Periodontal sources of citrullinated antigens and TLR agonists related to RA
Anti-citrullinated protein autoantibodies (ACPA) precede the onset of clinical and subclinical rheumatoid arthritis (RA). ACPA are frequently generated in further chronic inflammatory diseases, e.g. chronic obstructive pulmonary disease, lupus, periodontitis (PD), characterized by citrullination and...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-08-01
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| Series: | Autoimmunity |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/08916934.2018.1527907 |
| _version_ | 1797684753221025792 |
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| author | Ljubomir Vitkov Matthias Hannig Bernd Minnich Martin Herrmann |
| author_facet | Ljubomir Vitkov Matthias Hannig Bernd Minnich Martin Herrmann |
| author_sort | Ljubomir Vitkov |
| collection | DOAJ |
| description | Anti-citrullinated protein autoantibodies (ACPA) precede the onset of clinical and subclinical rheumatoid arthritis (RA). ACPA are frequently generated in further chronic inflammatory diseases, e.g. chronic obstructive pulmonary disease, lupus, periodontitis (PD), characterized by citrullination and mucosal as well as systemic autoimmunity against citrullinated proteins. PD is of particular interest, as it exhibits two sources of citrullination, namely peptidylarginine deiminase 4 (PAD4) of periodontal neutrophils and neutrophil extracellular traps (NETs) as well as the PAD of Porphyromonas gingivalis (PPAD). Whereas the PAD4-citrullinated host peptides and/or proteins occur physiologically, PPAD-citrullinated ones appear under pathological conditions as neo-antigens. Frequently, the oral pathogens P. gingivalis and A. actinomycetemcomitans directly and indirectly participate in synovitis in RA, providing topical citrullination: P. gingivalis via PPAD and A. actinomycetemcomitans via leukotoxin A-mediated ROS-independent NET formation. In addition, transient bacteraemia due to tooth brushing indicates the possibility that citrullinated peptides and/or proteins from periodontium regularly enter the blood circulation. In this way, the mucosal firewall is evaded and the systemic immune response against citrullinated peptides and/or proteins is facilitated. However, the role of swallowed PD-derived sludge for the induction of oral tolerance remains to be established. We hypothesize (I) PD-driven endotoxemia may increase the host responsiveness to autoantigens via TLR4 activation and (II) this participates in development and propagation of RA (III) circulating PD-derived bacterial DNA is taken up by phagocytes, activates TLR9, and thus increases the responsiveness to autoantigens. |
| first_indexed | 2024-03-12T00:34:20Z |
| format | Article |
| id | doaj.art-a25b7f27244a47fc9558482a31cc0b50 |
| institution | Directory Open Access Journal |
| issn | 0891-6934 1607-842X |
| language | English |
| last_indexed | 2024-03-12T00:34:20Z |
| publishDate | 2018-08-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autoimmunity |
| spelling | doaj.art-a25b7f27244a47fc9558482a31cc0b502023-09-15T10:01:08ZengTaylor & Francis GroupAutoimmunity0891-69341607-842X2018-08-0151630430910.1080/08916934.2018.15279071527907Periodontal sources of citrullinated antigens and TLR agonists related to RALjubomir Vitkov0Matthias Hannig1Bernd Minnich2Martin Herrmann3University of SalzburgSaarland UniversityUniversity of SalzburgFriedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum ErlangenAnti-citrullinated protein autoantibodies (ACPA) precede the onset of clinical and subclinical rheumatoid arthritis (RA). ACPA are frequently generated in further chronic inflammatory diseases, e.g. chronic obstructive pulmonary disease, lupus, periodontitis (PD), characterized by citrullination and mucosal as well as systemic autoimmunity against citrullinated proteins. PD is of particular interest, as it exhibits two sources of citrullination, namely peptidylarginine deiminase 4 (PAD4) of periodontal neutrophils and neutrophil extracellular traps (NETs) as well as the PAD of Porphyromonas gingivalis (PPAD). Whereas the PAD4-citrullinated host peptides and/or proteins occur physiologically, PPAD-citrullinated ones appear under pathological conditions as neo-antigens. Frequently, the oral pathogens P. gingivalis and A. actinomycetemcomitans directly and indirectly participate in synovitis in RA, providing topical citrullination: P. gingivalis via PPAD and A. actinomycetemcomitans via leukotoxin A-mediated ROS-independent NET formation. In addition, transient bacteraemia due to tooth brushing indicates the possibility that citrullinated peptides and/or proteins from periodontium regularly enter the blood circulation. In this way, the mucosal firewall is evaded and the systemic immune response against citrullinated peptides and/or proteins is facilitated. However, the role of swallowed PD-derived sludge for the induction of oral tolerance remains to be established. We hypothesize (I) PD-driven endotoxemia may increase the host responsiveness to autoantigens via TLR4 activation and (II) this participates in development and propagation of RA (III) circulating PD-derived bacterial DNA is taken up by phagocytes, activates TLR9, and thus increases the responsiveness to autoantigens.http://dx.doi.org/10.1080/08916934.2018.1527907porphyromonas gingivalispadppadmucosal firewallcross-reactivitygcflps |
| spellingShingle | Ljubomir Vitkov Matthias Hannig Bernd Minnich Martin Herrmann Periodontal sources of citrullinated antigens and TLR agonists related to RA Autoimmunity porphyromonas gingivalis pad ppad mucosal firewall cross-reactivity gcf lps |
| title | Periodontal sources of citrullinated antigens and TLR agonists related to RA |
| title_full | Periodontal sources of citrullinated antigens and TLR agonists related to RA |
| title_fullStr | Periodontal sources of citrullinated antigens and TLR agonists related to RA |
| title_full_unstemmed | Periodontal sources of citrullinated antigens and TLR agonists related to RA |
| title_short | Periodontal sources of citrullinated antigens and TLR agonists related to RA |
| title_sort | periodontal sources of citrullinated antigens and tlr agonists related to ra |
| topic | porphyromonas gingivalis pad ppad mucosal firewall cross-reactivity gcf lps |
| url | http://dx.doi.org/10.1080/08916934.2018.1527907 |
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