Porphyromonas Gingivalis and the Pathogenesis of Rheumatoid Arthritis: Analysis of Various Compartments Including the Synovial Tissue

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2013 Jun 20

PMID 23777892

Citations 38

Authors

Michele Ciro Totaro

Paola Cattani

Francesco Ria

Barbara Tolusso

Elisa Gremese

Anna Laura Fedele

Sara DOnghia

Simona Marchetti

Gabriele Di Sante

Silvia Canestri

Gianfranco Ferraccioli

Affiliations

Soon will be listed here.

Abstract

Introduction: We evaluated the presence of Porphyromonas gingivalis (Pg) DNA in the synovial tissue through synovial biopsy and in other compartments of rheumatoid arthritis (RA) patients in comparison with patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed.

Methods: Peripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and synovial tissue samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 had undifferentiated peripheral inflammatory arthritis - UPIA). Demographic, clinical, laboratory and immunological data were recorded. The presence of Pg DNA was evaluated through PCR. The HLA-DR haplotype was assessed for 45 patients with RA and UPIA.

Results: No differences arose in the positivity for Pg DNA in the sub-gingival plaque, PB and SF samples between RA and the cohort of other arthritides. Full PB samples showed a higher positivity for Pg DNA than plasma samples (11.8% vs. 1.5%, P = 0.04). Patients with RA showed a higher positivity for Pg DNA in the synovial tissue compared to controls (33.3% vs. 5.9%, P <0.01). UPIA and RA patients carrying the HLA DRB1*04 allele showed a higher positivity for Pg DNA in the synovial tissue compared to patients negative for the allele (57.1% vs. 16.7%, P = 0.04). RA patients positive for Pg DNA in the sub-gingival plaque had a lower disease duration and a higher peripheral blood leucocyte and neutrophil count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies.

Conclusions: The presence of Pg DNA in the synovial tissue of RA patients suggests a pathogenic role of the bacterium. The higher positivity of Pg DNA in full peripheral blood and synovial tissue samples compared to plasma and synovial fluid suggests a possible intracellular localization of Pg, in particular in patients positive for HLA-DR4.

Citing Articles

The PerioGene North study reveals that periodontal inflammation and advanced jawbone loss in periodontitis associate with serum gingipain antibodies but not with systemic autoimmunity.

Kindstedt E, de Vries C, Wanman M, Potempa B, Potempa J, Lindquist S Front Immunol. 2025; 15:1504975.

PMID: 39877342 PMC: 11772355. DOI: 10.3389/fimmu.2024.1504975.

Molecular Mimicry Between Gut Microbiome and Rheumatoid Arthritis: Current Concepts.

Muruganandam A, Migliorini F, Jeyaraman N, Vaishya R, Balaji S, Ramasubramanian S Med Sci (Basel). 2024; 12(4).

PMID: 39728421 PMC: 11677576. DOI: 10.3390/medsci12040072.

Secrets and lies of host-microbial interactions: MHC restriction and trans-regulation of T cell trafficking conceal the role of microbial agents on the edge between health and multifactorial/complex diseases.

Ria F, Delogu G, Ingrosso L, Sali M, Di Sante G Cell Mol Life Sci. 2024; 81(1):40.

PMID: 38216734 PMC: 11071949. DOI: 10.1007/s00018-023-05040-y.

Periodontitis and periodontopathic bacteria as risk factors for rheumatoid arthritis: A review of the last 10 years.

Kobayashi T, Bartold P Jpn Dent Sci Rev. 2023; 59:263-272.

PMID: 37674898 PMC: 10477376. DOI: 10.1016/j.jdsr.2023.08.002.

Host insulin resistance caused by -review of recent progresses.

Jia S, Li X, Du Q Front Cell Infect Microbiol. 2023; 13:1209381.

PMID: 37520442 PMC: 10373507. DOI: 10.3389/fcimb.2023.1209381.

References

Scher J, Ubeda C, Equinda M, Khanin R, Buischi Y, Viale A . Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012; 64(10):3083-94. PMC: 3428472. DOI: 10.1002/art.34539. View

MacGregor A, Snieder H, Rigby A, Koskenvuo M, Kaprio J, Aho K . Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum. 2000; 43(1):30-7. DOI: 10.1002/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B. View

Hitchon C, El-Gabalawy H . Infection and rheumatoid arthritis: still an open question. Curr Opin Rheumatol. 2011; 23(4):352-7. DOI: 10.1097/BOR.0b013e3283477b7b. View

Cantley M, Haynes D, Marino V, Bartold P . Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. J Clin Periodontol. 2011; 38(6):532-41. DOI: 10.1111/j.1600-051X.2011.01714.x. View

Nonnenmacher C, Dalpke A, Zimmermann S, Flores-de-Jacoby L, Mutters R, Heeg K . DNA from periodontopathogenic bacteria is immunostimulatory for mouse and human immune cells. Infect Immun. 2003; 71(2):850-6. PMC: 145359. DOI: 10.1128/IAI.71.2.850-856.2003. View

Moen K, Brun J, Valen M, Skartveit L, Eribe E, Olsen I . Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol. 2007; 24(6):656-63. View

Oldstone M . Molecular mimicry and autoimmune disease. Cell. 1987; 50(6):819-20. DOI: 10.1016/0092-8674(87)90507-1. View

Trombone A, Claudino M, Colavite P, de Assis G, Avila-Campos M, Silva J . Periodontitis and arthritis interaction in mice involves a shared hyper-inflammatory genotype and functional immunological interferences. Genes Immun. 2010; 11(6):479-89. DOI: 10.1038/gene.2010.13. View

Kinloch A, Alzabin S, Brintnell W, Wilson E, Barra L, Wegner N . Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian α-enolase and arthritis in DR4-IE-transgenic mice. Arthritis Rheum. 2011; 63(12):3818-23. DOI: 10.1002/art.30639. View

10.

Padyukov L, Silva C, Stolt P, Alfredsson L, Klareskog L . A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis. Arthritis Rheum. 2004; 50(10):3085-92. DOI: 10.1002/art.20553. View

11.

Mikuls T, Payne J, Reinhardt R, Thiele G, Maziarz E, Cannella A . Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol. 2008; 9(1):38-42. PMC: 2748386. DOI: 10.1016/j.intimp.2008.09.008. View

12.

Yanni G, Whelan A, Feighery C, Bresnihan B . Analysis of cell populations in rheumatoid arthritis synovial tissues. Semin Arthritis Rheum. 1992; 21(6):393-9. DOI: 10.1016/0049-0172(92)90040-k. View

13.

Fagundes J, Monoo L, Tubero Euzebio Alves V, Pannuti C, Cortelli S, Cortelli J . Porphyromonas gingivalis is associated with protease-activated receptor-2 upregulation in chronic periodontitis. J Periodontol. 2011; 82(11):1596-601. DOI: 10.1902/jop.2011.110073. View

14.

Loyola-Rodriguez J, Martinez-Martinez R, Abud-Mendoza C, Patino-Marin N, Seymour G . Rheumatoid arthritis and the role of oral bacteria. J Oral Microbiol. 2011; 2. PMC: 3084578. DOI: 10.3402/jom.v2i0.5784. View

15.

Belibasakis G, Bostanci N, Reddi D . Regulation of protease-activated receptor-2 expression in gingival fibroblasts and Jurkat T cells by Porphyromonas gingivalis. Cell Biol Int. 2009; 34(3):287-92. DOI: 10.1042/CBI20090290. View

16.

Hill J, Southwood S, Sette A, Jevnikar A, Bell D, Cairns E . Cutting edge: the conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. J Immunol. 2003; 171(2):538-41. DOI: 10.4049/jimmunol.171.2.538. View

17.

Rosenstein E, Greenwald R, Kushner L, Weissmann G . Hypothesis: the humoral immune response to oral bacteria provides a stimulus for the development of rheumatoid arthritis. Inflammation. 2005; 28(6):311-8. DOI: 10.1007/s10753-004-6641-z. View

18.

Slots J, Ashimoto A, Flynn M, Li G, Chen C . Detection of putative periodontal pathogens in subgingival specimens by 16S ribosomal DNA amplification with the polymerase chain reaction. Clin Infect Dis. 1995; 20 Suppl 2:S304-7. DOI: 10.1093/clinids/20.supplement_2.s304. View

19.

Mercado F, Marshall R, Bartold P . Inter-relationships between rheumatoid arthritis and periodontal disease. A review. J Clin Periodontol. 2003; 30(9):761-72. DOI: 10.1034/j.1600-051x.2003.00371.x. View

20.

de Smit M, Brouwer E, Vissink A, van Winkelhoff A . Rheumatoid arthritis and periodontitis; a possible link via citrullination. Anaerobe. 2011; 17(4):196-200. DOI: 10.1016/j.anaerobe.2011.03.019. View