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Current Rheumatology Reviews

Editor-in-Chief

ISSN (Print): 1573-3971
ISSN (Online): 1875-6360

Research Article

Adipokine Profile on Joint and Periodontal Conditions in First-degree Relatives of Patients with Rheumatoid Arthritis

Author(s): Alejandro Ramos-Casallas, Juliette De Avila, Andrea Chaparro‐Sanabria, Philippe Chalem Choueka, Juan Manuel Bello-Gualtero, Lorena Chila-Moreno, César Pacheco-Tena, Wilson Bautista-Molano and Consuelo Romero-Sánchez*

Volume 19, Issue 3, 2023

Published on: 23 November, 2022

Page: [321 - 329] Pages: 9

DOI: 10.2174/1573397118666220920104900

Price: $65

Abstract

Background: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by joint inflammation and destruction.

Objective: Establish the association between Porphyromonas gingivalis (P. gingivalis) infection, body mass index (BMI), joint involvement, and serum adipokines in first-degree relatives (FDR) of patients with rheumatoid arthritis (RA).

Methods: The cross-sectional study evaluated 124 FDR and 124 healthy controls (HC). The clinical examination included joint and radiographic evaluation and calculation of BMI. Serum adipokine levels were measured (leptin, vaspin, adiponectin, resistin, and adipsin), as were the erythrocyte sedimentation rate, C-reactive protein, and anti-citrullinated protein antibodies. Investigations were performed to detect P. gingivalis, and anti-P. gingivalis antibodies. Statistical analyses were performed to confirm associations.

Results: Leptin levels in FDR were associated with BMI >25 (OR, 2.64; 95%CI, 1.17-5.97; P=0.019), radiographic damage (Simple Erosion Narrowing Score [SENS])/hands, total SENS, and joint space narrowing in feet (P=0.037, 0.026, 0.020, respectively). FDR had more tender joints (P=0.018); this finding was associated with high levels of leptin and resistin and low levels of adipsin (P=0.040, 0.040, and 0.019, respectively).

The presence of P. gingivalis was related to FDR, low levels of adipsin, resistin, adiponectin, and a trend toward higher levels of leptin (P=0.002, 0.001, 0.003, and 0.060, respectively), whereas anti-P. gingivalis antibodies were related to low levels of adipsin (P=0.001).

Conclusion: In FDR, serum adipokine levels were associated with overweight and the presence of P. gingivalis. Adipokine levels were also associated with joint involvement. Hence, adipokines may be involved in the pathogenesis of RA in FDR and warrant further investigation.

Keywords: Adipokines, joints, body mass index, Porphyromonas gingivalis, relatives, rheumatoid arthritis

Graphical Abstract

[1]
Firestein GS. Evolving concepts of rheumatoid arthritis. Nature 2003; 423(6937): 356-61.
[http://dx.doi.org/10.1038/nature01661] [PMID: 12748655]
[2]
Londoño J, Peláez Ballestas I, Cuervo F, et al. Prevalencia de la enfermedad reumática en Colombia, según estrategia COPCORD-Asociación Colombiana de Reumatología. Estudio de prevalencia de enfermedad reumática en población colombiana mayor de 18 años. Revista Colombiana de Reumatología 2018; 25(4): 245-56.
[http://dx.doi.org/10.1016/j.rcreu.2018.08.003]
[3]
Bello-Gualtero JM, Lafaurie GI, Hoyos LX, et al. Periodontal disease in individuals with a genetic risk of developing arthritis and early rheumatoid arthritis: A cross-sectional study. J Periodontol 2016; 87(4): 346-56.
[http://dx.doi.org/10.1902/jop.2015.150455] [PMID: 26609697]
[4]
Unriza-Puin S, Bautista-Molano W, Lafaurie GI, et al. Are obesity, ACPAs and periodontitis conditions that influence the risk of developing rheumatoid arthritis in first-degree relatives? Clin Rheumatol 2017; 36(4): 799-806.
[http://dx.doi.org/10.1007/s10067-016-3519-z] [PMID: 28028684]
[5]
Gerlag DM, Raza K, van Baarsen LGM, et al. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: Report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann Rheum Dis 2012; 71(5): 638-41.
[http://dx.doi.org/10.1136/annrheumdis-2011-200990] [PMID: 22387728]
[6]
MacGregor AJ, Snieder H, Rigby AS, et al. Characterizing the quantitative genetic contribution to rheumatoid arthritis using data from twins. Arthritis Rheum 2000; 43(1): 30-7.
[http://dx.doi.org/10.1002/1529-0131(200001)43:1<30::AID-ANR5>3.0.CO;2-B] [PMID: 10643697]
[7]
Lundberg K, Wegner N, Yucel-Lindberg T, Venables PJ. Periodontitis in RA-the citrullinated enolase connection. Nat Rev Rheumatol 2010; 6(12): 727-30.
[http://dx.doi.org/10.1038/nrrheum.2010.139] [PMID: 20820197]
[8]
Nikiphorou E, Norton S, Young A, et al. The association of obesity with disease activity, functional ability and quality of life in early rheumatoid arthritis: data from the early rheumatoid arthritis study/early rheumatoid arthritis network UK prospective cohorts. Rheumatology 2018; 57(7): 1194-202.
[http://dx.doi.org/10.1093/rheumatology/key066] [PMID: 29590474]
[9]
Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokines in inflammation and metabolic disease. Nat Rev Immunol 2011; 11(2): 85-97.
[http://dx.doi.org/10.1038/nri2921] [PMID: 21252989]
[10]
Krysiak R, Handzlik-Orlik G, Okopien B. The role of adipokines in connective tissue diseases. Eur J Nutr 2012; 51(5): 513-28.
[http://dx.doi.org/10.1007/s00394-012-0370-0] [PMID: 22584415]
[11]
Liu S, Dong Y, Wang T, et al. 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 2014; 103(3): 482-8.
[http://dx.doi.org/10.1016/j.diabres.2013.12.002] [PMID: 24418398]
[12]
Zhao Y, Chen C. Adipsin as adipokineAdipokines. United Kingdom: CRC Press 2017; pp. 20-7.
[13]
Fantuzzi G. Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005; 115(5): 911-9.
[http://dx.doi.org/10.1016/j.jaci.2005.02.023] [PMID: 15867843]
[14]
Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H, Sugita N, Yoshie H. The effect of periodontal treatment on serum leptin, interleukin-6, and C-reactive protein. J Periodontol 2010; 81(8): 1118-23.
[http://dx.doi.org/10.1902/jop.2010.090741] [PMID: 20370420]
[15]
Zimmermann GS, Bastos MF, Dias GTE, Chambrone L, Duarte PM. Local and circulating levels of adipocytokines in obese and normal weight individuals with chronic periodontitis. J Periodontol 2013; 84(5): 624-33.
[http://dx.doi.org/10.1902/jop.2012.120254] [PMID: 22839694]
[16]
Nokhbehsaim M, Keser S, Nogueira AVB, et al. Beneficial effects of adiponectin on periodontal ligament cells under normal and regenerative conditions. J Diabetes Res 2014; 2014: 1-11.
[http://dx.doi.org/10.1155/2014/796565] [PMID: 25121107]
[17]
Nokhbehsaim M, Keser S, Nogueira AVB, et al. Leptin effects on the regenerative capacity of human periodontal cells. Int J Endocrinol 2014; 2014: 1-13.
[http://dx.doi.org/10.1155/2014/180304] [PMID: 25136363]
[18]
Chaparro‐Sanabria JA, Bautista‐Molano W, Bello‐Gualtero JM, et al. 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. Int J Rheum Dis 2019; 1-14.
[http://dx.doi.org/10.1111/1756-185X.13724] [PMID: 31659869]
[19]
Klein-Wieringa IR, van der Linden MPM, Knevel R, et al. Baseline serum adipokine levels predict radiographic progression in early rheumatoid arthritis. Arthritis Rheum 2011; 63(9): 2567-74.
[http://dx.doi.org/10.1002/art.30449] [PMID: 21567382]
[20]
Maijer KI, Neumann E, Müller-Ladner U, et al. Serum vaspin levels are associated with the development of clinically manifest arthritis in autoantibody-positive individuals. PLoS One 2015; 10(12): e0144932.
[http://dx.doi.org/10.1371/journal.pone.0144932] [PMID: 26670468]
[21]
Rodríguez J, Lafaurie GI, Bautista-Molano W, Chila-Moreno L, Bello-Gualtero JM, Romero-Sánchez C. Adipokines and periodontal markers as risk indicators of early rheumatoid arthritis: A cross-sectional study. Clin Oral Investig 2021; 25(4): 1685-95.
[http://dx.doi.org/10.1007/s00784-020-03469-0] [PMID: 32740810]
[22]
National Human Genome Research Institute. First degree relative. Available from: https://www.genome.gov/genetics-glossary/First-Degree-Relative (Accessed on: July 21, 2022).
[23]
Dias EM, Lukas C, Landewé R, Fatenejad S, van der Heijde D. Reliability and sensitivity to change of the Simple Erosion Narrowing Score compared with the Sharp-van der Heijde method for scoring radiographs in rheumatoid arthritis. Ann Rheum Dis 2007; 67(3): 375-9.
[http://dx.doi.org/10.1136/ard.2007.072785] [PMID: 17644537]
[24]
Winkler TW, Justice AE, Graff M, et al. The influence of age and sex on genetic associations with adult body size and shape: A large-scale genome-wide interaction study. PLoS Genet 2015; 11(10): e1005378.
[http://dx.doi.org/10.1371/journal.pgen.1005378] [PMID: 26426971]
[25]
Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA 2006; 295(13): 1549-55.
[http://dx.doi.org/10.1001/jama.295.13.1549] [PMID: 16595758]
[26]
Filozof C, Gonzalez C, Sereday M, Mazza C, Braguinsky J. Obesity prevalence and trends in Latin-American countries. Obes Rev 2001; 2(2): 99-106.
[http://dx.doi.org/10.1046/j.1467-789x.2001.00029.x] [PMID: 12119667]
[27]
Ruderman A, Pérez LO, Adhikari K, et al. Obesity, genomic ancestry, and socioeconomic variables in Latin American mestizos. Am J Hum Biol 2019; 31(5): e23278.
[http://dx.doi.org/10.1002/ajhb.23278] [PMID: 31237064]
[28]
Kasper NM, Herrán OF, Villamor E. Obesity prevalence in Colombian adults is increasing fastest in lower socio-economic status groups and urban residents: Results from two nationally representative surveys. Public Health Nutr 2014; 17(11): 2398-406.
[http://dx.doi.org/10.1017/S1368980013003418] [PMID: 24476690]
[29]
Kanter R, Caballero B. Global gender disparities in obesity: A review. Adv Nutr 2012; 3(4): 491-8.
[http://dx.doi.org/10.3945/an.112.002063] [PMID: 22797984]
[30]
Sparks JA, Chen CY, Hiraki LT, Malspeis S, Costenbader KH, Karlson EW. Contributions of familial rheumatoid arthritis or lupus and environmental factors to risk of rheumatoid arthritis in women: A prospective cohort study. Arthritis Care Res 2014; 66(10): 1438-46.
[http://dx.doi.org/10.1002/acr.22366] [PMID: 25103278]
[31]
Sparks JA, Iversen MD, Yu Z, et al. Disclosure of personalized rheumatoid arthritis risk using genetics, biomarkers, and lifestyle factors to motivate health behavior improvements: A randomized controlled trial. Arthritis Care Res 2018; 70(6): 823-33.
[http://dx.doi.org/10.1002/acr.23411] [PMID: 29024454]
[32]
Ministerio de Salud y Protección Social. IV Estudio Nacional de Salud Bucal - ENSAB IV. 2014.
[33]
Mikuls TR, Thiele GM, Deane KD, et al. Porphyromonas gingivalis and disease-related autoantibodies in individuals at increased risk of rheumatoid arthritis. Arthritis Rheum 2012; 64(11): 3522-30.
[http://dx.doi.org/10.1002/art.34595] [PMID: 22736291]
[34]
Johansson L, Sherina N, Kharlamova N, et al. Concentration of antibodies against Porphyromonas gingivalis is increased before the onset of symptoms of rheumatoid arthritis. Arthritis Res Ther 2016; 18(1): 201.
[http://dx.doi.org/10.1186/s13075-016-1100-4] [PMID: 27605245]
[35]
Le Sage F, Meilhac O, Gonthier MP. Porphyromonas gingivalis lipopolysaccharide induces pro-inflammatory adipokine secretion and oxidative stress by regulating Toll-like receptor-mediated signaling pathways and redox enzymes in adipocytes. Mol Cell Endocrinol 2017; 446: 102-10.
[http://dx.doi.org/10.1016/j.mce.2017.02.022] [PMID: 28216438]
[36]
Schenkein HA. Complement factor D̄-like activity of Porphyromonas gingivalis W83. Oral Microbiol Immunol 1991; 6(4): 216-20.
[http://dx.doi.org/10.1111/j.1399-302X.1991.tb00480.x] [PMID: 1667434]
[37]
Bokarewa M, Nagaev I, Dahlberg L, Smith U, Tarkowski A. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005; 174(9): 5789-95.
[http://dx.doi.org/10.4049/jimmunol.174.9.5789] [PMID: 15843582]
[38]
White RT, Damm D, Hancock N, et al. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem 1992; 267(13): 9210-3.
[http://dx.doi.org/10.1016/S0021-9258(19)50409-4] [PMID: 1374388]
[39]
Akram Z, Rahim ZHA, Taiyeb-Ali TB, et al. Resistin as potential biomarker for chronic periodontitis: A systematic review and meta-analysis. Arch Oral Biol 2017; 73: 311-20.
[http://dx.doi.org/10.1016/j.archoralbio.2016.08.016] [PMID: 27567495]
[40]
Del Prete A, Salvi V, Sozzani S. Adipokines as potential biomarkers in rheumatoid arthritis. Mediators Inflamm 2014; 2014: 1-11.
[http://dx.doi.org/10.1155/2014/425068] [PMID: 24799765]
[41]
Li Y, Zou W, Brestoff JR, et al. Fat-Produced Adipsin Regulates Inflammatory Arthritis. Cell Rep 2019; 27(10): 2809-2816.e3.
[http://dx.doi.org/10.1016/j.celrep.2019.05.032] [PMID: 31167128]

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