Periodontal sources of citrullinated antigens and TLR agonists related to RA

Vitkov L, Hannig M, Minnich B, Herrmann M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Autoimmunity Informa Healthcare

Book Volume: 51

Pages Range: 304-309

Journal Issue: 6

DOI: 10.1080/08916934.2018.1527907

Abstract

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.

Authors with CRIS profile

Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Universität Salzburg (Paris Lodron Universität Salzburg) AT Austria (AT) Universität des Saarlandes (UdS) DE Germany (DE)

How to cite

APA:

Vitkov, L., Hannig, M., Minnich, B., & Herrmann, M. (2018). Periodontal sources of citrullinated antigens and TLR agonists related to RA. Autoimmunity, 51(6), 304-309. https://doi.org/10.1080/08916934.2018.1527907

MLA:

Vitkov, Ljubomir, et al. "Periodontal sources of citrullinated antigens and TLR agonists related to RA." Autoimmunity 51.6 (2018): 304-309.

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