Cargando…
The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis
OBJECTIVES: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrulli...
Autores principales: | , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234203/ https://www.ncbi.nlm.nih.gov/pubmed/36255271 http://dx.doi.org/10.1093/rheumatology/keac601 |
_version_ | 1785052434013356032 |
---|---|
author | Westerlind, Helga Kastbom, Alf Rönnelid, Johan Hansson, Monika Alfredsson, Lars Mathsson-Alm, Linda Serre, Guy Cornillet, Martin Holmdahl, Rikard Skriner, Karl Bang, Holger Klareskog, Lars Saevarsdottir, Saedis Lundberg, Karin Grönwall, Caroline Askling, Johan |
author_facet | Westerlind, Helga Kastbom, Alf Rönnelid, Johan Hansson, Monika Alfredsson, Lars Mathsson-Alm, Linda Serre, Guy Cornillet, Martin Holmdahl, Rikard Skriner, Karl Bang, Holger Klareskog, Lars Saevarsdottir, Saedis Lundberg, Karin Grönwall, Caroline Askling, Johan |
author_sort | Westerlind, Helga |
collection | PubMed |
description | OBJECTIVES: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. METHODS: A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. RESULTS: During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. CONCLUSION: Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk. |
format | Online Article Text |
id | pubmed-10234203 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-102342032023-06-02 The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis Westerlind, Helga Kastbom, Alf Rönnelid, Johan Hansson, Monika Alfredsson, Lars Mathsson-Alm, Linda Serre, Guy Cornillet, Martin Holmdahl, Rikard Skriner, Karl Bang, Holger Klareskog, Lars Saevarsdottir, Saedis Lundberg, Karin Grönwall, Caroline Askling, Johan Rheumatology (Oxford) Clinical Science OBJECTIVES: To assess the association between venous thromboembolic (VTE) events and autoantibodies, following patients from RA diagnosis, measuring occurrence, levels and collective load of different autoantibodies against post-translational protein modifications, in particular recognizing citrullination (e.g. citrullinated fibrinogen) and RF by isotype. METHODS: A cohort of 2814 patients with newly diagnosed RA were followed for incident VTE through register linkages. Sera from RA diagnosis were centrally analysed for antibodies to second generation cyclic citrullinated peptides (anti-CCP2), 20 anti-citrullinated protein antibody (ACPA) fine-specificities, antibodies to additional protein modifications (carbamylation and acetylation) and RF by isotype. Association between baseline serology status and future VTE was analysed using Cox regression adjusted for age, sex and calendar period of RA diagnosis, overall and stratified by anti-CCP2 and RF positivity. RESULTS: During a median 16 years of follow-up, 213 first-ever VTE events were registered (5.0/1000 person-years). IgG anti-CCP2 (present in 65% of cohort) associated with VTE (hazard ratio [HR] = 1.33, 95% CI: 1.00, 1.78), in a dose-response manner. The risk of VTE increased with number of ACPA fine-specificities. IgM RF, but no other RF isotypes, associated with VTE (HR = 1.38, 95% CI: 1.04, 1.82). The associations were independent from smoking and HLA-DRB1 shared epitope alleles. None of the carbamylated or acetylated antibody reactivities associated with VTE. CONCLUSION: Anti-CCP2, load of ACPA fine-specificities and IgM RF at RA diagnosis are associated with an increased risk of future VTE in RA. Antibodies to citrullinated fibrinogen did not differ substantially from other ACPA fine-specificities. Autoreactivity to other post-translational modifications was not associated with VTE risk. Oxford University Press 2022-10-18 /pmc/articles/PMC10234203/ /pubmed/36255271 http://dx.doi.org/10.1093/rheumatology/keac601 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Science Westerlind, Helga Kastbom, Alf Rönnelid, Johan Hansson, Monika Alfredsson, Lars Mathsson-Alm, Linda Serre, Guy Cornillet, Martin Holmdahl, Rikard Skriner, Karl Bang, Holger Klareskog, Lars Saevarsdottir, Saedis Lundberg, Karin Grönwall, Caroline Askling, Johan The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title | The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title_full | The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title_fullStr | The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title_full_unstemmed | The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title_short | The association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
title_sort | association between autoantibodies and risk for venous thromboembolic events among patients with rheumatoid arthritis |
topic | Clinical Science |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10234203/ https://www.ncbi.nlm.nih.gov/pubmed/36255271 http://dx.doi.org/10.1093/rheumatology/keac601 |
work_keys_str_mv | AT westerlindhelga theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT kastbomalf theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT ronnelidjohan theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT hanssonmonika theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT alfredssonlars theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT mathssonalmlinda theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT serreguy theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT cornilletmartin theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT holmdahlrikard theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT skrinerkarl theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT bangholger theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT klareskoglars theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT saevarsdottirsaedis theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT lundbergkarin theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT gronwallcaroline theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT asklingjohan theassociationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT westerlindhelga associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT kastbomalf associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT ronnelidjohan associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT hanssonmonika associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT alfredssonlars associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT mathssonalmlinda associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT serreguy associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT cornilletmartin associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT holmdahlrikard associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT skrinerkarl associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT bangholger associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT klareskoglars associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT saevarsdottirsaedis associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT lundbergkarin associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT gronwallcaroline associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis AT asklingjohan associationbetweenautoantibodiesandriskforvenousthromboemboliceventsamongpatientswithrheumatoidarthritis |