title: Alloantibody developed in a factor XIII A subunit deficient patient during substitution therapy; characterization of the antibody.
abstract: BACKGROUND
  In factor XIII A subunit (FXIIIA) deficiency, the development of alloantibodies is extremely rare. Only four reports have been published and the antibodies were not characterized.
  
  
  OBJECTIVE
  The aim of this study was to describe the clinical course and the laboratory diagnosis of a FXIII-A deficient patient who developed alloantibodies.
  
  
  METHODS
  FXIII activity was assessed with an ammonia release assay. FXIII-A, FXIII B subunit (FXIII-B) and the complex plasma FXIII (FXIII-A2B2) antigens were determined by ELISA. The causative mutation was detected by fluorescent DNA sequencing. The binding of alloantibody to FXIII-A2and FXIII-A2B2was studied by surface plasmon resonance. The cleavage of FXIII-A by thrombin and Ca2+-induced activation of thrombin-cleaved FXIII were followed by western blotting and activity measurement, respectively.
  
  
  RESULTS
  FXIII activity, FXIII-A2B2and FXIII-A antigens were below the limit of detection in the patient's plasma. The severe FXIII-A deficiency was due to a novel homozygous mutation resulting in early stop codon (c.127C>T, p.Gln42STOP). The alloantibody bound to FXIII-A2and FXIII-A2B2with equally high affinity (Kd~10-8). It accelerated the elimination of administered FXIII concentrate from the circulation, interfered with thrombin and Ca2+-induced activation and inhibited FXIII activity. Attempts to eliminate the alloantibody resulted only in transient improvement. Patient developed intracerebral haemorrhage after a minor trauma and died in spite of aggressive replacement therapy with FXIII concentrate.
  
  
  CONCLUSIONS
  The anti-FXIII-A alloantibody caused an unmanageable bleeding complication. The antibody was of combined subtype which accelerated the elimination of FXIII and exerted a multiple inhibitory effect on FXIII activation/activity.
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Pénzes
authors.affiliation: CHU Sainte-Justine, Montréal, QC, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Vezina
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Bereczky
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: É
authors.initials: É
authors.lastname: Katona
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Kun
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.|Vascular Biology, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Muszbek
authors.affiliation: CHU Sainte-Justine, Montréal, QC, Canada.
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
keywords: FXIII; acquired FXIII deficiency; alloantibody; bleeding diathesis; inherited FXIII deficiency