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Immune dysregulation and pathogenic pathways mediated by common infections in rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is one of the world’s most prevalent inflammatory autoimmune diseases, affecting between 0.4 and 1.3% of the population. The susceptibility to RA appears to be influenced by a complex interaction between a favorable genetic background and the existence of a specific immune reaction against a wide range of environmental variables. Among the known environmental variables, infections are believed to have a significant role in promoting the formation of autoimmune disorders, which are frequently caused by specific microorganisms. Infections have been linked to RA in recent medical studies. In this study, we selected the most prevalent infections associated with RA from the literature and described the data confirming their pathogenic role in RA. Our investigation included Mycobacterium, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Proteus mirabilis, Epstein-Barr virus, parvovirus, and Prevotella copri.

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References

  • Adland E, Klenerman P, Goulder P, Matthews P (2015) Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era. Fron Microbiol 6:1016

    Google Scholar 

  • Aguas A, Esaguy N, Sunkel C, Silva M (1990) Cross-reactivity and sequence homology between the 65-kilodalton mycobacterial heat shock protein and human lactoferrin, transferrin, and DR beta subsets of major histocompatibility complex class II molecules. Infect Immun 58:1461–1470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ali S, Salloom DF (2020) A novel finding of IL-9 genetic polymorphism (rs17317275) and serum level in rheumatoid arthritis patients infected with CMV. Plant Arch 20:582–587

    Google Scholar 

  • Alivernini S, Tolusso B, Petricca L, Ferraccioli G, Gremese E (2019) Rheumatoid Arthritis. Mosaic Autoimmun 501–526 Elsevier

  • Alpizar-Rodriguez D, Lesker TR, Gronow A, Gilbert B, Raemy E, Lamacchia C, Gabay C, Finckh A, Strowig T (2019) Prevotella copri in individuals at risk for rheumatoid arthritis. Ann Rheum Dis 78:590–593

    Article  CAS  PubMed  Google Scholar 

  • Altschuler EL (1999) Parvovirus B19 and the pathogenesis of rheumatoid arthritis: a case for historical reasoning. The Lancet 354:1026–1027

    Article  CAS  Google Scholar 

  • Araújo VMA, Melo IM, Lima V (2015) Relationship between periodontitis and rheumatoid arthritis: review of the literature. Mediat inflamm 2015

  • Azadeh H, Alizadeh-Navaei R, Rezaiemanesh A, Rajabinejad M (2022) Immune-related adverse events (irAEs) in ankylosing spondylitis (AS) patients treated with interleukin (IL)-17 inhibitors: a systematic review and meta-analysis. Inflammopharmacol 30:435–451

    Article  CAS  Google Scholar 

  • Bartold PM, Marino V, Cantley M, Haynes DR (2010) Effect of Porphyromonas gingivalis-induced inflammation on the development of rheumatoid arthritis. J Clinperio Dontol 37:405–411

    Google Scholar 

  • Bassyouni RH, Dwedar RA, Ezzat EM, Marzaban RN, Nassr MH, Rashid L (2019) Elevated Cytomegalovirus and Epstein-Barr virus burden in rheumatoid arthritis: A true pathogenic role or just a coincidence. Egypt Rheumatol 41:255–259

    Article  Google Scholar 

  • Batool H, Afzal N, Shahzad F, Kashif M (2016) Relationship between rheumatoid arthritis and chronic periodontitis. J Med Radiol Pathol Surg 2:11–14

    Article  Google Scholar 

  • Birkenfeld P, Haratz N, Klein G, Sulitzeanu D (1990) Cross-reactivity between the EBNA-1 p107 peptide, collagen, and keratin: implications for the pathogenesis of rheumatoid arthritis. Clin Immunol Immunopathol 54:14–25

    Article  CAS  PubMed  Google Scholar 

  • Bizzaro N, Mazzanti G, Tonutti E, Villalta D, Tozzoli R (2001) Diagnostic accuracy of the anti-citrulline antibody assay for rheumatoid arthritis. Clin Chem 47:1089–1093

    Article  CAS  PubMed  Google Scholar 

  • Blaschke S, Schwarz G, Moneke D, Binder L, Müller G, Reuss-Borst M (2000) Epstein-Barr virus infection in peripheral blood mononuclear cells, synovial fluid cells, and synovial membranes of patients with rheumatoid arthritis. J Rheumatol 27:866–873

    CAS  PubMed  Google Scholar 

  • Bo M, Erre GL, Niegowska M, Piras M, Taras L, Longu MG, Passiu G, Sechi LA (2018) Interferon regulatory factor 5 is a potential target of autoimmune response triggered by Epstein-Barr virus and Mycobacterium avium subsp. paratuberculosis in rheumatoid arthritis: investigating a mechanism of molecular mimicry. Clin Exp Rheumatol 36:376–381

    PubMed  Google Scholar 

  • Bo M, Jasemi S, Uras G, Erre GL, Passiu G, Sechi LA (2020) Role of infections in the pathogenesis of rheumatoid arthritis: focus on mycobacteria. Microorganisms 8:1459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Breedveld F, Van Embden JA, Schaar C, Van Eden W, Cohen I, De Vries RP (1988) Synovial fluid T cell reactivity against 65 kD heat shock protein of mycobacteria in early chronic arthritis. The Lancet 332:478–480

    Article  Google Scholar 

  • Brown JP, Jean G (2016) Does Epstein-Barr virus infection contribute to disease flares in rheumatoid arthritis. J Arthritis 5:208

    Article  Google Scholar 

  • Cantley MD, Haynes DR, Marino V, Bartold PM (2011) Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. J Clin Periodontol 38:532–541

    Article  PubMed  Google Scholar 

  • Ceccarelli F, Orrù G, Pilloni A, Bartosiewicz I, Perricone C, Martino E, Lucchetti R, Fais S, Vomero M, Olivieri M (2018) Porphyromonas gingivalis in the tongue biofilm is associated with clinical outcome in rheumatoid arthritis patients. Clin Exp Immunol 194:244–252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Celis L, Vandevyver C, Geusens P, Dequeker J, Raus J, Zhang J (1997) Clonal expansion of mycobacterial heat-shock protein–reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients. Arthritis Rheum 40:510–519

    Article  CAS  PubMed  Google Scholar 

  • Christopoulos G, Christopoulou V, Routsias J, Babionitakis A, Antoniadis C, Vaiopoulos G (2017) Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis. Clin Rheumatol 36:527–535

    Article  PubMed  Google Scholar 

  • Costenbader KH, Karlson EW (2006) Epstein-Barr virus and rheumatoid arthritis: is there a link? Arthritis Res Ther 8:1–7

    Article  Google Scholar 

  • Cronan MR, Beerman RW, Rosenberg AF, Saelens JW, Johnson MG, Oehlers SH, Sisk DM, Smith KLJ, Medvitz NA, Miller SE (2016) Macrophage epithelial reprogramming underlies mycobacterial granuloma formation and promotes infection. Immunity 45:861–876

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cross M, Smith E, Hoy D, Carmona L, Wolfe F, Vos T, Williams B, Gabriel S, Lassere M, Johns N (2014) The global burden of rheumatoid arthritis: estimates from the global burden of disease 2010 study. Ann Rheum Dis 73:1316–1322

    Article  PubMed  Google Scholar 

  • Darrah E, Andrade F (2018) Rheumatoid arthritis and citrullination. Curr Opin Rheumatol 30:72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • De Pablo P, Dietrich T, McAlindon TE (2008) Association of periodontal disease and tooth loss with rheumatoid arthritis in the US population. J Rheumatol 35:70–76

    PubMed  Google Scholar 

  • de Smit M, Westra J, Vissink A, Doornbos-van der Meer B, Brouwer E, van Winkelhoff AJ (2012) Periodontitis in established rheumatoid arthritis patients: a cross-sectional clinical, microbiological and serological study. Arthritis Res Ther 14:1–10

    Article  Google Scholar 

  • Deane KD, Demoruelle MK, Kelmenson LB, Kuhn KA, Norris JM, Holers VM (2017) Genetic and environmental risk factors for rheumatoid arthritis. Best Pract Res Clin Rheumatol 31:3–18

    Article  PubMed  PubMed Central  Google Scholar 

  • Demmer RT, Molitor JA, Jacobs DR Jr, Michalowicz BS (2011) Periodontal disease, tooth loss and incident rheumatoid arthritis: results from the First National Health and Nutrition Examination Survey and its epidemiological follow-up study. J Clin Periodontol 38:998–1006

    Article  PubMed  PubMed Central  Google Scholar 

  • Dissick A, Redman RS, Jones M, Rangan BV, Reimold A, Griffiths GR, Mikuls TR, Amdur RL, Richards JS, Kerr GS (2010) Association of periodontitis with rheumatoid arthritis: a pilot study. J Clin Periodontol 81:223–230

    Article  Google Scholar 

  • Dos Anjos LME, Pereira IA, d’Orsi E, Seaman AP, Burlingame RW, Morato EF (2009) A comparative study of IgG second-and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis. Clin Rheumatol 28:153

    Article  PubMed  Google Scholar 

  • Dow CT (2012) M. paratuberculosis heat shock protein 65 and human diseases: bridging infection and autoimmunity. Autoimmun Dis 2012

  • Drago L (2019) Prevotella Copri and Microbiota in Rheumatoid Arthritis: Fully Convincing Evidence? J Clin Med 8

  • Dubaniewicz A, Dubaniewicz-Wybieralska M, Sternau A, Zwolska Z, Izycka-Swieszewska E, Augustynowicz-Kopec E, Skokowski J, Singh M, Zimnoch L (2006a) Mycobacterium tuberculosis complex and mycobacterial heat shock proteins in lymph node tissue from patients with pulmonary sarcoidosis. J Clin Microbiol 44:3448–3451

    Article  PubMed  PubMed Central  Google Scholar 

  • Dubaniewicz A, Trzonkowski P, Dubaniewicz-Wybieralska M, Dubaniewicz A, Singh M, Myśliwski A (2006b) Comparative analysis of mycobacterial heat shock proteins-induced apoptosis of peripheral blood mononuclear cells in sarcoidosis and tuberculosis. J Clin Immunol 26:243–250

    Article  PubMed  Google Scholar 

  • Dutertre M, Delobel P, Marchou B, Boyer J-F, Mougari F, Martin-Blondel G (2019) Olecranon bursitis secondary to Mycobacterium europaeum infection in a patient receiving immunosuppressive drugs for rheumatoid arthritis. Med Mal Infect 49:358–359

    Article  PubMed  Google Scholar 

  • Ebringer A, Rashid T (2006) Rheumatoid arthritis is an autoimmune disease triggered by Proteus urinary tract infection. Clin Dev Immunol 13:41–48

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebringer A, Rashid T (2014) Rheumatoid arthritis is caused by a Proteus urinary tract infection. APMIS 122:363–368

    Article  CAS  PubMed  Google Scholar 

  • Ebringer A, Rashid T, Wilson C (2010) Rheumatoid arthritis, Proteus, anti-CCP antibodies and Karl Popper. Autoimmun Rev 9:216–223

    Article  CAS  PubMed  Google Scholar 

  • Elkayam O, Segal R, Bendayan D, van Uitert R, Onnekink C, Pruijn GJ (2010) The anti-cyclic citrullinated peptide response in tuberculosis patients is not citrulline-dependent and sensitive to treatment. Arthritis Res Ther 12:1–7

    Article  Google Scholar 

  • Erre GL, Cossu D, Masala S, Mameli G, Cadoni M, Serdino S, Longu MG, Passiu G, Sechi LA (2014) Mycobacterium tuberculosis lipoarabinomannan antibodies are associated to rheumatoid arthritis in Sardinian patients. Clin Rheumatol 33:1725–1729

    Article  CAS  PubMed  Google Scholar 

  • Esaguy N, Aguas AP, Van Embden J, Silva MT (1991) Mycobacteria and human autoimmune disease: direct evidence of cross-reactivity between human lactoferrin and the 65-kilodalton protein of tubercle and leprosy bacilli. Infect Immun 59:1117–1125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fairley K, Carson N, Gutch RC, Leighton P, Grounds A, Laird E, McCallum P, Sleeman R, O’Keefe C (1971) Site of infection in acute urinary-tract infection in general practice. The Lancet 298:615–618

    Article  Google Scholar 

  • Farrugia M, Baron B (2016) The role of TNF-α in rheumatoid arthritis: A focus on regulatory T cells. J Clin Transl Res 2:84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fattahi A, Lotfali E, Masoumi-Asl H, Sayyahfar S, Kalani M, Khourgami MR, Yassin Z (2020) Candidemia and its risk factors in neonates and children. Arch Pediatr Infect Dis 8:1–5

    Article  Google Scholar 

  • Ford DK, Roza DMD, Schulzer M, Reid GD, Denegri JF (1987) Persistent synovial lymphocyte responses to cytomegalovirus antigen in some patients with rheumatoid arthritis. Arthritis Rheum 30:700–704

    Article  CAS  PubMed  Google Scholar 

  • Fuggle NR, Smith TO, Kaul A, Sofat N (2016) Hand to mouth: a systematic review and meta-analysis of the association between rheumatoid arthritis and periodontitis. Front Immunol 7:80

    Article  PubMed  PubMed Central  Google Scholar 

  • Gagneux S (2018) Ecology and evolution of Mycobacterium tuberculosis. Nat Rev Microbiol 16:202–213

    Article  CAS  PubMed  Google Scholar 

  • Gómez-Bañuelos E, Mukherjee A, Darrah E, Andrade F (2019) Rheumatoid arthritis-associated mechanisms of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. J Clin Med 8:1309

    Article  PubMed  PubMed Central  Google Scholar 

  • Gray A, Guillou L, Zufferey J, Rey F, Kurt A-M, Jichlinski P, Leisinger H-J, Benhattar J (1998) Persistence of parvovirus B19 DNA in testis of patients with testicular germ cell tumours. J Gen Virol 79:573–579

    Article  CAS  PubMed  Google Scholar 

  • Harvey G, Fitzsimmons T, Dhamarpatni A, Marchant C, Haynes D, Bartold P (2013) Expression of peptidylarginine deiminase-2 and-4, citrullinated proteins and anti-citrullinated protein antibodies in human gingiva. J Periodontal Res 48:252–261

    Article  CAS  PubMed  Google Scholar 

  • Henderson B, Ward JM, Ready D (2010) Aggregatibacter (Actinobacillus) actinomycetemcomitans: a triple A* periodontopathogen? Periodontol 2000 54:78–105

    Article  PubMed  Google Scholar 

  • Hezarjaribi HZ, Azadeh H, Niksolat F, Montazeri M, Tabaripour R, Fakhar M, Hosseintabar M, Keighobadi M, Nakhaei M (2021) Toxoplasma gondii infection in patients with rheumatoid arthritis and systemic lupus erythematous diseases: serological and molecular evidence. Ann Parasitol 67:223–228

    PubMed  Google Scholar 

  • Hitchon CA, Chandad F, Ferucci ED, Willemze A, Ioan-Facsinay A, van der Woude D, Markland J, Robinson D, Elias B, Newkirk M (2010) Antibodies to Porphyromonas gingivalis are associated with anticitrullinated protein antibodies in patients with rheumatoid arthritis and their relatives. J Rheumatol 37:1105–1112

    Article  CAS  PubMed  Google Scholar 

  • Holoshttz J, Strober S, Koning F, Coligan JE, De Bruyn J (1989) Isolation of CD4-CD8-mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature 339:226–229

    Article  Google Scholar 

  • Hooton TM (2012) Uncomplicated urinary tract infection. N Engl J Med 366:1028–1037

    Article  CAS  PubMed  Google Scholar 

  • Hsiao FC, Lin M, Tai A, Chen G, Huber BT (2006) Cutting edge: Epstein-Barr virus transactivates the HERV-K18 superantigen by docking to the human complement receptor 2 (CD21) on primary B cells. J Immunol 177:2056–2060

    Article  CAS  PubMed  Google Scholar 

  • Hussain M, Stover CM, Dupont A (2015) P. gingivalis in periodontal disease and atherosclerosis–scenes of action for antimicrobial peptides and complement. Front Immunol 6:45

  • Hussein HM, Rahal EA (2019) The role of viral infections in the development of autoimmune diseases. Crit Rev Microbiol 45:394–412

    Article  CAS  PubMed  Google Scholar 

  • Ingraham NE, Schneider B, Alpern JD (2017) Prosthetic joint infection due to Mycobacterium avium-intracellulare in a patient with rheumatoid arthritis: a case report and review of the literature. Int J Infect Dis 2017

  • Jamil RT, Foris LA, Snowden J (2017) Proteus mirabilis infections

  • Johansson L, Sherina N, Kharlamova N, Potempa B, Larsson B, Israelsson L, Potempa J, Rantapää-Dahlqvist S, Lundberg K (2016) Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther 18:1–10

    Google Scholar 

  • Joseph R, Raj MJ, Sundareswaran S, Kaushik PC, Nagrale AV, Jose S, Rajappan S (2014) Does a biological link exist between periodontitis and rheumatoid arthritis? World 3

  • Julia A, Marsal S (2013) The genetic architecture of rheumatoid arthritis: from susceptibility to clinical subphenotype associations. Curr Top Med Chem 13:720–731

    Article  CAS  PubMed  Google Scholar 

  • Kempsell KE, Cox CJ, McColm AA, Bagshaw JA, Reece R, Veale DJ, Emery P, Isaacs JD, Gaston JH, Crowe JS (2001) Detection of Mycobacterium tuberculosis group organisms in human and mouse joint tissue by reverse transcriptase PCR: prevalence in diseased synovial tissue suggests lack of specific association with rheumatoid arthritis. Infect Immun 69:1821–1831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Klatt T, Ouyang Q, Flad T, Koetter I, Bühring H-J, Kalbacher H, Pawelec G, Müller CA (2005) Expansion of peripheral CD8+ CD28-T cells in response to Epstein-Barr virus in patients with rheumatoid arthritis. J Rheumatol 32:239–251

    CAS  PubMed  Google Scholar 

  • Kogure A, Miyata M, Nishimaki T, Kasukawa R (1994) Proliferative response of synovial fluid mononuclear cells of patients with rheumatoid arthritis to mycobacterial 65 kDa heat shock protein and its association with HLA-DR+. gamma delta+ T cells. J Rheumatol 21:1403–1408

    CAS  PubMed  Google Scholar 

  • Konig MF, Abusleme L, Reinholdt J, Palmer RJ, Teles RP, Sampson K, Rosen A, Nigrovic PA, Sokolove J, Giles JT (2016) Aggregatibacter actinomycetemcomitans–induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176–369ra176

  • Koziel J, Mydel P, Potempa J (2014) The link between periodontal disease and rheumatoid arthritis: an updated review. Curr Rheumatol Rep 16:408

    Article  PubMed  PubMed Central  Google Scholar 

  • Lim M-K, Shim TS, Sheen D-H, Na D-J, Min SS, Shim S-C (2010) Anti-cyclic citrulline peptide antibody in non-tuberculous mycobacteria sera: a negative association. Clin Rheumatol 29:335–336

    Article  PubMed  Google Scholar 

  • Listing J, Gerhold K, Zink A (2013) The risk of infections associated with rheumatoid arthritis, with its comorbidity and treatment. Rheumatology 52:53–61

    Article  CAS  PubMed  Google Scholar 

  • Luban S, LI ZG (2010) Citrullinated peptide and its relevance to rheumatoid arthritis: an update. Int J Rheum Dis 13:284–287

    Article  PubMed  Google Scholar 

  • Lundberg K, Kinloch A, Fisher BA, Wegner N, Wait R, Charles P, Mikuls TR, Venables PJ (2008) Antibodies to citrullinated α-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum 58:3009–3019

    Article  CAS  PubMed  Google Scholar 

  • Lünemann JD, Frey O, Eidner T, Baier M, Roberts S, Sashihara J, Volkmer R, Cohen JI, Hein G, Kamradt T (2008) Increased frequency of EBV-specific effector memory CD8+ T cells correlates with higher viral load in rheumatoid arthritis. J Immunol 181:991–1000

    Article  PubMed  Google Scholar 

  • Lutteri L, Malaise M, Chapelle J-P (2007) Comparison of second-and third-generation anti-cyclic citrullinated peptide antibodies assays for detecting rheumatoid arthritis. Clin Chim Acta 386:76–81

    Article  CAS  PubMed  Google Scholar 

  • Ma X, Xu S (2013) TNF inhibitor therapy for rheumatoid arthritis. Biomed Rep 1:177–184

    Article  CAS  PubMed  Google Scholar 

  • MacGregor AJ, Snieder H, Rigby AS, Koskenvuo M, Kaprio J, Aho K, Silman AJ (2000) Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 43:30–37

    Article  CAS  PubMed  Google Scholar 

  • Martinez-Martinez RE, Abud-Mendoza C, Patiño-Marin N, Rizo-Rodríguez JC, Little JW, Loyola-Rodríguez JP (2009) Detection of periodontal bacterial DNA in serum and synovial fluid in refractory rheumatoid arthritis patients. J Clin Periodontol 36:1004–1010

    Article  CAS  PubMed  Google Scholar 

  • Masson-Bessière C, Sebbag M, Girbal-Neuhauser E, Nogueira L, Vincent C, Senshu T, Serre G (2001) The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the α-and β-chains of fibrin. J Immunol 166:4177–4184

    Article  PubMed  Google Scholar 

  • McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365:2205–2219

    Article  CAS  PubMed  Google Scholar 

  • Mehraein Y, Lennerz C, Ehlhardt S, Remberger K, Ojak A, Zang KD (2004) Latent Epstein-Barr virus (EBV) infection and cytomegalovirus (CMV) infection in synovial tissue of autoimmune chronic arthritis determined by RNA-and DNA-in situ hybridization. Mod Pathol 17:781–789

    Article  CAS  PubMed  Google Scholar 

  • Mehta B, Pedro S, Ozen G, Kalil A, Wolfe F, Mikuls T, Michaud K (2019) Serious infection risk in rheumatoid arthritis compared with non-inflammatory rheumatic and musculoskeletal diseases: a US national cohort study. RMD Open 5:e000935

    Article  PubMed  PubMed Central  Google Scholar 

  • Meyer DH, Fives-Taylor PM (1997) The role of Actinobacillus actinomycetemcomitans in the pathogenesis of periodontal disease. Trends Microbiol 5:224–228

    Article  CAS  PubMed  Google Scholar 

  • Mikuls TR, Payne JB, Reinhardt RA, Thiele GM, Maziarz E, Cannella AC, Holers VM, Kuhn KA, O’Dell JR (2009) Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid arthritis and periodontitis. Int Immunopharmacol 9:38–42

    Article  CAS  PubMed  Google Scholar 

  • Mikuls TR, Thiele GM, Deane KD, Payne JB, O’Dell JR, Yu F, Sayles H, Weisman MH, Gregersen PK, Buckner JH (2012) Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis. Arthritis Rheum 64:3522–3530

    Article  CAS  PubMed  Google Scholar 

  • Monteiro AC, Scovino A, Raposo S, Gaze VM, Cruz C, Svensjö E, Narciso MS, Colombo AP, Pesquero JB, Feres-Filho E (2009) Kinin danger signals proteolytically released by gingipain induce Fimbriae-specific IFN-γ-and IL-17-producing T cells in mice infected intramucosally with Porphyromonas gingivalis. J Immunol 183:3700–3711

    Article  CAS  PubMed  Google Scholar 

  • Newkirk M, Duffy KW, Leclerc J, Lambert N, Shiroky J (1994) Detection of cytomegalovirus, Epstein-Barr virus and herpes virus-6 in patients with rheumatoid arthritis with or without Sjögren’s syndrome. Rheumatology 33:317–322

    Article  CAS  Google Scholar 

  • Newkirk M, Goldbach-Mansky R, Senior B, Klippel J, Schumacher H Jr, El-Gabalawy H (2005) Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis. Rheumatology 44:1433–1441

    Article  CAS  PubMed  Google Scholar 

  • Nicaise-Roland P, Nogueira L, Demattei C, de Chaisemartin L, Rincheval N, Cornillet M, Grootenboer-Mignot S, Dieudé P, Dougados M, Cantagrel A (2013) Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies in diagnosing rheumatoid arthritis at an early stage: data from the French ESPOIR cohort. Ann Rheum Dis 72:357–362

    Article  PubMed  Google Scholar 

  • Ogrendik M (2009) Rheumatoid arthritis is linked to oral bacteria: etiological association. Mod Rheumatol 19:453–456

    Article  PubMed  Google Scholar 

  • Ogrendik M (2013) Rheumatoid arthritis is an autoimmune disease caused by periodontal pathogens. Int J Gen Med 6:383

    Article  PubMed  PubMed Central  Google Scholar 

  • Omidi N, Kashani BS, Piranfar MA, Khorgami MR, Yekta BG, Omidi H (2012) The correlation of diastolic dysfunction with TIMI frame count in patients with chronic stable angina pectoris. Tehran Univ Med J 70

  • Page C, François C, Goëb V, Duverlie G (2015) Human parvovirus B19 and autoimmune diseases. Review of the literature and pathophysiological hypotheses. J Clin Virol 72:69–74

    Article  CAS  PubMed  Google Scholar 

  • Pan Z-Y, Zhong H-J, Huang D-N, Wu L-H, He X-X (2022) Beneficial effects of repeated washed microbiota transplantation in children with autism. Front Pediatr 971

  • Payne JB, Golub LM, Thiele GM, Mikuls TR (2015) The link between periodontitis and rheumatoid arthritis: a periodontist’s perspective. Curr Oral Health Rep 2:20–29

    Article  PubMed  Google Scholar 

  • Pianta A, Arvikar S, Strle K, Drouin EE, Wang Q, Costello CE, Steere AC (2017) Evidence of the immune relevance of Prevotella copri, a gut microbe, in patients with rheumatoid arthritis. Arthritis Rheumatol 69:964–975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal Diseases the Lancet 366:1809–1820

    Google Scholar 

  • Puntis D, Malik S, Saravanan V, Rynne M, Heycock C, Hamilton J, Kelly C (2013) Urinary tract infections in patients with rheumatoid arthritis. Clin Rheumatol 32:355–360

    Article  CAS  PubMed  Google Scholar 

  • Rajabinejad M, Lotfi R, Roghani SA, Koolani E, Soleymani B, Rezaiemanesh A, Mohamadi Kish Z, Halashi B, Khorasanizadeh A, Shaveisizadeh Z (2021) Difference in the Cytomegalovirus-related clinical laboratory findings between patients with bone marrow and kidney transplantation. Res Mol Med 9:0–0

  • Rashid T, Jayakumar K, Binder A, Ellis S, Cunningham P, Ebringer A (2007) Rheumatoid arthritis patients have elevated antibodies to cross-reactive and non cross-reactive antigens from Proteus microbes. Clin Exp Rheumatol 25:259

    CAS  PubMed  Google Scholar 

  • Ribeiro F, Szyper-Kravitz M, Klumb E, Lannes G, Ribeiro F, Albuquerque E, Shoenfeld Y (2010) Can lupus flares be associated with tuberculosis infection? Clin Rev Allergy Immunol 38:163–168

    Article  CAS  PubMed  Google Scholar 

  • Rickinson AB, Moss DJ (1997) Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection. Ann Rev Immunol 15:405–431

    Article  CAS  Google Scholar 

  • Röhner E, Detert J, Kolar P, Hocke A, N’Guessan P, Matziolis G, Kanitz V, Bernimoulin J, Kielbassa A, Burmester G (2010) Induced apoptosis of chondrocytes by Porphyromonas gingivalis as a possible pathway for cartilage loss in rheumatoid arthritis. Calcif Tissue Int 87:333–340

    Article  PubMed  Google Scholar 

  • Rook G (1988) Rheumatoid arthritis, mycobacterial antigens and agalactosyl IgG. Scand J Immunol 28:487–493

    Article  CAS  PubMed  Google Scholar 

  • Rosser EC, Mauri C (2016) A clinical update on the significance of the gut microbiota in systemic autoimmunity. J Autoimmun 74:85–93

    Article  CAS  PubMed  Google Scholar 

  • RoUDIER J, Petersen J, Rhodes GH, Luka J, Carson DA (1989) Susceptibility to rheumatoid arthritis maps to a T-cell epitope shared by the HLA-Dw4 DR beta-1 chain and the Epstein-Barr virus glycoprotein gp110. Proc Natl Acad Sci 86:5104–5108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saal J, Steidle M, Einsele H, Müller C, Fritz P, Zacher J (1992) Persistence of B19 parvovirus in synovial membranes of patients with rheumatoid arthritis. Rheumatol Int 12:147–151

    Article  CAS  PubMed  Google Scholar 

  • Salloum N, Hussein HM, Jammaz R, Jiche S, Uthman IW, Abdelnoor AM, Rahal EA (2018) Epstein-Barr virus DNA modulates regulatory T-cell programming in addition to enhancing interleukin-17A production via Toll-like receptor 9. PLoS ONE 13:e0200546

    Article  PubMed  PubMed Central  Google Scholar 

  • Salvetti M, Ristori G, Buttinelli C, Fiori P, Falcone M, Britton W, Adams E, Paone G, Grasso MG, Pozzilli C (1996) The immune response to mycobacterial 70-kDa heat shock proteins frequently involves autoreactive T cells and is quantitatively disregulated in multiple sclerosis. J Neuroimmunol 65:143–153

    Article  CAS  PubMed  Google Scholar 

  • Sanmartí R, Graell E, Perez ML, Ercilla G, Viñas O, Gómez-Puerta JA, Gratacós J, Balsa A, Gómara MJ, Larrosa M (2009) Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis. Arthritis Res Ther 11:1–9

    Article  Google Scholar 

  • Sasaki T (2007) Human parvovirus B19 and rheumatoid arthritis

  • Schellekens GA, De Jong B, Van den Hoogen F, Van de Putte L, van Venrooij WJ (1998) Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest 101:273–281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schellekens GA, Visser H, De Jong BA, Van Den Hoogen FH, Hazes JM, Breedveld FC, Van Venrooij WJ (2000) The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 43:155–163

    Article  CAS  PubMed  Google Scholar 

  • Scotet E, David-Ameline J, Peyrat M-A, Moreau-Aubry A, Pinczon D, Lim A, Even J, Semana G, Berthelot J-M, Breathnach R (1996) T cell response to Epstein-Barr virus transactivators in chronic rheumatoid arthritis. Int J Clin Exp Med 184:1791–1800

    CAS  Google Scholar 

  • Seifert JA, Bemis EA, Ramsden K, Lowell C, Polinski K, Feser M, Fleischer C, Demoruelle MK, Buckner J, Gregersen PK, Keating RM, Mikuls TR, O'Dell JR, Weisman MH, Deane KD, Norris JM, Steere AC, Holers VM (2022) Association of antibodies to Prevotella copri in anti-CCP-positive individuals at-risk for developing rheumatoid arthritis and in those with early or established rheumatoid arthritis. Arthritis Rheumatol

  • Shehab M, Sherri N, Hussein H, Salloum N, Rahal EA (2019) Endosomal toll-like receptors mediate enhancement of interleukin-17a production triggered by Epstein-Barr virus DNA in mice. J Virol 93:e00987-e1919

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shoda H, Hanata N, Sumitomo S, Okamura T, Fujio K, Yamamoto K (2016) Immune responses to Mycobacterial heat shock protein 70 accompany self-reactivity to human BiP in rheumatoid arthritis. Sci Rep 6:1–10

    Article  Google Scholar 

  • Smatti MK, Al-Sadeq DW, Ali NH, Pintus G, Abou-Saleh H, Nasrallah GK (2018) Epstein-Barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: an update. Front Oncol 8:211

    Article  PubMed  PubMed Central  Google Scholar 

  • Söderlund M, von Essen R, Haapasaari J, Kiistala U, Kiviluoto O, Hedman K (1997) Persistence of parvovirus B19 DNA in synovial membranes of young patients with and without chronic arthropathy. The Lancet 349:1063–1065

    Article  Google Scholar 

  • Solovic I, Sester M, Gomez-Reino JJ, Rieder HL, Ehlers S, Milburn HJ, Kampmann B, Hellmich B, Groves R, Schreiber S (2010) The risk of tuberculosis related to tumour necrosis factor antagonist therapies: a TBNET consensus statement. Eur Respiratory Soc

  • Stoll ML (2020) Genetics, Prevotella, and the pathogenesis of rheumatoid arthritis. Lancet Rheumatol 2:e375–e376

    Article  Google Scholar 

  • Takahashi Y, Murai C, Shibata S, Munakata Y, Ishii T, Ishii K, Saitoh T, Sawai T, Sugamura K, Sasaki T (1998) Human parvovirus B19 as a causative agent for rheumatoid arthritis. Proc Natl Acad Sci 95:8227–8232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Takeda T, Mizugaki Y, Matsubara L, Imai S, Koike T, Takada K (2000) Lytic Epstein-Barr virus infection in the synovial tissue of patients with rheumatoid arthritis. Arthritis Rheum 43:1218–1225

    Article  CAS  PubMed  Google Scholar 

  • Tani Y, Tiwana H, Hukuda S, Nishioka J, Fielder M, Wilson C, Bansal S, Ebringer A (1997) Antibodies to Klebsiella, Proteus, and HLA-B27 peptides in Japanese patients with ankylosing spondylitis and rheumatoid arthritis. J Rheumatol 24:109–114

    CAS  PubMed  Google Scholar 

  • Tiwana H, Wilson C, Alvarez A, Abuknesha R, Bansal S, Ebringer A (1999) Cross-reactivity between the rheumatoid arthritis-associated motif EQKRAA and structurally related sequences found in Proteus mirabilis. Infect Immun 67:2769–2775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tsuchiya N, Williams R Jr (1992) Molecular mimicry–hypothesis or reality? West J Med 157:133

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tzang B-S, Tsai C-C, Tsay GJ, Wang M, Sun Y-S, Hsu T-C (2009) Anti-human parvovirus B19 nonstructural protein antibodies in patients with rheumatoid arthritis. Clin Chim Acta 405:76–82

    Article  CAS  PubMed  Google Scholar 

  • Vafaei S, Mirnejad R, Amirmozafari N (2013) Determining the patterns of antimicrobial susceptibility and the distribution of blaCTX-M genes in strains of Acinetobacter Baumannii isolated from clinical samples. J Isfahan Med 31:1443–1451

    Google Scholar 

  • Valesini G, Gerardi MC, Iannuccelli C, Pacucci VA, Pendolino M, Shoenfeld Y (2015) Citrullination and autoimmunity. Autoimmun Rev 14:490–497

    Article  CAS  PubMed  Google Scholar 

  • van der Meulen TA, Harmsen HJ, Bootsma H, Spijkervet FK, Kroese FG, Vissink A (2016) The microbiome–systemic diseases connection. Oral Dis 22:719–734

    Article  PubMed  Google Scholar 

  • Van Eden W, Holoshitz J, Nevo Z, Frenkel A, Klajman A, Cohen IR (1985) Arthritis induced by a T-lymphocyte clone that responds to Mycobacterium tuberculosis and to cartilage proteoglycans. Proc Natl Acad Sci 82:5117–5120

    Article  PubMed  PubMed Central  Google Scholar 

  • van Eden W, Tholet JE, van der Zee R, Noordzij A, van Embden JD, Hensen EJ, Cohen IR (1988) Cloning of the mycobacterial epitope recognized by T lymphocytes in adjuvant arthritis. Nature 331:171–173

    Article  PubMed  Google Scholar 

  • Velusamy SK, Sampathkumar V, Godboley D, Fine DH (2016) Profound effects of Aggregatibacter actinomycetemcomitans leukotoxin mutation on adherence properties are clarified in in vitro experiments. PLoS ONE 11:e0151361

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang H, Gao Y, Vafaei S, Yu Q, Zhang J, Wang L (2022) A chemoresistance lncRNA signature for recurrence risk stratification of colon cancer patients with chemotherapy. Mol Ther Nucleic Acids 27:427–438

    Article  CAS  PubMed  Google Scholar 

  • Wasfi R, Hamed SM, Abd Allah MAW, Ismail L (2020) Proteus mirabilis biofilm: development and therapeutic strategies. Front Cell Infect Microbiol 10:414

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K, Kinloch A, Culshaw S, Potempa J, Venables PJ (2010) Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis. Arthritis Rheum 62:2662–2672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson C, Ebringer A, Ahmadi K, Wrigglesworth J, Tiwana H, Fielder M, Binder A, Ettelaie C, Cunningham P, Joannou C (1995) Shared amino acid sequences between major histocompatibility complex class II glycoproteins, type XI collagen and Proteus mirabilis in rheumatoid arthritis. Ann Rheum Dis 54:216–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wilson C, Rashid T, Ebringer A (2015) Worldwide links between Proteus mirabilis and rheumatoid arthritis. J Arthritis 4:1000142

    Google Scholar 

  • Wucherpfennig KW, Strominger JL (1995) Molecular mimicry in T cell-mediated autoimmunity: viral peptides activate human T cell clones specific for myelin basic protein. Cell 80:695–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarean M, Mastroeni P, Moghaddas E, Farash BRH, Raouf-Rahmati A, Jamali J, Azadeh H, Kam V (2022) Toxoplasmosis frequency rate in rheumatoid arthritis patients in Northeastern Iran. Iran J Parasitol 17:325–331

    PubMed  PubMed Central  Google Scholar 

  • Zhang L, Nikkari S, Skurnik M, Ziegler T, Luukkainen R, Möttönen T, Toivanen P (1993) Detection of herpesviruses by polymerase chain reaction in lymphocytes from patients with rheumatoid arthritis. Arthritis Rheum 36:1080–1086

    Article  CAS  PubMed  Google Scholar 

  • Zügel U, Kaufmann SH (1999) Role of heat shock proteins in protection from and pathogenesis of infectious diseases. Clin Microbiol Rev 12:19–39

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics Rheumatology, Ali Asghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran

    Shima Salehi

  2. Emergency Medicine Management Research Center, Ali Asghar Children Hospital, Iran University of Medical Sciences, Tehran, Iran

    Seyedeh Mahsa Mahmoudinezhad Dezfouli & Shaqayeq Khosravi

  3. Department of Internal Medicine, Rheumatology Division, Orthopedic Research Center, Mazandaran University of Medical Sciences, Sari, Iran

    Hossein Azadeh

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  1. Shima Salehi
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  2. Seyedeh Mahsa Mahmoudinezhad Dezfouli
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SM. M and Sh. Kh. contributed to the idea design, literature search, and manuscript writing. Sh. S. contributed to designing the figures. H. A. performed the manuscript’s final revision.

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Salehi, S., Mahmoudinezhad Dezfouli, S.M., Azadeh, H. et al. Immune dysregulation and pathogenic pathways mediated by common infections in rheumatoid arthritis. Folia Microbiol 68, 325–335 (2023). https://doi.org/10.1007/s12223-023-01036-0

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