title: Complete factor I deficiency due to dysfunctional factor I with recurrent aseptic meningo-encephalitis.
abstract: OBJECTIVE
  Complement regulators control the activated complement system. Defects in this homeostasis can result in tissue damage and autoimmune diseases with a heterogeneity in clinical presentation. Complement factor I (FI), a serine protease, is an important regulator of alternative pathway activation. We report a diagnostic work-up of a patient with relapsing inflammatory mediated meningo-encephalitis. Our work-up revealed a rare genetic factor I (FI) deficiency. So far, all cases of reported complete factor I deficiency have absent serum levels of FI. We present here a unique case of a complete factor I deficiency based on a functional FI defect.
  
  
  METHODS
  Complement assays and measurement of FI activity were performed in the patient, her family, factor H-deficient patients, a patient with C3-nephritic factor and 11 healthy controls. Genetic sequencing of the FI coding regions in the patient and her parents was performed.
  
  
  RESULTS
  The patient had absent alternative pathway activity with low levels of C3 and normal serum level of FI. The patient's plasma FI did not degrade C3b, with normalisation of C3b degradation after adding purified FI. Mutation analysis of the complement factor I gene revealed two heterozygous mutations (I322T and D506V).
  
  
  CONCLUSIONS
  To our knowledge, this paper describes a complete FI deficiency caused by a defect of FI activity for the first time. Normal FI concentration does not exclude a complete FI defect, additional functional analysis of FI is required in any patient with a defect of complement activation. Recurrent aseptic meningo-encephalitis is a rare clinical presentation of complete FI deficiency.
authors.affiliation: Pediatric Pulmonology and Immunology, Ghent University Hospital, 9000, Ghent, Belgium, filomeen.haerynck@Ugent.be.
authors.forename: Filomeen
authors.initials: F
authors.lastname: Haerynck
authors.forename: Patrick
authors.initials: P
authors.lastname: Stordeur
authors.forename: Johan
authors.initials: J
authors.lastname: Vandewalle
authors.forename: Rudy
authors.initials: R
authors.lastname: Van Coster
authors.forename: Victoria
authors.initials: V
authors.lastname: Bordon
authors.forename: Frans
authors.initials: F
authors.lastname: De Baets
authors.forename: Petra
authors.initials: P
authors.lastname: Schelstraete
authors.forename: Cédric
authors.initials: C
authors.lastname: Javaux
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Bouvry
authors.forename: Véronique
authors.initials: V
authors.lastname: Fremeaux-Bacchi
authors.forename: Joke
authors.initials: J
authors.lastname: Dehoorne
mesh_terms: D003167:Complement Activation / Q000235:genetics / Q000276:immunology; D017244:Complement Factor I / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D006461:Hemolysis / Q000235:genetics / Q000276:immunology; D006801:Humans; D008582:Meningitis, Aseptic / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D008590:Meningoencephalitis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012008:Recurrence; D017422:Sequence Analysis, DNA
chemical_list: D017244:Complement Factor I