title: Complement activation and effect of eculizumab in scleroderma renal crisis.
abstract: BACKGROUND
  Scleroderma renal crisis (SRC) is a life-threatening complication of systemic sclerosis characterized by abrupt onset of hypertension, thrombotic microangiopathy, and kidney injury. The mechanisms of the disease remain ill-defined, but a growing body of evidence suggests that activation of the complement system may be involved.
  
  
  METHODS
  Here, we report the case of a patient presenting with severe SRC and strong evidence of complement activation, both in serum and in the kidney, in the absence of genetic defect of the complement system.
  
  
  RESULTS
  Immunofluorescence studies on kidney biopsy showed significant deposits of C1q and C4d in the endothelium of renal arterioles, pointing toward activation of the classical pathway. Because of the dramatic clinical and histological severity, and the lack of response to early treatment with angiotensin-converting enzyme inhibitors, calcium channel blockers and plasma exchange, the patient was treated with the specific C5 blocker eculizumab.Contrarily to conventional treatment, eculizumab efficiently blocked C5b-9 deposition ex vivo and maintained hematological remission. Unfortunately, the patient died from heart failure a few weeks later. Postmortem examination of the heart showed diffuse patchy interstitial fibrosis, the typical lesion of systemic sclerosis-related cardiomyopathy, but normal coronary arteries and myocardial microvasculature.
  
  
  CONCLUSIONS
  SRC may lead to complement system activation through the classical pathway. Early administration of C5 inhibitor eculizumab may have therapeutic potential in patients with life-threatening SRC refractory to conventional treatment using angiotensin-converting enzyme inhibitors.
authors.affiliation: Division of Nephrology, Cliniques Universitaires Saint-Luc Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain Division of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium Department of Nephrology and Transplantation, Lapeyronie Hospital, Montpellier, France Immunobiology Clinic, Université Libre de Bruxelles-Hôpital Erasme Hemostasis-Thrombosis Unit, Division of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium IRCCS - Istituto di Ricerche Farmacologiche "Mario Negri," Clinical Research Center for Rare Diseases Aldo e Cele Daccò, Ranica, Bergamo, Italy.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Devresse
authors.forename: Selda
authors.initials: S
authors.lastname: Aydin
authors.forename: Moglie
authors.initials: M
authors.lastname: Le Quintrec
authors.forename: Nathalie
authors.initials: N
authors.lastname: Demoulin
authors.forename: Patrick
authors.initials: P
authors.lastname: Stordeur
authors.forename: Catherine
authors.initials: C
authors.lastname: Lambert
authors.forename: Sara
authors.initials: S
authors.lastname: Gastoldi
authors.forename: Yves
authors.initials: Y
authors.lastname: Pirson
authors.forename: Michel
authors.initials: M
authors.lastname: Jadoul
authors.forename: Johann
authors.initials: J
authors.lastname: Morelle
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D001706:Biopsy; D003167:Complement Activation / Q000187:drug effects* / Q000276:immunology*; D015922:Complement C1q / Q000032:analysis; D015935:Complement C4b / Q000032:analysis; D003182:Complement C5 / Q000037:antagonists & inhibitors; D003171:Complement Pathway, Classical / Q000187:drug effects / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007668:Kidney / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000032:analysis; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology*; D011272:Pregnancy, Multiple; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D003182:Complement C5; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d; C481642:eculizumab