Is Citrullination the Missing Link between Periodontal Disease and Rheumatoid Arthritis?

详细信息    查看全文

• 作者：Anna B. Montgomery ; Elena B. Lugli ; Patrick J. Venables
• 关键词：Rheumatoid arthritis ; Periodontitis ; Citrullination ; Anti ; citrullinated protein antibodies (ACPA) ; Peptidylarginine deiminase (PAD) ; Etiology ; Porphyromonas gingivalis ; PPAD
• 刊名：Current Oral Health Reports
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：2
• 期：1
• 页码：30-36
• 全文大小：192KB
• 参考文献：Papers of particular interest, published recently, have been highlighted as: 鈥?Of importance 鈥⑩€?Of major importance1.Wegner N, Lundberg K, Kinloch A, et al. Autoimmunity to specific citrullinated proteins gives the first clues to the etiology of rheumatoid arthritis. Immunol Rev. 2010;233(1):34鈥?4.PubMed CrossRef
  2.Wang S, Wang Y. Peptidylarginine deiminases in citrullination, gene regulation, health and pathogenesis. Biochim Biophys Acta. 2013;1829(10):1126鈥?5.PubMed Central PubMed CrossRef
  3.Kinloch A, Lundberg K, Wait R, et al. Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis Rheum. 2008;58(8):2287鈥?5.PubMed CrossRef
  4.Nesse W, Westra J, van der Wal JE, et al. The periodontium of periodontitis patients contains citrullinated proteins which may play a role in ACPA (anti-citrullinated protein antibody) formation. J Clin Periodontol. 2012;39(7):599鈥?07.PubMed CrossRef
  5.Ishida-Yamamoto A, Senshu T, Takahashi H, et al. Decreased deiminated keratin K1 in psoriatic hyperproliferative epidermis. J Invest Dermatol. 2000;114(4):701鈥?.PubMed CrossRef
  6.Jang B, Ishigami A, Maruyama N, et al. Peptidylarginine deiminase and protein citrullination in prion diseases: strong evidence of neurodegeneration. Prion. 2013;7(1):42鈥?.PubMed Central PubMed CrossRef
  7.Moscarello MA, Lei H, Mastronardi FG, et al. Inhibition of peptidyl-arginine deiminases reverses protein-hypercitrullination and disease in mouse models of multiple sclerosis. Dis Model Mech. 2013;6(2):467鈥?8.PubMed Central PubMed CrossRef
  8.Scher JU, Ubeda C, Equinda M, et al. Periodontal disease and the oral microbiota in new-onset rheumatoid arthritis. Arthritis Rheum. 2012;64(10):3083鈥?4.PubMed Central PubMed CrossRef
  9.de Smit M, Westra J, Vissink A, et al. Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study. Arthritis Research & Therapy 2012:14:R222.
  10.Dissick A, Redman RS, Jones M, et al. Association of periodontitis with rheumatoid arthritis: a pilot study. J Periodontol. 2010;81(2):223鈥?0.PubMed CrossRef
  11.de Pablo P, Dietrich T, McAlindon TE. Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol. 2008;35(1):70鈥?.PubMed
  12.Kasser UR, Gleissner C, Dehne F, et al. Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum. 1997;40(12):2248鈥?1.PubMed CrossRef
  13.Abdelsalam SK, Hashim NT, Elsalamabi EM, et al. Periodontal status of rheumatoid arthritis patients in khartoum state. BMC Res Notes. 2011;4:460.PubMed Central PubMed CrossRef
  14.Pischon N, Pischon T, Kr枚ger J, et al. Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol. 2008;79(6):979鈥?6.PubMed CrossRef
  15.Tolo K, Jorkjend L. Serum antibodies and loss of periodontal bone in patients with rheumatoid arthritis. J Clin Periodontol. 1990;17(5):288鈥?1.PubMed CrossRef
  16.Susanto H, Nesse W, Kertia N, et al. Prevalence and severity of periodontitis in Indonesian patients with rheumatoid arthritis. J Periodontol. 2013;84(8):1067鈥?4.PubMed CrossRef
  17.Rosamma J, Rajappan S, Nath SG, et al. Association between chronic periodontitis and rheumatoid arthritis: a hospital-based case-control study. Rheumatol Int. 2013;33(1):103鈥?.CrossRef
  18.Rutger Persson, G., Rheumatoid arthritis and periodontitis - inflammatory and infectious connections. Review of the literature. J Oral Microbiol, 2012;4.
  19.鈥?/div>Mikuls TR, Payne JB, Yu F, et al. Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014;66(5):1090鈥?00. An up-to-date, well-controlled study documenting the links between perionditis, Porphyromonas gingivalis infection and seropositive rheumatoid arthritis. PubMed CrossRef
  20.Gonzalez, S.M., Payne JB, Yu F, et al., Alveolar bone loss is associated with circulating anti-citrullinated protein antibody (ACPA) in rheumatoid arthritis patients. J Periodontol, 2014: p. 1-16.
  21.Mercado FB, Marshall RI, Klestov AC, et al. Relationship between rheumatoid arthritis and periodontitis. J Periodontol. 2001;72(6):779鈥?7.PubMed CrossRef
  22.Holoshitz J. The rheumatoid arthritis HLA-DRB1 shared epitope. Curr Opin Rheumatol. 2010;22(3):293鈥?.PubMed Central PubMed CrossRef
  23.Hill JA, Southwood S, Sette A, et al. 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鈥?1.PubMed CrossRef
  24.Bonfil JJ, Dillier FL, Mercier P, et al. A "case control" study on the role of HLA DR4 in severe periodontitis and rapidly progressive periodontitis. Identification of types and subtypes using molecular biology (PCR.SSO). J Clin Periodontol. 1999;26(2):77鈥?4.PubMed CrossRef
  25.Menard L, Saadoun D, Isnardi I, et al. The PTPN22 allele encoding an R620W variant interferes with the removal of developing autoreactive B cells in humans. J Clin Invest. 2011;121(9):3635鈥?4.PubMed Central PubMed CrossRef
  26.Feitsma AL, Toes RE, Begovich AB, et al. Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858 T-allele in anti-citrullinated peptide antibody positive patients. Rheumatology (Oxford). 2007;46(7):1092鈥?.CrossRef
  27.Klareskog L, Malmstr枚m V, Lundberg K, et al. Smoking, citrullination and genetic variability in the immunopathogenesis of rheumatoid arthritis. Semin Immunol. 2011;23(2):92鈥?.PubMed CrossRef
  28.Makrygiannakis D, Hermansson M, Ulfgren AK, et al. Smoking increases peptidylarginine deiminase 2 enzyme expression in human lungs and increases citrullination in BAL cells. Ann Rheum Dis. 2008;67(10):1488鈥?2.
  29.Albandar JM, Streckfus CF, Adesanya MR, et al. Cigar, pipe, and cigarette smoking as risk factors for periodontal disease and tooth loss. J Periodontol. 2000;71(12):1874鈥?1.PubMed CrossRef
  30.Genco RJ, Borgnakke WS. Risk factors for periodontal disease. Periodontol 2000. 2013;62(1):59鈥?4.PubMed CrossRef
  31.Schellekens GA, de Jong BA, van den Hoogen FH, et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998;101(1):273鈥?1.PubMed Central PubMed CrossRef
  32.Aletaha D, Neogi T, Silman AJ, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69(9):1580鈥?.PubMed CrossRef
  33.Fisher BA, Plant D, Brode M, et al. Antibodies to citrullinated alpha-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis. Ann Rheum Dis. 2011;70(6):1095鈥?.PubMed CrossRef
  34.van der Woude D, Syversen SW, van der Voort EI, et al. The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis. Ann Rheum Dis. 2010;69(6):1110鈥?.PubMed CrossRef
  35.van de Stadt LA, van der Horst AR, de Koning MH, et al. The extent of the anti-citrullinated protein antibody repertoire is associated with arthritis development in patients with seropositive arthralgia. Ann Rheum Dis. 2011;70(1):128鈥?3.PubMed CrossRef
  36.Aubart F, Crestani B, Nicaise-Roland P, et al. High levels of anti-cyclic citrullinated peptide autoantibodies are associated with co-occurrence of pulmonary diseases with rheumatoid arthritis. J Rheumatol. 2011;38(6):979鈥?2.PubMed CrossRef
  37.Rantap盲盲-Dahlqvist S, de Jong BA, Berglin E, et al. Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum. 2003;48(10):2741鈥?.PubMed CrossRef
  38.van de Stadt LA, de Koning MH, van de Stadt RJ, et al. Development of the anti-citrullinated protein antibody repertoire prior to the onset of rheumatoid arthritis. Arthritis Rheum. 2011;63(11):3226鈥?3.PubMed CrossRef
  39.Sokolove J, Bromberg R, Deane KD, et al. Autoantibody epitope spreading in the pre-clinical phase predicts progression to rheumatoid arthritis. PLoS One. 2012;7(5):e35296.PubMed Central PubMed CrossRef
  40.Kleyer A, Finzel S, Rech J, et al. Bone loss before the clinical onset of rheumatoid arthritis in subjects with anticitrullinated protein antibodies. Ann Rheum Dis. 2014;73(5):854鈥?0.PubMed CrossRef
  41.Harre U, Georgess D, Bang H, et al. Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 2012;122(5):1791鈥?02.PubMed Central PubMed CrossRef
  42.鈥?/div>Sokolove J, Zhao X, Chandra PE, et al. Immune complexes containing citrullinated fibrinogen costimulate macrophages via Toll-like receptor 4 and Fcgamma receptor. Arthritis Rheum. 2011;63(1):53鈥?2. This study decribes two major pathogenic mechanisms whereby immune complexes containg autantibodies and their citrullinated antigens mediate inflammation and tissue destruction in the rheumatoid joint. PubMed Central PubMed CrossRef
  43.Koziel J, Bryzek D, Sroka A, et al. Citrullination alters immunomodulatory function of LL-37 essential for prevention of endotoxin-induced sepsis. J Immunol. 2014;192(11):5363鈥?2.PubMed CrossRef
  44.Bielecka E, Scavenius C, Kantyka T, et al. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity. J Biol Chem. 2014;289(47):32481鈥?.PubMed CrossRef
  45.Wegner N, Wait R, Sroka A, et al. Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and 伪-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum. 2010;62(9):2662鈥?2.PubMed Central PubMed CrossRef
  46.Ireland JM, Unanue ER. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells. J Exp Med. 2011;208(13):2625鈥?2.PubMed Central PubMed CrossRef
  47.Ireland J, Herzog J, Unanue ER. Cutting edge: unique T cells that recognize citrullinated peptides are a feature of protein immunization. J Immunol. 2006;177(3):1421鈥?.PubMed CrossRef
  48.Lappin DF, Apatzidou D, Quirke AM, et al. Influence of periodontal disease, Porphyromonas gingivalis and cigarette smoking on systemic anti-citrullinated peptide antibody titres. J Clin Periodontol. 2013 Oct;40(10):907鈥?5.
  49.鈥⑩€?/div>de Pablo P, Dietrich T, Chapple IL, et al. The autoantibody repertoire in periodontitis: a role in the induction of autoimmunity to citrullinated proteins in rheumatoid arthritis? Ann Rheum Dis. 2014 Mar;73(3):580鈥?. This study was the first to show low levels of autoreactivity to non-citrullinated variants of rheumatoid autoantigens in patients with periodontitis.
  50.Quirke AM, Lugli EB, Wegner N, et al. Heightened immune response to autocitrullinated Porphyromonas gingivalis peptidylarginine deiminase: a potential mechanism for breaching immunologic tolerance in rheumatoid arthritis. Ann Rheum Dis. 2014 Jan;73(1):263鈥?.
  51.Kharlamova, N., Sherina N, Quirke AM, et al. Antibodies to Porphyromonas gingivalis as an etiological clue to the development of anti-citrullinated protein antibody positive rheumatoid arthritis [abstract]. Arthritis Rheum 2013;65(Suppl 10). doi:10.鈥?002/鈥媋rt.鈥?013.鈥?5.鈥媔ssue-s10 .
  52.Suzuki A, Yamada R, Chang X, et al. Functional haplotypes of PADI4, encoding citrullinating enzyme peptidylarginine deiminase 4, are associated with rheumatoid arthritis. Nat Genet. 2003;34(4):395鈥?02.PubMed CrossRef
  53.Harvey GP, Fitzsimmons TR, Dhamarpatni AA, et al. Expression of peptidylarginine deiminase-2 and -4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva. J Periodontal Res. 2013;48(2):252鈥?1.PubMed CrossRef
  54.Vitkov L, Klappacher M, Hannig M, et al. Neutrophil fate in gingival crevicular fluid. Ultrastruct Pathol. 2010;34(1):25鈥?0.PubMed CrossRef
  55.Dwivedi N, Radic M. Citrullination of autoantigens implicates NETosis in the induction of autoimmunity. Ann Rheum Dis. 2014;73(3):483鈥?1.PubMed CrossRef
  56.Sur Chowdhury C, Giaglis S, Walker UA, et al. Enhanced neutrophil extracellular trap generation in rheumatoid arthritis: analysis of underlying signal transduction pathways and potential diagnostic utility. Arthritis Res Ther. 2014;16(3):R122.PubMed Central PubMed CrossRef
  57.Pratesi F, Dioni I, Tommasi C, et al. Antibodies from patients with rheumatoid arthritis target citrullinated histone 4 contained in neutrophils extracellular traps. Ann Rheum Dis. 2014;73(7):1414鈥?2.PubMed CrossRef
  58.Lundberg K, Kinloch A, Fisher BA, et al. Antibodies to citrullinated alpha-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 2008;58(10):3009鈥?9.PubMed CrossRef
  59.Kinloch AJ, Alzabin S, Brintnell W, et al. Immunization with Porphyromonas gingivalis enolase induces autoimmunity to mammalian 伪-enolase and arthritis in DR4-IE-transgenic mice. Arthritis Rheum. 2011;63(12):3818鈥?3.PubMed CrossRef
  60.Quirke, A.-M., Perry E, Cartwright A, et al. Bronchiectasis: a model for chronic bacterial infection inducing autoimmunity in rheumatoid arthritis [abstract no. 433]. 2014 ACR/ARHP Annual Meeting; 14鈥?9 Nov 2014; Boston.
  61.Chen HH, Huang N, Chen YM, et al. Association between a history of periodontitis and the risk of rheumatoid arthritis: a nationwide, population-based, case-control study. Ann Rheum Dis. 2013;72(7):1206鈥?1.PubMed CrossRef
  
• 作者单位：Anna B. Montgomery (1)
  Elena B. Lugli (1)
  Patrick J. Venables (1)
  
  1. Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7FY, UK
  
• 刊物类别：Oral and Maxillofacial Surgery;
• 刊物主题：Oral and Maxillofacial Surgery;
• 出版者：Springer International Publishing
• ISSN：2196-3002

文摘

Connections between periodontitis (PD) and rheumatoid arthritis (RA) are suggested by an increased prevalence of PD in RA, shared environmental and genetic risk factors, and correlating levels of severity when the two diseases occur together. Here, we compare and contrast the results from numerous studies documenting this association, and highlight the involvement of citrullination in the development of autoimmunity leading to the destructive pathology that characterizes RA. The contribution of citrullination to RA may occur in at least three distinct phases: (i) the initial breakdown of tolerance leading to autoimmunity; (ii) the maturation of the citrulline specificity of the autoantibody response; and (iii) the pro-inflammatory effect of citrullinated proteins themselves in established disease. We conclude that citrullination is more than a 鈥榤issing link鈥? rather, it is an active process in the evolution of low levels of autoimmunity found in PD into the pathogenic anti-citrullinated protein response specific to RA. Keywords Rheumatoid arthritis Periodontitis Citrullination Anti-citrullinated protein antibodies (ACPA) Peptidylarginine deiminase (PAD) Etiology Porphyromonas gingivalis PPAD