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Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study

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Abstract

Objective

To establish the association between adipokine levels and markers of periodontal involvement as risk indicators of early stages of RA (eRA) and the interaction between the presence of markers of periodontal disease with adipokine in eRA individuals.

Materials and methods

Fifty-one patients with a diagnosis of eRA and 51 healthy controls matched for age and sex were studied. Clinical joint condition, clinical and serological markers of disease activity, serum adipokine levels (leptin, adiponectin, resistin, adipsin, vaspin, and IL-6), periodontal diagnosis, presence of Porphyromonas gingivalis, and related IgG1 and IgG2 antibodies were evaluated. Comparisons were made between eRA and healthy controls for periodontal indicators and adipokines. A subgroup analysis was realized with a non-conditional logistic regression to establish the association between the levels of leptin in individuals with eRA and controls according to the periodontal condition, presence of P. gingivalis, or high titers of IgG antibodies against P. gingivalis.

Results

The condition of overweight or obesity is associated with the diagnosis of eRA (p = 0.05), and these individuals also have higher levels of leptin (p = 0.001) and vaspin (p = 0.007). Higher frequency of P. gingivalis (p = 0.001) was found in the eRa group. Individuals with eRA with higher IgG2 titers against P. gingivalis had higher levels of leptin (OR: 1.66 (CI 95% 1.01–2.73)); however, individuals with periodontitis or P. gingivalis with eRA were associated with highest levels of leptin (OR: 1.86, CI 95% 1.19–24.3; and OR: 2.04, CI 95% 1.37–3 respectively).

Conclusions

eRA individuals have high levels of leptin and vaspin. However, the presence of periodontitis and related-periodontal disease markers showed an effect only in leptin levels in eRA individuals.

Clinical relevance

Emphasizing in personalized medicine, monitoring serum leptin levels and periodontitis markers can improve the early diagnosis of RA.

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References

  1. Angelotti F, Parma A, Cafaro G, Capecchi R, Alunno A, Puxeddu I (2017) One year in review 2017: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol 35(3):368–378

    PubMed  Google Scholar 

  2. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, Flemmig TF, Garcia R, Giannobile WV, Graziani F, Greenwell H, Herrera D, Kao RT, Kebschull M, Kinane DF, Kirkwood KL, Kocher T, Kornman KS, Kumar PS, Loos BG, Machtei E, Meng H, Mombelli A, Needleman I, Offenbacher S, Seymour GJ, Teles R, Tonetti MS (2018) Periodontitis: consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol 89:S173–S182

    PubMed  Google Scholar 

  3. Wegner N, Wait R, Sroka A, Eick S, Nguyen K-A, 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(9):2662–2672

    PubMed  PubMed Central  Google Scholar 

  4. Lundberg K, Wegner N, Yucel-Lindberg T, Venables PJ (2010) Periodontitis in RA—the citrullinated enolase connection. Nat Rev Rheumatol 6(12):727–730

    PubMed  Google Scholar 

  5. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11(2):85–97

    PubMed  PubMed Central  Google Scholar 

  6. Alvarez-Nemegyei J, Pacheco-Pantoja E, González-Salazar M, López-Villanueva RF, May-Kim S, Martínez-Vargas L, et al. (2018) Association between overweight/obesity and clinical activity in rheumatoid arthritis. Reumatol Clin;S1699-258X(18):30257–2

  7. Jepsen S, Caton JG, Albandar JM, Bissada NF, Bouchard P, Cortellini P, Demirel K, de Sanctis M, Ercoli C, Fan J, Geurs NC, Hughes FJ, Jin L, Kantarci A, Lalla E, Madianos PN, Matthews D, McGuire MK, Mills MP, Preshaw PM, Reynolds MA, Sculean A, Susin C, West NX, Yamazaki K (2018) Periodontal manifestations of systemic diseases and developmental and acquired conditions: consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol 89:S237–S248

    PubMed  Google Scholar 

  8. Finckh A, Turesson C (2014) The impact of obesity on the development and progression of rheumatoid arthritis. Ann Rheum Dis 73(11):1911–1913

    PubMed  Google Scholar 

  9. Engström M, Eriksson K, Lee L, Hermansson M, Johansson A, Nicholas AP et al (2018) Increased citrullination and expression of peptidylarginine deiminases independently of P. gingivalis and A. actinomycetemcomitans in gingival tissue of patients with periodontitis. J Transl Med 16(1):214

    PubMed  PubMed Central  Google Scholar 

  10. Zhu J, Guo B, Gan X, Zhang L, He Y, Liu B, Chen X, Zhang S, Yu H (2017) Association of circulating leptin and adiponectin with periodontitis: a systematic review and meta-analysis. BMC Oral Health 17(1):104

    PubMed  PubMed Central  Google Scholar 

  11. Akram Z, Abduljabbar T, Abu Hassan MI, Javed F, Vohra F (2016) Cytokine profile in chronic periodontitis patients with and without obesity: a systematic review and meta-analysis. Dis Markers 2016:1–12

    Google Scholar 

  12. Chaparro-Sanabria J, Bautista-Molano W, Bello-Gualtero J, Chila-Moreno L, Castillo D, Valle-Oñate R, et al. (2019) Association of adipokines with rheumatic disease activity indexes and periodontal disease in patients with early rheumatoid arthritis and first-degree relatives of patients with rheumatoid arthritis ;1–14

  13. Bodet C, Chandad F, Grenier D (2006) Inflammatory responses of a macrophage/epithelial cell co-culture model to mono and mixed infections with Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Microbes Infect 8(1):27–35

    PubMed  Google Scholar 

  14. Imatani T, Kato T, Okuda K (2001) Production of inflammatory cytokines by human gingival fibroblasts stimulated by cell-surface preparations of Porphyromonas gingivalis. Oral Microbiol Immunol 16(2):65–72

    PubMed  Google Scholar 

  15. Shi D, Liu Y-Y, Li W, Zhang X, Sun X-J, Xu L, Zhang L, Chen ZB, Meng HX (2015) Association between plasma leptin level and systemic inflammatory markers in patients with aggressive periodontitis. Chin Med J 128(4):528–532

    PubMed  PubMed Central  Google Scholar 

  16. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO et al (2010) 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 62(9):2569–2581

    PubMed  Google Scholar 

  17. Sengul I, Akcay-Yalbuzdag S, Ince B, Goksel-Karatepe A, Kaya T (2015) Comparison of the DAS28-CRP and DAS28-ESR in patients with rheumatoid arthritis. Int J Rheum Dis 18(6):640–645

    PubMed  Google Scholar 

  18. Tonetti MS, Greenwell H, Kornman KS (2018) Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol 89:S159–S172

    PubMed  Google Scholar 

  19. Löe H, Silness J (1963) Periodontal disease in pregnancy I. Prevalence and severity. Acta Odontol Scand 21(6):533–551

    PubMed  Google Scholar 

  20. Boutaga K, van Winkelhoff AJ, Vandenbroucke-Grauls CMJE, Savelkoul PHM (2003) Comparison of real-time PCR and culture for detection of Porphyromonas gingivalis in subgingival plaque samples. J Clin Microbiol 41(11):4950–4954

    PubMed  PubMed Central  Google Scholar 

  21. Bello-Gualtero JM, Lafaurie GI, Hoyos LX, Castillo DM, De-Avila J, Munevar JC et al (2016) Periodontal disease in individuals with a genetic risk of developing arthritis and early rheumatoid arthritis: a cross-sectional study. J Periodontol 87(4):346–356

    PubMed  Google Scholar 

  22. Moses T, Holland PW (2010) A comparison of statistical selection strategies for univariate and bivariate log-linear models. Br J Math Stat Psychol 63(3):557–574

    PubMed  Google Scholar 

  23. Gremese E, Tolusso B, Gigante MR, Ferraccioli G (2014) Obesity as a risk and severity factor in rheumatic diseases (autoimmune chronic inflammatory diseases). Front Immunol 5

  24. Armstrong DJ, McCausland EM, Quinn AD, Wright GD (2006) Obesity and cardiovascular risk factors in rheumatoid arthritis. Rheumatology. 45(6):782–782; author reply 783

    PubMed  Google Scholar 

  25. Carrión M, Frommer KW, Pérez-García S, Müller-Ladner U, Gomariz RP, Neumann E (2019) The adipokine network in rheumatic joint diseases. Int J Mol Sci 20(17):4091

    PubMed Central  Google Scholar 

  26. Liu S, Dong Y, Wang T, Zhao S, Yang K, Chen X, Zheng C (2014) Vaspin inhibited proinflammatory cytokine induced activation of nuclear factor-kappa B and its downstream molecules in human endothelial EA.hy926 cells. Diabetes Res Clin Pract 103(3):482–488

    PubMed  Google Scholar 

  27. Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A (2010) Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch Med Res 41(6):457–463

    PubMed  Google Scholar 

  28. Unriza-Puin S, Bautista-Molano W, Lafaurie GI, Valle-Oñate R, Chalem P, Chila-Moreno L, Bello-Gualtero JM, Romero-Sánchez C (2017) Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives? Clin Rheumatol 36(4):799–806

    PubMed  Google Scholar 

  29. Vidal C, Barnetche T, Morel J, Combe B, Daïen C (2015) Association of body mass index categories with disease activity and radiographic joint damage in rheumatoid arthritis: a systematic review and metaanalysis. J Rheumatol 42(12):2261–2269

    PubMed  Google Scholar 

  30. MacDonald I, Liu S-C, Huang C-C, Kuo S-J, Tsai C-H, Tang C-H (2019) Associations between adipokines in arthritic disease and implications for obesity. Int J Mol Sci 20(6):1505

    Google Scholar 

  31. Lago F, Gómez R, Gómez-Reino JJ, Dieguez C, Gualillo O (2009) Adipokines as novel modulators of lipid metabolism. Trends Biochem Sci 34(10):500–510

    PubMed  Google Scholar 

  32. La Cava A (2017) Leptin in inflammation and autoimmunity. Cytokine. 98:51–58

    PubMed  PubMed Central  Google Scholar 

  33. Tsai S-Y, Chung K-H, Huang S-H, Chen P-H, Lee H-C, Kuo C-J (2014) Persistent inflammation and its relationship to leptin and insulin in phases of bipolar disorder from acute depression to full remission. Bipolar Disord 16(8):800–808

    PubMed  Google Scholar 

  34. Cao H, Lin J, Chen W, Xu G, Sun C (2016) Baseline adiponectin and leptin levels in predicting an increased risk of disease activity in rheumatoid arthritis: a meta-analysis and systematic review. Autoimmunity. 49(8):547–553

    PubMed  Google Scholar 

  35. Olama SM, Senna MK, Elarman M (2012) Synovial/serum leptin ratio in rheumatoid arthritis: the association with activity and erosion. Rheumatol Int 32(3):683–690

    PubMed  Google Scholar 

  36. Tian Y-F, Chang W-C, Loh C-H, Hsieh P-S (2014) Leptin-mediated inflammatory signaling crucially links visceral fat inflammation to obesity-associated β-cell dysfunction. Life Sci 116(1):51–58

    PubMed  Google Scholar 

  37. Zimmermann GS, Bastos MF, Dias Gonçalves TE, Chambrone L, Duarte PM (2013) Local and circulating levels of adipocytokines in obese and normal weight individuals with chronic periodontitis. J Periodontol 84(5):624–633

    PubMed  Google Scholar 

  38. 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

  39. Heredia-P AM, Lafaurie GI, Bautista-Molano W, Trujillo TG, Chalem-Choueka P, Bello-Gualtero JM, Pacheco-Tena C, Chila-Moreno L, Romero-Sánchez C (2019) Predictive factors related to the progression of periodontal disease in patients with early rheumatoid arthritis: a cohort study. BMC Oral Health. 19(1):240

    PubMed  PubMed Central  Google Scholar 

  40. Han JY, Reynolds MA (2012) Effect of anti-rheumatic agents on periodontal parameters and biomarkers of inflammation: a systematic review and meta-analysis. J Periodontal Implant Sci 42(1):3–12

    PubMed  PubMed Central  Google Scholar 

  41. Holzhausen M, Rossa C, Marcantonio E, Nassar PO, Spolidório DMP, Spolidório LC (2002) Effect of selective cyclooxygenase-2 inhibition on the development of ligature-induced periodontitis in rats. J Periodontol 73(9):1030–1036

    PubMed  Google Scholar 

  42. Korpela M, Laasonen L, Hannonen P, Kautiainen H, Leirisalo-Repo M, Hakala M, Paimela L, Blåfield H, Puolakka K, Möttönen T, FIN-RACo Trial Group (2004) Retardation of joint damage in patients with early rheumatoid arthritis by initial aggressive treatment with disease-modifying antirheumatic drugs: five-year experience from the FIN-RACo study. Arthritis Rheum 50(7):2072–2081

    PubMed  Google Scholar 

  43. Jung G-U, Han J-Y, Hwang K-G, Park C-J, Stathopoulou PG, Fiorellini JP (2018) Effects of conventional synthetic disease-modifying antirheumatic drugs on response to periodontal treatment in patients with rheumatoid arthritis. Biomed Res Int 2018:1–7

    Google Scholar 

  44. Kordtabar S, Aghaie M, Fakhari E, Vakili MA (2019) Periodontal condition in patients with rheumatoid arthritis: effect of anti-rheumatic drugs. J Dent (Shiraz, Iran) 20(3):190–194

    Google Scholar 

  45. Gerhard KM, Endresen GH (2001) Folate supplementation during methotrexate treatment of patients with rheumatoid arthritis: an update and proposals for guidelines. Scand J Rheumatol 30(3):129–134

    Google Scholar 

  46. Deeming GMJ, Collingwood J, Pemberton MN (2005) Methotrexate and oral ulceration. Br Dent J 198(2):83–85

    PubMed  Google Scholar 

  47. Bae S-C, Lee YH (2018) Association between anti-Porphyromonas gingivalis antibody, anti-citrullinated protein antibodies, and rheumatoid arthritis. Z Rheumatol 77(6):522–532

    PubMed  Google Scholar 

  48. Targońska-Stępniak B, Majdan M, Dryglewska M (2008) Leptin serum levels in rheumatoid arthritis patients: relation to disease duration and activity. Rheumatol Int 28(6):585–591

    PubMed  Google Scholar 

  49. Maijer KI, Neumann E, Müller-ladner U, Drop DACAD, Ramwadhdoebe TH, Choi IYK, et al. (2015) Serum vaspin levels are associated with the development of clinically manifest arthritis in autoantibody-positive individuals. Frey O, editor. PLoS One;10(12):e0144932

  50. Senolt L, Polanska M, Filkova M, Cerezo LA, Pavelka K, Gay S, Haluzik M, Vencovsky J (2010) Vaspin and omentin: new adipokines differentially regulated at the site of inflammation in rheumatoid arthritis. Ann Rheum Dis 69(7):1410–1411

    PubMed  Google Scholar 

  51. Mattioli B, Straface E, Giovanna M, Giordani L, Viora M, Mattioli B et al (2005) Leptin promotes differentiation and survival of human dendritic cells and licenses them for Th1 priming. J Immun 174(11):6820–6828

    PubMed  Google Scholar 

  52. Faggioni R, Fantuzzi G, Fuller J, Dinarello CA, Feingold KR, Grunfeld C (1998) IL-1β mediates leptin induction during inflammation. Am J Physiol Integr Comp Physiol 274(1):R204–R208

    Google Scholar 

  53. Sarraf P, Frederich RC, Turner EM, Ma G, Jaskowiak NT, Rivet DJ et al (1997) Multiple cytokines and acute inflammation raise mouse leptin levels: potential role in inflammatory anorexia. J Exp Med 185(1):171–176

    PubMed  PubMed Central  Google Scholar 

  54. Gonçalves TED, Zimmermann GS, Figueiredo LC, Souza M d C, da Cruz DF, Bastos MF et al (2015) Local and serum levels of adipokines in patients with obesity after periodontal therapy: one-year follow-up. J Clin Periodontol 42(5):431–439

    PubMed  Google Scholar 

  55. de Molon RS, Rossa C Jr, Thurlings RM, Cirelli JA, Koenders MI (2019) Linkage of periodontitis and rheumatoid arthritis: current evidence and potential biological interactions. Int J Mol Sci 20(18):4541

    Google Scholar 

  56. Romero-Sanchez C, Rodríguez C, Santos-Moreno P, Mesa AM, Lafaurie GI, Giraldo-Q S, de-Avila J, Castillo DM, Duran M, Chalem PC, Bello Gualtero JM, Valle-Oñate R (2017) Is the treatment with biological or non-biological DMARDS a modifier of periodontal condition in patients with rheumatoid arthritis? Curr Rheumatol Rev 13(2):139–151

    PubMed  Google Scholar 

  57. Tang Q, Fu H, Qin B, Hu Z, Liu Y, Liang Y, Zhou L, Yang Z, Zhong R (2017) A possible link between rheumatoid arthritis and periodontitis: a systematic review and meta-analysis. Int J Periodontics Restorative Dent 37(1):79–86

    PubMed  Google Scholar 

  58. Mikuls TR, Payne JB, Yu F, Thiele GM, Reynolds RJ, Cannon GW, Markt J, McGowan D, Kerr GS, Redman RS, Reimold A, Griffiths G, Beatty M, Gonzalez SM, Bergman DA, Hamilton BC III, Erickson AR, Sokolove J, Robinson WH, Walker C, Chandad F, O'Dell JR (2014) Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. Arthritis Rheumatol 66(5):1090–1100

    PubMed  PubMed Central  Google Scholar 

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Acknowledgments

Thanks are given to doctors Sebastian Giraldo and Andrea Chaparro for their clinical support and Alejandro Ramos for editing the manuscript.

Funding

This study was supported by the Administrative Department of Science, Technology, and Innovation-COLCIENCIAS (Grant No. 130865740792–2014), Hospital Militar Grant 2016–099, Fundación Instituto de Reumatología Fernando Chalem and Universidad El Bosque.

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Correspondence to Consuelo Romero-Sánchez.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The study was approved by the Institutional Ethics Committee, code HMC 2016–041 and HMC 2016–099.

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Rodríguez, J., Lafaurie, G.I., Bautista-Molano, W. et al. Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: a cross-sectional study. Clin Oral Invest 25, 1685–1695 (2021). https://doi.org/10.1007/s00784-020-03469-0

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