title: Dramatic effects of eculizumab in a child with diffuse proliferative lupus nephritis resistant to conventional therapy.
abstract: BACKGROUND
  Treatment of systemic lupus erythematosus (SLE) with severe diffuse proliferative nephritis is often challenging, particularly in small children in whom a genetic conditioning is likely to play a role. The effectiveness of standard therapy based on glucocorticoid and immunosuppressive drugs is often unsatisfactory.
  
  
  METHODS
  A 4 year-old girl, whose parents were first-grade cousins of Moroccan ancestry, developed SLE that progressed to severe renal involvement despite standard therapy. She had persistently undetectable serum C4 levels and very low C3 levels (<30 mg/dl), and extremely high anti-DNA titers (>1:640) that remained unmodified during 2 years of follow-up. No mutations of genes encoding for complement inhibitors were detected. Despite aggressive therapy based on prednisone, plasma exchanges, and cyclosporine, the child worsened and eventually developed features of atypical hemolytic uremic syndrome (aHUS). Treatment with eculizumab provided prompt remission of vasculitis, proteinuria, and hematuria, with normalization of renal function. Two attempts to withdraw eculizumab were followed by severe relapses and rescued by reinstating treatment. The child has been treated with eculizumab for > 17 months without relevant side effects.
  
  
  CONCLUSIONS
  C5 inhibition by eculizumab completely reversed clinical symptoms and laboratory renal signs of severe lupus nephritis. Blocking complement-system activation with the use of targeted drugs may be a new and exciting strategy to treat SLE patients unresponsive to conventional therapy.
authors.affiliation: Nephrology, Dialysis and Transplantation, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy, rosanna.coppo@unito.it.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Coppo
authors.forename: Licia
authors.initials: L
authors.lastname: Peruzzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amore
authors.forename: Silvana
authors.initials: S
authors.lastname: Martino
authors.forename: Luca
authors.initials: L
authors.lastname: Vergano
authors.forename: Inna
authors.initials: I
authors.lastname: Lastauka
authors.forename: Arrigo
authors.initials: A
authors.lastname: Schieppati
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
authors.forename: Pier Angelo
authors.initials: PA
authors.lastname: Tovo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C481642:eculizumab