Complement components C3b and C4b as potential reliable site-specific diagnostic biomarkers for periodontitis.
complement C3b
complement C4b
complement system proteins
diagnosis
periodontitis
site-specific
Journal
Journal of periodontal research
ISSN: 1600-0765
Titre abrégé: J Periodontal Res
Pays: United States
ID NLM: 0055107
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
24
06
2023
received:
30
03
2023
accepted:
08
07
2023
medline:
11
9
2023
pubmed:
18
7
2023
entrez:
18
7
2023
Statut:
ppublish
Résumé
This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis. A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce. The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed. The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001). Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.
Sections du résumé
OBJECTIVE
OBJECTIVE
This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis.
BACKGROUND
BACKGROUND
A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce.
METHODS
METHODS
The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed.
RESULTS
RESULTS
The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001).
CONCLUSIONS
CONCLUSIONS
Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1020-1030Subventions
Organisme : Tri-Service General Hospital
ID : TSGH-D-110059
Organisme : Tri-Service General Hospital
ID : TSGH-E-110208
Organisme : Tri-Service General Hospital
ID : TSGH-E-111199
Organisme : Ministry of National Defense
ID : MND-MAB-110-127
Organisme : Ministry of National Defense
ID : MND-MAB-110-124
Organisme : Small Business Innovation Research in Taiwan
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Schenkein HA, Papapanou PN, Genco R, Sanz M. Mechanisms underlying the association between periodontitis and atherosclerotic disease. Periodontol. 2020;83(1):90-106.
Kapila YL. Oral health's inextricable connection to systemic health: special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions. Periodontol. 2021;87(1):11-16.
Van Dyke TE, Bartold PM, Reynolds EC. The nexus between periodontal inflammation and dysbiosis. Front Immunol. 2020;11:511.
Balta MG, Papathanasiou E, Blix IJ, Van Dyke TE. Host modulation and treatment of periodontal disease. J Dent Res. 2021;100(8):798-809.
Loos BG, Van Dyke TE. The role of inflammation and genetics in periodontal disease. Periodontol. 2020;83(1):26-39.
Ghallab NA. Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: review of the current evidence. Arch Oral Biol. 2018;87:115-124.
Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: case definition and diagnostic considerations. J Clin Periodontol. 2018;45(Suppl 20):S44-S67.
Taba M Jr, Kinney J, Kim AS, Giannobile WV. Diagnostic biomarkers for oral and periodontal diseases. Dent Clin N Am. 2005;49(3):551-571, vi.
Kajikawa T, Mastellos DC, Hasturk H, et al. C3-targeted host-modulation approaches to oral inflammatory conditions. Semin Immunol. 2022;59:101608.
Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3-11.
Reis ES, Mastellos DC, Hajishengallis G, Lambris JD. New insights into the immune functions of complement. Nat Rev Immunol. 2019;19(8):503-516.
Hajishengallis G, Kajikawa T, Hajishengallis E, et al. Complement-dependent mechanisms and interventions in periodontal disease. Front Immunol. 2019;10:406.
Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-797.
Lewis LA, Ram S, Prasad A, et al. Defining targets for complement components C4b and C3b on the pathogenic neisseriae. Infect Immun. 2008;76(1):339-350.
Sharma M, Vignesh P, Tiewsoh K, Rawat A. Revisiting the complement system in systemic lupus erythematosus. Expert Rev Clin Immunol. 2020;16(4):397-408.
Jia H, Li T, Sun J, et al. A novel bispecific fusion protein targeting C3b/C4b and VEGF in patients with nAMD: a randomized, open-label, phase 1b study. Am J Ophthalmol. 2022;248:8-15.
Huang RY, Tseng FY, You JJ, et al. Targeting therapeutic agent against C3b/C4b, SB002, on the inflammation-induced bone loss in experimental periodontitis. J Clin Periodontol. 2023;50(5):657-670.
Hajishengallis G, Krauss JL, Jotwani R, Lambris JD. Differential capacity for complement receptor-mediated immune evasion by Porphyromonas gingivalis depending on the type of innate leukocyte. Mol Oral Microbiol. 2017;32(2):154-165.
Wang M, Krauss JL, Domon H, et al. Microbial hijacking of complement-toll-like receptor crosstalk. Sci Signal. 2010;3(109):ra11.
Jusko M, Potempa J, Mizgalska D, et al. A metalloproteinase Mirolysin of Tannerella forsythia inhibits all pathways of the complement system. J Immunol. 2015;195(5):2231-2240.
Potempa M, Potempa J, Kantyka T, et al. Interpain a, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3. PLoS Pathog. 2009;5(2):e1000316.
Damgaard C, Holmstrup P, Van Dyke TE, Nielsen CH. The complement system and its role in the pathogenesis of periodontitis: current concepts. J Periodontal Res. 2015;50(3):283-293.
Patters MR, Niekrash CE, Lang NP. Assessment of complement cleavage in gingival fluid during experimental gingivitis in man. J Clin Periodontol. 1989;16(1):33-37.
Attstrom R, Laurel AB, Lahsson U, Sjoholm A. Complement factors in gingival crevice material from healthy and inflamed gingiva in humans. J Periodontal Res. 1975;10(1):19-27.
Courts FJ, Boackle RJ, Fudenberg HH, Silverman MS. Detection of functional complement components in gingival crevicular fluid from humans with periodontal diseases. J Dent Res. 1977;56(3):327-331.
Schenkein HA, Genco RJ. Gingival fluid and serum in periodontal diseases. II. Evidence for cleavage of complement components C3, C3 proactivator (factor B) and C4 in gingival fluid. J Periodontol. 1977;48(12):778-784.
Damgaard C, Massarenti L, Danielsen AK, et al. Complement component 3 (C3) and its activation split-products in saliva associate with periodontitis. J Periodontol. 2022;93:1294-1301.
Hasturk H, Hajishengallis G, Forsyth Institute Center for Clinical and Translational Research staff, Lambris JD, Mastellos DC, Yancopoulou D. Phase IIa clinical trial of complement C3 inhibitor AMY-101 in adults with periodontal inflammation. J Clin Invest. 2021;131(23):e152973.
Niekrash CE, Patters MR. Simultaneous assessment of complement components C3, C4, and B and their cleavage products in human gingival fluid. II. Longitudinal changes during periodontal therapy. J Periodontal Res. 1985;20(3):268-275.
Bhalla SP, Shaju AM, Figueredo C, Miranda LA. Increased levels of C5a in gingival crevicular fluid and saliva of patients with periodontal disease. Pathogens. 2022;11(9):983.
Grande MA, Belstrom D, Damgaard C, et al. Complement split product C3c in saliva as biomarker for periodontitis and response to periodontal treatment. J Periodontal Res. 2021;56(1):27-33.
Bartold PM, Van Dyke TE. Host modulation: controlling the inflammation to control the infection. Periodontol. 2017;75(1):317-329.
World Medical Association General Assembly. World medical association declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194.
Caton JG, Armitage G, Berglundh T, et al. A new classification scheme for periodontal and peri-implant diseases and conditions-introduction and key changes from the 1999 classification. J Periodontol. 2018;89(Suppl 1):S1-S8.
Cheng WC, van Asten SD, Burns LA, et al. Periodontitis-associated pathogens P. gingivalis and A. actinomycetemcomitans activate human CD14(+) monocytes leading to enhanced Th17/IL-17 responses. Eur J Immunol. 2016;46(9):2211-2221.
Remmele W, Stegner HE. Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue. Pathologe. 1987;8(3):138-140.
Fraga TR, Isaac L, Barbosa AS. Complement evasion by pathogenic Leptospira. Front Immunol. 2016;7:623.
Ricklin D, Reis ES, Lambris JD. Complement in disease: a defence system turning offensive. Nat Rev Nephrol. 2016;12(7):383-401.
Xiang X, Sowa MG, Iacopino AM, et al. An update on novel non-invasive approaches for periodontal diagnosis. J Periodontol. 2010;81(2):186-198.
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):1208.
Grant MM, Taylor JJ, Jaedicke K, et al. Discovery, validation, and diagnostic ability of multiple protein-based biomarkers in saliva and gingival crevicular fluid to distinguish between health and periodontal diseases. J Clin Periodontol. 2022;49(7):622-632.
Ebersole JL, Nagarajan R, Akers D, Miller CS. Targeted salivary biomarkers for discrimination of periodontal health and disease(s). Front Cell Infect Microbiol. 2015;5:62.
Bostanci N, Bao K. Contribution of proteomics to our understanding of periodontal inflammation. Proteomics. 2017;17(3-4):1500518.
Giannobile WV, Beikler T, Kinney JS, Ramseier CA, Morelli T, Wong DT. Saliva as a diagnostic tool for periodontal disease: current state and future directions. Periodontol. 2009;50:52-64.