Diseases of complement dysregulation-an overview

Semin Immunopathol. 2018 Jan;40(1):49-64. doi: 10.1007/s00281-017-0663-8. Epub 2018 Jan 11.

Abstract

Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of complement dysregulation. Although complement overactivation is common to all, cell surface alternative pathway dysregulation (aHUS), fluid phase alternative pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates resulting in the very different phenotypes seen in these diseases. The mechanism underlying the dysregulation also varies with predominant acquired autoimmune (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS) predisposing to disease. Eculizumab has revolutionized the treatment of PNH and aHUS although has been less successful in C3G. With the next generation of complement therapeutic in late stage development, these archetypal complement diseases will provide the initial targets.

Keywords: C3G, aHUS; Complement; PNH.

Publication types

  • Review

MeSH terms

  • Animals
  • Atypical Hemolytic Uremic Syndrome / diagnosis
  • Atypical Hemolytic Uremic Syndrome / etiology
  • Atypical Hemolytic Uremic Syndrome / metabolism
  • Atypical Hemolytic Uremic Syndrome / therapy
  • Complement Activation / genetics
  • Complement Activation / immunology*
  • Complement C3 / immunology
  • Complement C3 / metabolism
  • Complement System Proteins / genetics
  • Complement System Proteins / immunology*
  • Complement System Proteins / metabolism
  • Disease Susceptibility / immunology*
  • Genetic Predisposition to Disease
  • Glomerulonephritis / etiology
  • Glomerulonephritis / metabolism
  • Glomerulonephritis / pathology
  • Hemoglobinuria, Paroxysmal / diagnosis
  • Hemoglobinuria, Paroxysmal / etiology
  • Hemoglobinuria, Paroxysmal / metabolism
  • Hemoglobinuria, Paroxysmal / therapy
  • Humans
  • Molecular Targeted Therapy
  • Phenotype

Substances

  • Complement C3
  • Complement System Proteins