Complement component 3 and its activation split-products in saliva associate with periodontitis.
complement component 3
immunology
inflammation and innate immunity
pathogenesis
periodontitis
saliva
Journal
Journal of periodontology
ISSN: 1943-3670
Titre abrégé: J Periodontol
Pays: United States
ID NLM: 8000345
Informations de publication
Date de publication:
09 2022
09 2022
Historique:
revised:
25
01
2022
received:
22
09
2021
accepted:
25
01
2022
pubmed:
27
2
2022
medline:
24
9
2022
entrez:
26
2
2022
Statut:
ppublish
Résumé
Periodontitis (PD) is classified by Grades A through C according to the risk of further progression, PD Grade C (PD-C) being the most severe progressing form. It is a matter of controversy, whether the disease activity observed in PD-C is due to impaired immune reactivity toward bacteria embedded in biofilms or a hyper-reactive immune response causing tissue damage as a bystander phenomenon. Little is known about the role of complement in this respect. Plasma and unstimulated saliva samples were collected from patients with PD-B (n = 34) or -C (n = 27) and healthy controls (HCs) (n = 28). Salivary and plasma levels of total C3, C3c, and C3dg were quantified using sandwich enzyme-linked immunosorbent assay (ELISA). Salivary levels of total C3 and C3dg were elevated in PD-B and PD-C patients compared to HCs (both P < 0.05), while the levels of C3c were elevated in PD-C compared to HCs. Plasma levels of C3c were higher in PD-B patients than in HCs (P < 0.05). PD-B and PD-C patients show increased complement activation compared to HCs, but no difference was found between the two disease grades. PD-B, but not PD-C, is associated with increased systemic complement activation as assessed by C3c in plasma.
Sections du résumé
BACKGROUND
Periodontitis (PD) is classified by Grades A through C according to the risk of further progression, PD Grade C (PD-C) being the most severe progressing form. It is a matter of controversy, whether the disease activity observed in PD-C is due to impaired immune reactivity toward bacteria embedded in biofilms or a hyper-reactive immune response causing tissue damage as a bystander phenomenon. Little is known about the role of complement in this respect.
METHODS
Plasma and unstimulated saliva samples were collected from patients with PD-B (n = 34) or -C (n = 27) and healthy controls (HCs) (n = 28). Salivary and plasma levels of total C3, C3c, and C3dg were quantified using sandwich enzyme-linked immunosorbent assay (ELISA).
RESULTS
Salivary levels of total C3 and C3dg were elevated in PD-B and PD-C patients compared to HCs (both P < 0.05), while the levels of C3c were elevated in PD-C compared to HCs. Plasma levels of C3c were higher in PD-B patients than in HCs (P < 0.05).
CONCLUSION
PD-B and PD-C patients show increased complement activation compared to HCs, but no difference was found between the two disease grades. PD-B, but not PD-C, is associated with increased systemic complement activation as assessed by C3c in plasma.
Identifiants
pubmed: 35218227
doi: 10.1002/JPER.21-0530
doi:
Substances chimiques
Complement C3
0
Complement C3c
80295-44-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1294-1301Informations de copyright
© 2022 American Academy of Periodontology.
Références
Eke PI, Thornton-Evans GO, Wei L, et al. Periodontitis in US Adults: national Health and Nutrition Examination Survey 2009-2014. J Am Dent Assoc. 2018;149:576-588e576. https://doi.org/10.1016/j.adaj.2018.04.023.
Bartold PM, Van Dyke TE. Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontol 2000. 2013;62:203-217. https://doi.org/10.1111/j.1600-0757.2012.00450.x.
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. https://doi.org/10.1002/JPER.18-0157.
Papapanou PN, Sanz M, Buduneli N, 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-S182. https://doi.org/10.1002/JPER.17-0721.
Toneti MS, Jung RE, Avila-Ortiz G, et al. Management of the extraction socket and timing of implant placement: consensus report and clinical recommendations of group 3 of the XV European Workshop in Periodontology. J Clin Periodontol. 2019;46 Suppl 21:183-194. https://doi.org/10.1111/jcpe.13131.
Hajishengallis G, Maekawa T, Abe T, et al. Complement Involvement in Periodontitis: molecular Mechanisms and Rational Therapeutic Approaches. Adv Exp Med Biol. 2015;865:57-74. https://doi.org/10.1007/978-3-319-18603-0_4.
Forner L, Larsen T, Kilian M, Holmstrup P. Incidence of bacteremia after chewing, tooth brushing and scaling in individuals with periodontal inflammation. J Clin Periodontol. 2006;33:401-407. https://doi.org/10.1111/j.1600-051X.2006.00924.x.
Damgaard C, Danielsen AK, Enevold C, et al. Circulating antibodies against leukotoxin A as marker of periodontitis Grades B and C and oral infection with Aggregatibacter actinomycetemcomitans. J Periodontol. 2021;92:1795-1804. https://doi.org/10.1002/JPER.20-0895.
Hajishengallis G, Liang S, Payne MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10:497-506. https://doi.org/10.1016/j.chom.2011.10.006.
Janssen BJ, Huizinga EG, Raaijmakers HC, et al. Structures of complement component C3 provide insights into the function and evolution of immunity. Nature. 2005;437:505-511. https://doi.org/10.1038/nature04005.
Davis AE 3rd, Harrison RA, Lachmann PJ. Physiologic inactivation of fluid phase C3b: isolation and structural analysis of C3c, C3d,g (alpha 2D), and C3g. J Immunol. 1984;132:1960-1966.
Troldborg A, Halkjaer L, Pedersen H, et al. Complement activation in human autoimmune diseases and mouse models; employing a sandwich immunoassay specific for C3dg. J Immunol Methods. 2020;486:112866. https://doi.org/10.1016/j.jim.2020.112866.
Schenkein HA, Genco RJ. Gingival fluid and serum in periodontal diseases. I. Quantitative study of immunoglobulins, complement components, and other plasma proteins. J Periodontol. 1977;48:772-777. https://doi.org/10.1902/jop.1977.48.12.772.
Lally ET, McArthur WP, Baehni PC. Biosynthesis of complement components in chronically inflamed gingiva. J Periodontal Res. 1982;17:257-262. https://doi.org/10.1111/j.1600-0765.1982.tb01152.x.
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;10:19-27. https://doi.org/10.1111/j.1600-0765.1975.tb00003.x.
Athina A, Papaconstantinou N, Johannessen AC, Kristoffersen T. Deposits of immunoglobulins, complement, and immune complexes in inflamed human gingiva. Acta Odontologica Scandinavica. 1987;45:187-193. https://doi.org/10.3109/00016358709098858.
Toto PD, Lin L, Gargiulo A. Identification of C3a, IgG, IgM in inflamed human gingiva. J Dent Res. 1978;57:696. https://doi.org/10.1177/00220345780570050501.
Maekawa T, Abe T, Hajishengallis E, et al. Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol. 2014;192:6020-6027. https://doi.org/10.4049/jimmunol.1400569.
Grande MA, Belstrom D, Damgaard C, et al. Salivary concentrations of macrophage activation-related chemokines are influenced by non-surgical periodontal treatment: a 12-week follow-up study. J Oral Microbiol. 2020;12:1694383. https://doi.org/10.1080/20002297.2019.1694383.
Rautemaa R, Meri S. Protection of gingival epithelium against complement-mediated damage by strong expression of the membrane attack complex inhibitor protectin (CD59). J Dent Res. 1996;75:568-574. https://doi.org/10.1177/00220345960750010901.
Asakawa R, Komatsuzawa H, Kawai T, et al. Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans. Mol Microbiol. 2003;50:1125-1139. https://doi.org/10.1046/j.1365-2958.2003.03748.x.
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;20:268-275. https://doi.org/10.1111/j.1600-0765.1985.tb00434.x.
Rasmussen KJ, Skjoedt MO, Vitved L, et al. A novel antihuman C3d monoclonal antibody with specificity to the C3d complement split product. J Immunol Methods. 2017;444:51-55. https://doi.org/10.1016/j.jim.2017.02.002.
Van der Velden U. What exactly distinguishes aggressive from chronic periodontitis: is it mainly a difference in the degree of bacterial invasiveness? Periodontol 2000. 2017;75:24-44. https://doi.org/10.1111/prd.12202.
Shapira L, Borinski R, Sela MN, et al. Superoxide formation and chemiluminescence of peripheral polymorphonuclear leukocytes in rapidly progressive periodontitis patients. J Clin Periodontol. 1991;18:44-48. https://doi.org/10.1111/j.1600-051x.1991.tb01118.x.
Leino L, Hurttia HM, Sorvajarvi K, et al. Increased respiratory burst activity is associated with normal expression of IgG-Fc-receptors and complement receptors in peripheral neutrophils from patients with juvenile periodontitis. J Periodontal Res. 1994;29:179-184. https://doi.org/10.1111/j.1600-0765.1994.tb01211.x.
Shibata K, Warbington ML, Gordon BJ, et al. Nitric oxide synthase activity in neutrophils from patients with localized aggressive periodontitis. J Periodontol. 2001;72:1052-1058. https://doi.org/10.1902/jop.2001.72.8.1052.
Kantarci A, Oyaizu K, Van Dyke TE. Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. J Periodontol. 2003;74:66-75. https://doi.org/10.1902/jop.2003.74.1.66.
Damgaard C, Danielsen AK, Enevold C, et al. Porphyromonas gingivalis in saliva associates with chronic and aggressive periodontitis. J Oral Microbiol. 2019;11:1653123. https://doi.org/10.1080/20002297.2019.1653123.
Armitage GC. Development of a classification system for periodontal diseases and conditions. Ann Periodontol. 1999;4:1-6. https://doi.org/10.1902/annals.1999.4.1.1.
Chapple ILC, Mealey BL, Van Dyke TE, 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. https://doi.org/10.1002/JPER.17-0719.
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;56:27-33. https://doi.org/10.1111/jre.12788.
Aurer A, Jorgic-Srdjak K, Plancak D, et al. Proinflammatory factors in saliva as possible markers for periodontal disease. Coll Antropol. 2005;29:435-439.
Phillips CM, Kesse-Guyot E, Ahluwalia N, et al. Dietary fat, abdominal obesity and smoking modulate the relationship between plasma complement component 3 concentrations and metabolic syndrome risk. Atherosclerosis. 2012;220:513-519. https://doi.org/10.1016/j.atherosclerosis.2011.11.007.
Weinstein A, Alexander RV, Zack DJ. A review of complement activation in SLE. Curr Rheumatol Rep. 2021;23(3):16. https://doi.org/10.1007/s11926-021-00984-1.