalawy, Hani S. van Schaardenburg, Dirkjan Rantapää‐Dahlqvist, Solbritt Wuhrer, Manfred van der Helm‐van Mil, Annette H. M. Allaart, Cornelia F. van der Woude, Diane Scherer, Hans U. Toes, Rene E. M. Huizinga, Tom W. J. |
author_sort | Kissel, Theresa |
collection | PubMed |
description | OBJECTIVE: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti–citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N‐linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. METHODS: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new‐onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long‐term drug‐free remission (DFR) during up to 16 years follow‐up. RESULTS: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. CONCLUSION: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre‐disease phase and contributes to disease development. |
format | Online Article Text |
id | pubmed-9544857 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wiley Periodicals, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95448572022-10-14 IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples Kissel, Theresa Hafkenscheid, Lise Wesemael, Tineke J. Tamai, Mami Kawashiri, Shin‐ya Kawakami, Atsushi El‐Gabalawy, Hani S. van Schaardenburg, Dirkjan Rantapää‐Dahlqvist, Solbritt Wuhrer, Manfred van der Helm‐van Mil, Annette H. M. Allaart, Cornelia F. van der Woude, Diane Scherer, Hans U. Toes, Rene E. M. Huizinga, Tom W. J. Arthritis Rheumatol Rheumatoid Arthritis OBJECTIVE: The autoimmune response in rheumatoid arthritis (RA) is marked by the presence of anti–citrullinated protein antibodies (ACPAs). A notable feature of IgG ACPA is the abundant expression of N‐linked glycans in the variable domain. However, the presence of ACPA variable domain glycosylation (VDG) across disease stages, and its response to therapy, are poorly described. To understand its dynamics, we investigated the abundance of IgG ACPA VDG in 1,498 samples from individuals in different clinical stages. METHODS: Using liquid chromatography, we analyzed IgG ACPA VDG profiles in 7 different cohorts from Japan, Canada, The Netherlands, and Sweden. We assessed 106 healthy individuals, 228 individuals with presymptomatic RA, 277 individuals with arthralgia, 307 patients with new‐onset/early RA, and 117 RA patients after prespecified treatment regimens. Additionally, we measured VDG in 234 samples from patients with RA who did or did not achieve long‐term drug‐free remission (DFR) during up to 16 years follow‐up. RESULTS: IgG ACPA VDG significantly increased (P < 0.0001) toward disease onset and was associated with ACPA levels and epitope spreading prior to diagnosis. A slight increase in VDG was observed in patients with established RA, with a moderate influence of treatment (P = 0.007). In patients in whom DFR was later achieved, IgG ACPA VDG was already reduced at the time of RA onset. CONCLUSION: The abundance of IgG ACPA VDG increases toward RA onset and correlates with maturation of the ACPA response. While IgG ACPA VDG levels are fairly stable in established disease, a lower degree of VDG at RA onset correlates with DFR. Although the underlying biologic mechanisms remain elusive, our data support the concept that VDG relates to an expansion of the ACPA response in the pre‐disease phase and contributes to disease development. Wiley Periodicals, Inc. 2022-05-28 2022-07 /pmc/articles/PMC9544857/ /pubmed/35188715 http://dx.doi.org/10.1002/art.42098 Text en © 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Rheumatoid Arthritis Kissel, Theresa Hafkenscheid, Lise Wesemael, Tineke J. Tamai, Mami Kawashiri, Shin‐ya Kawakami, Atsushi El‐Gabalawy, Hani S. van Schaardenburg, Dirkjan Rantapää‐Dahlqvist, Solbritt Wuhrer, Manfred van der Helm‐van Mil, Annette H. M. Allaart, Cornelia F. van der Woude, Diane Scherer, Hans U. Toes, Rene E. M. Huizinga, Tom W. J. IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title | IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title_full | IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title_fullStr | IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title_full_unstemmed | IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title_short | IgG Anti–Citrullinated Protein Antibody Variable Domain Glycosylation Increases Before the Onset of Rheumatoid Arthritis and Stabilizes Thereafter: A Cross‐Sectional Study Encompassing ~1,500 Samples |
title_sort | igg anti–citrullinated protein antibody variable domain glycosylation increases before the onset of rheumatoid arthritis and stabilizes thereafter: a cross‐sectional study encompassing ~1,500 samples |
topic | Rheumatoid Arthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9544857/ https://www.ncbi.nlm.nih.gov/pubmed/35188715 http://dx.doi.org/10.1002/art.42098 |
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