Periodontal Inflammation Effect Salivary and Serum C-Reactive Protein and Fetuin-A Levels?

Öz

Objective: Periodontal disease triggers the immune response by affecting the host defence system. Positive and negative acute phase reactants, mostly secreted by liver, are released as a result of inflammation. Periodontal inflamed surface area (PISA) has recently been used to measure the inflammatory load caused by periodontitis. The purpose of this study is to examine the effects of PISA on the levels of positive, negative acute phase reactants C-reactive protein (CRP) and fetuin-A in saliva and serum.

Material-Method: Forty-seven individuals were included in the study and divided into 3 groups according to their periodontal status as periodontal healthy (n=15), gingivitis (n=15), or periodontitis (n=17). Sociodemographics were recorded through a questionnaire, periodontal indices were taken, and saliva and serum samples were collected from patients. PISA was calculated using periodontal probing depth, clinical attachment level, and percentage of bleeding on probing. CRP and fetuin-A levels in saliva and serum samples were analysed by ELISA.

Results: Periodontal parameters and PISA were higher in periodontitis group than healthy and gingivitis group. When compared to healthy group, salivary CRP was higher and salivary and serum fetuin-A was lower in periodontitis group. Serum fetuin-A was lower and salivary CRP was higher in periodontitis group compared to gingivitis group. As a result of the adjusted multivariate linear regression analysis, it was determined that PISA was negatively correlated with salivary and serum fetuin-A, and positively correlated with serum CRP.

Conclusions: Fetuin-A and CRP levels were suggested to be used as a biomarker in periodontal disease pathogenesis.

Anahtar Kelimeler

• Alpha-2-HS-Glycoprotein
• C-Reactive Protein
• Fetuins
• Periodontitis

Periodontal İnflamasyon Salya, Serum C-Reaktif Protein ve Fetuin-A Düzeylerini Etkiler mi?

Öz

Amaç: Periodontal hastalık konak savunma sistemini etkileyerek immün yanıtı harekete geçirmektedir. İnflamasyon sonucunda çoğunluğu karaciğer tarafından salgılanan pozitif ve negatif akut faz reaktanları açığa çıkmaktadır. Periodontitisin oluşturduğu inflamatuvar yükü ölçmek için periodontal inflame yüzey alanı (PİYA) son zamanlarda kullanılmaya başlanmıştır. Bu çalışmanın amacı PİYA’nın salya ve serumda pozitif, negatif akut faz reaktanları olan C-reaktif protein (CRP) ve fetuin-A seviyelerine etkilerini incelemektir.
Materyal-Metot: Çalışmaya 47 birey dahil edildi ve periodontal durumlarına göre periodontal olarak sağlıklı (n=15), gingivitis (n=15) ve periodontitis (n=17) olmak üzere 3 gruba ayrıldı. Hastaların sosyodemografik verileri anket aracılığıyla kaydedildi, periodontal kayıtları alındı, hastalardan salya ve serum örnekleri toplandı. PİYA, periodontal cep derinliği, klinik ataşman seviyesi ve sondalamada kanama yüzdesi kullanılarak hesaplandı. Salya ve serum örneklerinde CRP ve fetuin-A seviyeleri ELISA ile analiz edildi.
Bulgular: Periodontal parametreler ve PİYA periodontitisli grupta sağlıklı ve gingivitisli gruba göre daha yüksekti. Sağlıklı grupla kıyaslandığında periodontitis grubunda salya CRP daha yüksek, salya ve serum fetuin-A ise daha düşüktü. Periodontitis grubunda gingivitisli gruba kıyasla serum fetuin-A daha düşük, salya CRP daha yüksekti. Uyumlandırılmış çok değişkenli lineer regresyon analizi sonucunda PİYA ile salya ve serum fetuin-A’nın negatif, serum CRP’nin ise pozitif ilişkili olduğu belirlendi.
Sonuç: Fetuin-A ve CRP seviyelerinin periodontal hastalık patogenezinde biyobelirteç olarak kullanılabileceği öngörülmektedir. 

Anahtar Kelimeler

• Alfa-2-HS-Glikoprotein
• C-Reaktif Protein
• Fetuinler
• Periodontitis

Kaynakça

1. [1] Page RC. The role of inflammatory mediators in the pathogenesis of periodontal disease. J Periodontal Res. 1991;26(3 Pt 2):230-42.
2. [2] Baumann H, Gauldie J. The acute phase response. Immunol Today. 1994;15(2):74-80.
3. [3] Ebersole JL, Cappelli D. Acute-phase reactants in infections and inflammatory diseases. Periodontol 2000. 2000;23:19-49.
4. [4] Nunes BK, Lacerda RA, Jardim JM. [Systematic review and meta-analysis of the predictive value of C-reactive protein in postoperative infections]. Rev Esc Enferm USP. 2011;45(6):1488-94.
5. [5] Gomes-Filho IS, Freitas Coelho JM, da Cruz SS, Passos JS, Teixeira de Freitas CO, Aragao Farias NS, et al. Chronic periodontitis and C-reactive protein levels. J Periodontol. 2011;82(7):969-78.
6. [6] Schoffer C, Oliveira LM, Santi SS, Antoniazzi RP, Zanatta FB. C-reactive protein levels are associated with periodontitis and periodontal inflamed surface area in adults with endstage renal disease. J Periodontol. 2021;92(6):793-802.
7. [7] Al-Zahrani MS, Alghamdi HS. Effect of periodontal treatment on serum C-reactive protein level in obese and normal-weight women affected with chronic periodontitis. Saudi Med J. 2012;33(3):309-14.
8. [8] Paraskevas S, Huizinga JD, Loos BG. A systematic review and meta-analyses on Creactive protein in relation to periodontitis. J Clin Periodontol. 2008;35(4):277-90.

9. [9] Bansal T, Pandey A, D D, Asthana AK. C-Reactive Protein (CRP) and its Association with Periodontal Disease: A Brief Review. J Clin Diagn Res. 2014;8(7):ZE21-4.
10. [10] Denecke B, Graber S, Schafer C, Heiss A, Woltje M, Jahnen-Dechent W. Tissue distribution and activity testing suggest a similar but not identical function of fetuin-B and fetuin-A. Biochem J. 2003;376(Pt 1):135-45.
11. [11] Mori K, Emoto M, Inaba M. Fetuin-A: a multifunctional protein. Recent Pat Endocr Metab Immune Drug Discov. 2011;5(2):124-46.
12. [12] Furugen R, Kawasaki K, Kitamura M, Maeda T, Saito T, Hayashida H. Association of low fetuin-A levels with periodontitis in community-dwelling adults. J Oral Sci. 2020;62(1):67-9.
13. [13] Nair S, Nisha KJ. Evaluation of the effect of scaling and root planing on salivary and serum fetuin-A levels in patients with stages II and III periodontitis. J Periodontol. 2021.
14. [14] Turer CC, Balli U, Guven B. Fetuin-A, serum amyloid A and tumor necrosis factor alpha levels in periodontal health and disease. Oral Dis. 2017;23(3):379-86.
15. [15] Ersin Kalkan R, Ongoz Dede F, Gokmenoglu C, Kara C. Salivary fetuin-A, S100A12, and high-sensitivity C-reactive protein levels in periodontal diseases. Oral Dis. 2018;24(8):1554-61.
16. [16] Nesse W, Abbas F, van der Ploeg I, Spijkervet FK, Dijkstra PU, Vissink A. Periodontal inflamed surface area: quantifying inflammatory burden. J Clin Periodontol. 2008;35(8):668-73.
17. [17] Susanto H, Nesse W, Dijkstra PU, Hoedemaker E, van Reenen YH, Agustina D, et al. Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c: a study in Indonesia. Clin Oral Investig. 2012;16(4):1237-42.
18. [18] Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89 Suppl 1:S173-S82.
19. [19] Chapple ILC, Mealey BL, Van Dyke TE, Bartold PM, Dommisch H, Eickholz P, et al. Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89 Suppl 1:S74-S84.
20. [20] Silness J, Löe H. Periodontal disease in pregnancy II. Correlation between oral hygiene and periodontal condition. Acta odontologica scandinavica. 1964;22(1):121-35.
21. [21] Löe H, Silness J. Periodontal disease in pregnancy I. Prevalence and severity. Acta odontologica scandinavica. 1963;21(6):533-51.
22. [22] Navazesh M. Methods for collecting saliva. Annals of the New York Academy of Sciences. 1993;694(1):72-7.
23. [23] Wang H, Sama AE. Anti-inflammatory role of fetuin-A in injury and infection. Curr Mol Med. 2012;12(5):625-33.
24. [24] Archana V, Ambili R, Nisha KJ, Seba A, Preeja C. Acute-phase reactants in periodontal disease: current concepts and future implications. J Investig Clin Dent. 2015;6(2):108-17.
25. [25] Fatima T, Khurshid Z, Rehman A, Imran E, Srivastava KC, Shrivastava D. Gingival Crevicular Fluid (GCF): A Diagnostic Tool for the Detection of Periodontal Health and Diseases. Molecules. 2021;26(5).
26. [26] Buzalaf MAR, Ortiz AC, Carvalho TS, Fideles SOM, Araujo TT, Moraes SM, et al. Saliva as a diagnostic tool for dental caries, periodontal disease and cancer: is there a need for more biomarkers? Expert Rev Mol Diagn. 2020;20(5):543-55.
27. [27] Nomura Y, Tamaki Y, Tanaka T, Arakawa H, Tsurumoto A, Kirimura K, et al. Screening of periodontitis with salivary enzyme tests. J Oral Sci. 2006;48(4):177-83.
28. [28] Al-Zahrani MS, Bissada NF, Borawskit EA. Obesity and periodontal disease in young, middle-aged, and older adults. J Periodontol. 2003;74(5):610-5.
29. [29] Leira Y, Rodriguez-Yanez M, Arias S, Lopez-Dequidt I, Campos F, Sobrino T, et al. Periodontitis is associated with systemic inflammation and vascular endothelial dysfunction in patients with lacunar infarct. J Periodontol. 2019;90(5):465-74.
30. [30] Nesse W, Linde A, Abbas F, Spijkervet FK, Dijkstra PU, de Brabander EC, et al. Doseresponse relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol. 2009;36(4):295-300.
31. [31] Panichi V, Migliori M, De Pietro S, Taccola D, Andreini B, Metelli MR, et al. The link of biocompatibility to cytokine production. Kidney International. 2000;58:S96-S103.
32. [32] Schulz S, Ludike H, Lierath M, Schlitt A, Werdan K, Hofmann B, et al. C-reactive protein levels and genetic variants of CRP as prognostic markers for combined cardiovascular endpoint (cardiovascular death, death from stroke, myocardial infarction, and stroke/TIA). Cytokine. 2016;88:71-6.
33. [33] Miki K, Kitamura M, Hatta K, Kamide K, Gondo Y, Yamashita M, et al. Periodontal inflamed surface area is associated with hs-CRP in septuagenarian Japanese adults in crosssectional findings from the SONIC study. Sci Rep. 2021;11(1):14436.
34. [34] Szweras M, Liu D, Partridge EA, Pawling J, Sukhu B, Clokie C, et al. alpha 2-HS glycoprotein/fetuin, a transforming growth factor-beta/bone morphogenetic protein antagonist, regulates postnatal bone growth and remodeling. J Biol Chem. 2002;277(22):19991-7.
35. [35] Jablonski H, Polan C, Wedemeyer C, Hilken G, Schlepper R, Bachmann HS, et al. A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis. Bone. 2017;105:262-8.