HYPOTHESIS - Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated RA

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Med Hypotheses. 2009 Jun;72(6):732-5. Epub 2009 Feb 25.

Porphyromonas gingivalis may play an important role in the

pathogenesis of periodontitis-associated rheumatoid arthritis.

Liao F, Li Z, Wang Y, Shi B, Gong Z, Cheng X.

Key Laboratory for Oral Biomedical Engineering of Ministry of

Education, School and Hospital of Stomatology, Wuhan University, 237#

Luo Yu Road, Wuhan, Hubei, PR China.

Rheumatoid arthritis (RA) is a common, systemic autoimmune disease

which leads to destruction of the joint architecture and consequent

disability. Although the aetiology of RA remains unknown, accumulating

studies have established a strong association between RA and

periodontitis (PD). Recently, anti-cyclic citrullinated peptide

(anti-CCP) autoantibody and citrullinated peptide have been realized

to be involved in the breaking of self-tolerance and development of

autoimmune in RA. The citrullinated peptide is generated by

post-translational modification (citrullination) of protein-bound

arginine by peptidylarginine deiminase (PAD). Porphyromonas

gingivalis(P. gingivalis), the major aetiological agent of PD and the

only bacterium known to express a PAD enzyme, has been reported to be

significantly associated with RA. The antibody titers to P. gingivalis

are significantly increased in patients with RA and P. gingivalis

antibody titers are significantly correlated with anti-CCP antibody

isotypes that are specific to RA. Recent study indicates that the

major synovial targets of the RA-specific anti-CCP autoantibodies are

deiminated forms of the alpha- and beta- chains of fibrin. Meanwhile,

it is also confirmed that bacterial PAD produced by P. gingivalis has

the capacity of deiminating arginine in fibrin found in the

periodontal lesion. What's more, it has been demonstrated that

citrullination of HLA binding peptide causes a 100-fold increase in

peptide-MHC affinity and leads to the activation CD4(+)T cells in HLA

DRB1 0401 transgenic mice. Therefore, we postulate that P. gingivalis

may play a crucial role in the pathogenesis of

periodontitis-associated RA. P. gingivalis, which colonizes in the

oral cavity, produces PAD enzyme continuously that leads to the

citrullination of RA autoantigen such as fibrin in synovium joint.

These PAD engendered antigens, presented in association with major

histocompatibility complex (MHC) molecules by antigen-presenting cells

(APC), ultimately lead to production of the anti-CCP antibody. The

anti-CCP antibodies form immune complexes with citrullinated proteins,

which can be bound by inflammatory cells via their Fc receptors. The

roles of these immune complexes and inflammatory cells are mediated by

a complex cascade involving complement activation. These mechanisms

result in a release of mediators of inflammation and joint destruction

ultimately leading to the onset of RA.

This hypothesis reveals that oral bacterial infection may play a role

in peptide citrullination which might be involved in loss of

self-tolerance and development of autoimmune in RA.

PMID: 19246161

http://www.ncbi.nlm.nih.gov/pubmed/19246161

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