Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis
Copyright © 2023 Martinsson, Di Matteo, Öhman, Johansson, Svärd, Mankia, Emery and Kastbom..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Frontiers in medicine - 10(2023) vom: 15., Seite 1176165 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Martinsson, Klara [VerfasserIn] |
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| Links: |
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| Themen: |
ACPA |
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| Anmerkungen: |
Date Revised 23.08.2023 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3389/fmed.2023.1176165 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM361004729 |
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| 245 | 1 | 0 | |a Antibodies to leukotoxin A from the periodontal pathogen Aggregatibacter actinomycetemcomitans in patients at an increased risk of rheumatoid arthritis |
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| 500 | |a Date Revised 23.08.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Copyright © 2023 Martinsson, Di Matteo, Öhman, Johansson, Svärd, Mankia, Emery and Kastbom. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ACPA | |
| 650 | 4 | |a Aggregatibacter actinomycetemcomitans | |
| 650 | 4 | |a periodontitis | |
| 650 | 4 | |a progression | |
| 650 | 4 | |a rheumatoid arthritis | |
| 700 | 1 | |a Di Matteo, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Öhman, Carina |e verfasserin |4 aut | |
| 700 | 1 | |a Johansson, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Svärd, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Mankia, Kulveer |e verfasserin |4 aut | |
| 700 | 1 | |a Emery, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Kastbom, Alf |e verfasserin |4 aut | |
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