title: Severe active C3 glomerulonephritis triggered by immune complexes and inactivated after eculizumab therapy.
abstract: BACKGROUND
  Understanding the role of alternative complement pathway dysregulation in membranoproliferative glomerulonephritis (MPGN) has led to a dramatic shift in its classification into two subgroups: immune complex-mediated MPGN and complement-mediated MPGN, consisting of dense deposit disease and C3 glomerulonephritis (C3GN). A limited number of C3GN cases have been published to date with not yet conclusive results since the novel therapeutic approach with eculizumab was introduced.
  
  
  METHODS
  We report the clinical follow-up of a 16-year-old patient in whom a diagnosis of C3GN was confirmed by immunofluorescence and electron microscopy in second and third kidney biopsies, while the first biopsy revealed idiopathic immune complex-mediated MPGN type III, Anders and Strife variant, which failed to improve after several attempts at conventional immunosuppression therapy. Although applied late in an already fairly advanced stage of the severe active form of MPGN, the efficacy of eculizumab on C3GN was evidenced clinically and pathohistologically. Its beneficial influence on pathomorphogenesis was demonstrated by a unique follow-up in the last three biopsies, despite the recent observation, confirmed in this study, of eculizumab binding within the kidney tissue.
  
  
  CONCLUSIONS
  Clinicians and pathologists should be aware that, in some patients, an underlying genetic or acquired complement alternative pathway abnormality can be masked by an initial immune complex-mediated mechanism, which subsequently triggers an unbalanced excessive continual driving of complement terminal pathway activation and the development of C3GN. In such a patient, supplementary steroids in addition to eculizumab appear necessary to achieve an adequate response.
authors.affiliation: Department of Nephrology, Division of Paediatrics, University Medical Centre, Bohoričeva 20, 1000, Ljubljana, Slovenia. tanja.kersnik@guest.arnes.si.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kersnik Levart
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Dušan
authors.initials: D
authors.lastname: Ferluga
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Alenka
authors.initials: A
authors.lastname: Vizjak
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Jerica
authors.initials: J
authors.lastname: Mraz
authors.affiliation: Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Nika
authors.initials: N
authors.lastname: Kojc
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D003176:Complement C3 / Q000276:immunology*; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D003170:Complement Pathway, Alternative / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D015432:Glomerulonephritis, Membranoproliferative / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000276:immunology / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D012074:Remission Induction; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C038245:C3 protein, human; D003176:Complement C3; D051056:Complement Inactivating Agents; C481642:eculizumab
keywords: C3 glomerulonephritis; Complement alternative pathway dysregulation; Eculizumab; Membranoproliferative glomerulonephritis