title: Case report: lupus nephritis with autoantibodies to complement alternative pathway proteins and C3 gene mutation.
abstract: BACKGROUND
  Glomerulonephritis is one of the most severe complications of lupus, a systemic disease with multi-organ involvement, with tissue damage produced mainly by complement activation. As a result of this activation, patients with active lupus present hypocomplementemia during disease flares, but C3 and C4 levels are recovered between episodes.
  
  
  METHODS
  We present a patient who suffered two lupus nephritis episodes in 5 years, achieving complete remission with treatment after both of them, but with C3 levels persistently below normal range. Genetic study revealed that the patient carried a mutation in heterozygosis in the C3 gene. Serial sera samples were analyzed, and autoantibodies to complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin) were found. Functional assays showed that these autoantibodies cause alternative pathway activation.
  
  
  CONCLUSIONS
  This case is the first reported of a heterozygous C3 mutation associated with lupus nephritis and autoantibodies against complement alternative pathway proteins (Factor I, Factor B, C3 and Properdin).These autoantibodies cause activation of this pathway and this fact could explain that the tissue damage is restricted to the kidney.
authors.affiliation: Immunology Unit, University Hospital La Paz, IdiPAZ, Madrid, Spain. pilar.nozal@salud.madrid.org.|Unit 754, Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain. pilar.nozal@salud.madrid.org.
authors.forename: Pilar
authors.initials: P
authors.lastname: Nozal
authors.affiliation: Immunology Unit, University Hospital La Paz, IdiPAZ, Madrid, Spain. sofia.garrido@salud.madrid.org.|Unit 754, Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain. sofia.garrido@salud.madrid.org.
authors.forename: Sofía
authors.initials: S
authors.lastname: Garrido
authors.affiliation: Department of Nephrology, University Hospital La Paz, IdiPAZ, Madrid, Spain. jmartinezara@gmail.com.
authors.forename: Jorge
authors.initials: J
authors.lastname: Martínez-Ara
authors.affiliation: Department of Pathological Anatomy, University Hospital, IdiPAZ, Madrid, Spain. mluz.picazo@salud.madrid.org.
authors.forename: María Luz
authors.initials: ML
authors.lastname: Picazo
authors.affiliation: Department of Pathological Anatomy, University Hospital, IdiPAZ, Madrid, Spain. laura.yebenes@salud.madrid.org.
authors.forename: Laura
authors.initials: L
authors.lastname: Yébenes
authors.affiliation: Immunology Unit, University Hospital La Paz, IdiPAZ, Madrid, Spain. ritafrancisca.alvarez@salud.madrid.org.
authors.forename: Rita
authors.initials: R
authors.lastname: Álvarez-Doforno
authors.affiliation: Biological Research Center, CSIC, Madrid, Spain. spinto@cib.csic.es.|Unit 738, Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain. spinto@cib.csic.es.
authors.forename: Sheila
authors.initials: S
authors.lastname: Pinto
authors.affiliation: Biological Research Center, CSIC, Madrid, Spain. SrdeCordoba@cib.csic.es.|Unit 738, Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain. SrdeCordoba@cib.csic.es.
authors.forename: Santiago Rodríguez
authors.initials: SR
authors.lastname: de Córdoba
authors.affiliation: Immunology Unit, University Hospital La Paz, IdiPAZ, Madrid, Spain. mltrascasa@salud.madrid.org.|Unit 754, Center for Biomedical Research on Rare Diseases (CIBERER), Madrid, Spain. mltrascasa@salud.madrid.org.
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D003176:Complement C3 / Q000235:genetics* / Q000276:immunology; D011415:Complement Factor B / Q000276:immunology; D005260:Female; D005340:Fibrinogen / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D007668:Kidney / Q000473:pathology*; D008181:Lupus Nephritis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D009154:Mutation; D011414:Properdin / Q000276:immunology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D003176:Complement C3; D011414:Properdin; D005340:Fibrinogen; D011415:Complement Factor B