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Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis
OBJECTIVES: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the p...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435988/ https://www.ncbi.nlm.nih.gov/pubmed/37601773 http://dx.doi.org/10.3389/fmed.2023.1176165 |
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author | Martinsson, Klara Di Matteo, Andrea Öhman, Carina Johansson, Anders Svärd, Anna Mankia, Kulveer Emery, Paul Kastbom, Alf |
author_facet | Martinsson, Klara Di Matteo, Andrea Öhman, Carina Johansson, Anders Svärd, Anna Mankia, Kulveer Emery, Paul Kastbom, Alf |
author_sort | Martinsson, Klara |
collection | PubMed |
description | OBJECTIVES: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. METHODS: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. RESULTS: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). CONCLUSION: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research. |
format | Online Article Text |
id | pubmed-10435988 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104359882023-08-19 Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis Martinsson, Klara Di Matteo, Andrea Öhman, Carina Johansson, Anders Svärd, Anna Mankia, Kulveer Emery, Paul Kastbom, Alf Front Med (Lausanne) Medicine OBJECTIVES: Periodontitis and underlying bacteria have been linked to the development of rheumatoid arthritis (RA). One suggested pathogen is Aggregatibacter actinomycetemcomitans (A.a.), which expresses leukotoxin A (LtxA) that can citrullinate human proteins, providing a possible trigger for the production of anti-citrullinated protein antibodies (ACPA). In this study, we seek to determine the presence of antibodies toward LtxA in patients at risk of developing RA. METHODS: Two prospective observational patient cohorts (one Swedish and one British) with symptomatic at-risk patients were studied. Anti-LtxA antibodies were analyzed by a cell-based neutralization assay in baseline serum and compared to 100 Swedish blood donors that served as controls. RESULTS: Serum anti-LtxA levels or positivity did not differ between patients and blood donors. In the British cohort, anti-LtxA was more prevalent among ACPA-positive arthralgia patients compared with ACPA-negative arthralgia cases (24% vs. 13%, p < 0.0001). In the Swedish at-risk cohort, anti-LtxA positive patients were at increased risk of progression to arthritis (hazard ratio (HR) 2.10, 95% CI 1.04–4.20), but this was not confirmed in the UK at-risk cohort (HR 0.99, CI 0.60–1.65). CONCLUSION: Serum anti-LtxA is not elevated before RA diagnosis, and associations with disease progression and ACPA levels differ between populations. Other features of the oral microbiome should be explored in upcoming periodontitis-related RA research. Frontiers Media S.A. 2023-08-03 /pmc/articles/PMC10435988/ /pubmed/37601773 http://dx.doi.org/10.3389/fmed.2023.1176165 Text en Copyright © 2023 Martinsson, Di Matteo, Öhman, Johansson, Svärd, Mankia, Emery and Kastbom. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Martinsson, Klara Di Matteo, Andrea Öhman, Carina Johansson, Anders Svärd, Anna Mankia, Kulveer Emery, Paul Kastbom, Alf Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title | Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title_full | Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title_fullStr | Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title_full_unstemmed | Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title_short | Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
title_sort | antibodies to leukotoxin a from the periodontal pathogen aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10435988/ https://www.ncbi.nlm.nih.gov/pubmed/37601773 http://dx.doi.org/10.3389/fmed.2023.1176165 |
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