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Complement C3 as a Target of Host Modulation in Periodontitis

  • George HajishengallisEmail author
  • Tetsuhiro Kajikawa
  • Evlambia Hajishengallis
  • Tomoki Maekawa
  • Xiaofei Li
  • George N. Belibasakis
  • Nagihan Bostanci
  • Dimitrios C. Mastellos
  • Despina Yancopoulou
  • Hatice Hasturk
  • John D. Lambris
Chapter

Abstract

Although originally identified as a blood-based antimicrobial system, complement is now regarded as a central regulator of immune and inflammatory responses and tissue homeostasis. When dysregulated or overactivated, however, complement can turn from a homeostatic to a pathological effector that drives a number of inflammatory disorders. In this context, destructive periodontal inflammation in humans is correlated with elevated complement activity. Moreover, mechanistic studies in mice have causally linked the central complement component C3 and downstream signaling pathways in the induction of periodontal dysbiosis and inflammation that leads to alveolar bone loss. Consistent with this, pharmacological inhibition of C3 activation by a locally administered drug (Cp40/AMY-101) was shown to suppress both induced and naturally occurring periodontitis in non-human primates. Thus, C3-targeted intervention represents a promising host-modulation approach to treat human periodontitis.

Keywords

Periodontitis Inflammation Bone loss Complement C3 Compstatin AMY-101 Host modulation Therapeutics 

Notes

Acknowledgments

The authors are supported by grants from the U.S. National Institutes of Health (AI068730 and AI030040 to J.D.L.; DE015254, DE024153, and DE024716 to G.H.) and the European Commission (FP7-DIREKT 602699 to J.D.L.).

Conflict of Interest Statement: J.D.L. is the founder of Amyndas Pharmaceuticals, which is developing complement inhibitors (including third-generation compstatin analogs such as AMY-101). J.D.L. and G.H are inventors of patents or patent applications that describe the use of complement inhibitors for therapeutic purposes, some of which are developed by Amyndas Pharmaceuticals. J.D.L. is also the inventor of the compstatin technology licensed to Apellis Pharmaceuticals (i.e., 4(1MeW)7W/POT-4/APL-1 and PEGylated derivatives such as APL-2/pegcetacoplan). The other authors declare no competing interest.

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Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • George Hajishengallis
    • 1
    Email author
  • Tetsuhiro Kajikawa
    • 1
  • Evlambia Hajishengallis
    • 2
  • Tomoki Maekawa
    • 3
  • Xiaofei Li
    • 1
  • George N. Belibasakis
    • 4
  • Nagihan Bostanci
    • 4
  • Dimitrios C. Mastellos
    • 5
  • Despina Yancopoulou
    • 6
  • Hatice Hasturk
    • 7
  • John D. Lambris
    • 8
  1. 1.Department of Basic and Translational Sciences, Penn Dental MedicineUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Division of Pediatric Dentistry, Department of Preventive and Restorative SciencesUniversity of Pennsylvania Penn Dental MedicinePhiladelphiaUSA
  3. 3.Research Center for Advanced Oral Science, Graduate School of Medical and Dental SciencesNiigata UniversityNiigataJapan
  4. 4.Division of Oral Diseases, Department of Dental MedicineKarolinska InstitutetStockholmSweden
  5. 5.Division of Biodiagnostic Sciences and Technologies, INRASTESNational Center for Scientific Research ‘Demokritos’AthensGreece
  6. 6.Amyndas PharmaceuticalsGlyfadaGreece
  7. 7.Center for Clinical and Translational ResearchForsyth InstituteCambridgeUSA
  8. 8.Department of Pathology and Laboratory Medicine, Perelman School of MedicineUniversity of PennsylvaniaPhiladelphiaUSA

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