Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis

Introduction Rheumatoid arthritis (RA) is an autoimmune disease marked by the production of autoantibodies (AAb) against citrullinated proteins/peptides (ACPA). The shared epitope (SE) in the HLA-DRB1 gene is a major genetic risk factor for RA and has been linked to ACPA production, particularly in...

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Autores: Graell, E, Delgado, JF, Gomez, AD, García-Marique, M, Rusiñol, M, Rodrigo, A, Berenguer-Llergo, A, Gratacos, J, Calvet, J
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Institut d'Investigació i Innovació Parc Taulí (I3PT)
Repositorio:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
OAI Identifier:oai:dnet:r-i3pt______::32596818e532d8a06799f870fd775301
Acceso en línea:https://i3pt.portalinvestigacion.com/publicaciones/7151
Access Level:acceso abierto
Palabra clave:anti-citrullinated peptide antibodies
autoantibodies
inflammatory arthritis
rheumatoid arthritis
shared epitope
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spelling Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritisGraell, EDelgado, JFGomez, ADGarcía-Marique, MRusiñol, MRodrigo, ABerenguer-Llergo, AGratacos, JCalvet, Janti-citrullinated peptide antibodiesautoantibodiesinflammatory arthritisrheumatoid arthritisshared epitopeIntroduction Rheumatoid arthritis (RA) is an autoimmune disease marked by the production of autoantibodies (AAb) against citrullinated proteins/peptides (ACPA). The shared epitope (SE) in the HLA-DRB1 gene is a major genetic risk factor for RA and has been linked to ACPA production, particularly in individuals exposed to environmental triggers such as smoking. However, the role of the SE itself, especially in its citrullinated form, as a target of humoral immunity in RA remains underexplored.Methods We analyzed autoantibodies against SE-containing peptides (SE-AAb) in 150 RA patients, 62 patients with psoriatic arthritis (PsA), and 204 healthy controls. HLA-DRB1 polymorphisms associated with the SE (QKRAA, QRRAA, RRRAA) were evaluated by PCR-SSO. IgG reactivity against native, citrullinated, and carbamylated SE peptides, in linear and cyclic conformations, was assessed using a custom ELISA.Results SE-AAb were detected in RA patients with frequencies ranging from 26.0% to 45.3%, depending on peptide conformation and post-translational modification, with the highest positivity observed against citrullinated SE peptides. Antibodies against cyclated citrullinated SE peptides were present in 45.3% of RA patients, compared with 21.6% of healthy controls. PsA patients also showed SE-AAb positivity, with frequencies ranging from 17.7% to 35.5%, displaying a pattern largely similar to RA. No significant association was observed between SE-AAb positivity and SE genetic carriage, and SE-AAb presence was not associated with clinical features of RA.Conclusion SE-AAb are present in RA patients, particularly against citrullinated SE peptides, but are not specific to RA, as similar reactivity is observed in PsA. The presence of these autoantibodies is independent of SE genetic carriage, suggesting that inflammatory conditions rather than genetic SE status may contribute to their generation. Further studies are needed to clarify the clinical relevance of SE-AAb in RA pathogenesis.FRONTIERS MEDIA SA2026info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://i3pt.portalinvestigacion.com/publicaciones/7151Frontiers in ImmunologyISSN: 16643224reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulíinstname:Institut d'Investigació i Innovació Parc Taulí (I3PT)Inglésinfo:eu-repo/semantics/openAccessoai:dnet:r-i3pt______::32596818e532d8a06799f870fd7753012026-06-21T15:30:37Z
dc.title.none.fl_str_mv Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
title Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
spellingShingle Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
Graell, E
anti-citrullinated peptide antibodies
autoantibodies
inflammatory arthritis
rheumatoid arthritis
shared epitope
title_short Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
title_full Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
title_fullStr Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
title_full_unstemmed Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
title_sort Presence of autoantibodies targeting the shared epitope in rheumatoid arthritis and psoriatic arthritis
dc.creator.none.fl_str_mv Graell, E
Delgado, JF
Gomez, AD
García-Marique, M
Rusiñol, M
Rodrigo, A
Berenguer-Llergo, A
Gratacos, J
Calvet, J
author Graell, E
author_facet Graell, E
Delgado, JF
Gomez, AD
García-Marique, M
Rusiñol, M
Rodrigo, A
Berenguer-Llergo, A
Gratacos, J
Calvet, J
author_role author
author2 Delgado, JF
Gomez, AD
García-Marique, M
Rusiñol, M
Rodrigo, A
Berenguer-Llergo, A
Gratacos, J
Calvet, J
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv anti-citrullinated peptide antibodies
autoantibodies
inflammatory arthritis
rheumatoid arthritis
shared epitope
topic anti-citrullinated peptide antibodies
autoantibodies
inflammatory arthritis
rheumatoid arthritis
shared epitope
description Introduction Rheumatoid arthritis (RA) is an autoimmune disease marked by the production of autoantibodies (AAb) against citrullinated proteins/peptides (ACPA). The shared epitope (SE) in the HLA-DRB1 gene is a major genetic risk factor for RA and has been linked to ACPA production, particularly in individuals exposed to environmental triggers such as smoking. However, the role of the SE itself, especially in its citrullinated form, as a target of humoral immunity in RA remains underexplored.Methods We analyzed autoantibodies against SE-containing peptides (SE-AAb) in 150 RA patients, 62 patients with psoriatic arthritis (PsA), and 204 healthy controls. HLA-DRB1 polymorphisms associated with the SE (QKRAA, QRRAA, RRRAA) were evaluated by PCR-SSO. IgG reactivity against native, citrullinated, and carbamylated SE peptides, in linear and cyclic conformations, was assessed using a custom ELISA.Results SE-AAb were detected in RA patients with frequencies ranging from 26.0% to 45.3%, depending on peptide conformation and post-translational modification, with the highest positivity observed against citrullinated SE peptides. Antibodies against cyclated citrullinated SE peptides were present in 45.3% of RA patients, compared with 21.6% of healthy controls. PsA patients also showed SE-AAb positivity, with frequencies ranging from 17.7% to 35.5%, displaying a pattern largely similar to RA. No significant association was observed between SE-AAb positivity and SE genetic carriage, and SE-AAb presence was not associated with clinical features of RA.Conclusion SE-AAb are present in RA patients, particularly against citrullinated SE peptides, but are not specific to RA, as similar reactivity is observed in PsA. The presence of these autoantibodies is independent of SE genetic carriage, suggesting that inflammatory conditions rather than genetic SE status may contribute to their generation. Further studies are needed to clarify the clinical relevance of SE-AAb in RA pathogenesis.
publishDate 2026
dc.date.none.fl_str_mv 2026
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://i3pt.portalinvestigacion.com/publicaciones/7151
url https://i3pt.portalinvestigacion.com/publicaciones/7151
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv FRONTIERS MEDIA SA
publisher.none.fl_str_mv FRONTIERS MEDIA SA
dc.source.none.fl_str_mv Frontiers in Immunology
ISSN: 16643224
reponame:r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
instname:Institut d'Investigació i Innovació Parc Taulí (I3PT)
instname_str Institut d'Investigació i Innovació Parc Taulí (I3PT)
reponame_str r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
collection r-I3PT. Repositorio Institucional Producción Científica del Institut d'Investigació i Innovació Parc Taulí
repository.name.fl_str_mv
repository.mail.fl_str_mv
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