title: Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15.
abstract: Quantitative or functional deficiency of complement factor H results in uncontrolled complement activation. This leads to thrombotic microangiopathy and finally causes renal failure (atypical hemolytic uremic syndrome [aHUS]). By regular analysis of factor H in patients with aHUS, the authors found a complete factor H deficiency in an infant in whom aHUS developed at 8 months of age. Factor H was quantified by enzyme-linked immunosorbent assay and further analyzed by Western blot using a factor H-specific antibody. Complement activation was determined by measuring total hemolytic activity of the classical (CH50) and alternative (APH50) pathways, C3 and C3d. The sequence of factor H gene was determined. Serial factor H measurements after fresh frozen plasma infusion allowed calculation of a factor H half-life. Factor H was absent in plasma (<1 mug/mL), and the complement system was highly activated (CH50, APH50, C3 decreased; C3d increased). Genetic analysis identified a novel homozygous factor H mutation (T2770A; Y899Stop) in CCP domain 15, most likely causing defective protein secretion. Time course measurements of factor H after plasma infusion established a factor H half-life of about 6 days. By repetitive plasma infusions (20 mL/kg over about 2 to 3 hours) the authors were able to interrupt the vicious circle of thrombotic microangiopathy in a factor H-deficient patient with aHUS. Based on the measured factor H half-life of about 6 days, regular plasma infusions in 2-week intervals were given, which prevented further aHUS episodes and stopped the decline of kidney function.
authors.affiliation: Division of Pediatric Nephrology, Children's Hospital of the University of Cologne, Cologne, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Licht
authors.forename: Annic
authors.initials: A
authors.lastname: Weyersberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Heinen
authors.forename: Ludwig
authors.initials: L
authors.lastname: Stapenhorst
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Devenge
authors.forename: Bodo
authors.initials: B
authors.lastname: Beck
authors.forename: Ruediger
authors.initials: R
authors.lastname: Waldherr
authors.forename: Michael
authors.initials: M
authors.lastname: Kirschfink
authors.forename: Peter F
authors.initials: PF
authors.lastname: Zipfel
authors.forename: Bernd
authors.initials: B
authors.lastname: Hoppe
mesh_terms: D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics*; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics*; D010455:Peptides / Q000235:genetics*; D010951:Plasma Exchange / Q000379:methods*; D017434:Protein Structure, Tertiary / Q000235:genetics
chemical_list: C493495:CFH protein, human; D010455:Peptides; D017242:Complement Factor H