C-Reactive Protein and Its Structural Isoforms: An Evolutionary Conserved Marker and Central Player in Inflammatory Diseases and Beyond

  • James D. McFadyenEmail author
  • Johannes Zeller
  • Lawrence A. Potempa
  • Geoffrey A. Pietersz
  • Steffen U. Eisenhardt
  • Karlheinz PeterEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 94)


C-reactive protein (CRP) is an evolutionary highly conserved member of the pentraxin superfamily of proteins. CRP is widely used as a marker of inflammation, infection and for risk stratification of cardiovascular events. However, there is now a large body of evidence, that continues to evolve, detailing that CRP directly mediates inflammatory reactions and the innate immune response in the context of localised tissue injury. These data support the concept that the pentameric conformation of CRP dissociates into pro-inflammatory CRP isoforms termed pCRP* and monomeric CRP. These pro-inflammatory CRP isoforms undergo conformational changes that facilitate complement binding and immune cell activation and therefore demonstrate the ability to trigger complement activation, activate platelets, monocytes and endothelial cells. The dissociation of pCRP occurs on the surface of necrotic, apoptotic, and ischaemic cells, regular β-sheet structures such as β-amyloid, the membranes of activated cells (e.g., platelets, monocytes, and endothelial cells), and/or the surface of microparticles, the latter by binding to phosphocholine. Therefore, the deposition and localisation of these pro-inflammatory isoforms of CRP have been demonstrated to amplify inflammation and tissue damage in a broad range of clinical conditions including ischaemia/reperfusion injury, Alzheimer’s disease, age-related macular degeneration and immune thrombocytopaenia. Given the potentially broad relevance of CRP to disease pathology, the development of inhibitors of CRP remains an area of active investigation, which may pave the way for novel therapeutics for a diverse range of inflammatory diseases.


C-reactive protein CRP Inflammation Complement CRP structure Ischaemia/reperfusion injury Alzheimer’s disease Atherosclerosis 



We thank Eliana Stanziano for her excellent manuscript editing and formatting.


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© Springer Nature Switzerland AG 2020

Authors and Affiliations

  • James D. McFadyen
    • 1
    • 2
    • 3
    • 4
    Email author
  • Johannes Zeller
    • 5
  • Lawrence A. Potempa
    • 6
  • Geoffrey A. Pietersz
    • 1
    • 7
    • 8
  • Steffen U. Eisenhardt
    • 5
  • Karlheinz Peter
    • 1
    • 2
    • 7
    • 9
    Email author
  1. 1.Atherothrombosis and Vascular Biology LaboratoryBaker Heart and Diabetes InstituteMelbourneAustralia
  2. 2.Department of MedicineMonash UniversityMelbourneAustralia
  3. 3.Department of Clinical HaematologyThe Alfred HospitalMelbourneAustralia
  4. 4.Australian Centre for Blood Diseases, Monash UniversityMelbourneAustralia
  5. 5.Department of Plastic and Hand Surgery, Medical Faculty of the University of FreiburgUniversity of Freiburg Medical CentreFreiburgGermany
  6. 6.College of PharmacyRoosevelt UniversitySchaumburgUSA
  7. 7.Department of ImmunologyMonash UniversityMelbourneAustralia
  8. 8.Burnet InstituteMelbourneAustralia
  9. 9.Heart Centre, The Alfred HospitalMelbourneAustralia

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