title: Severe bleeding diatheses in an elderly patient with combined type autoantibody against factor XIII A subunit; novel approach to the diagnosis and classification of anti-factor XIII antibodies.
abstract: BACKGROUND
  Acquired factor XIII (FXIII) deficiency due to autoantibody is a rare, severe bleeding diathesis. Its laboratory diagnosis and classification represents a difficult task.
  
  
  OBJECTIVE
  Introduction of novel approaches into the diagnosis and characterization of anti-FXIII autoantibody and demonstration of their use in the diagnosis of a patient with autoimmune FXIII deficiency.
  
  
  METHODS
  Factor XIII activity, FXIII antigen levels and the titre of anti-FXIII-A antibody were monitored throughout the course of the disease. FXIII activity was measured by ammonia release assay; FXIII-A2B2complex, total and free FXIII-B concentrations were determined by ELISAs. The binding constant for the interaction of the autoantibody with recombinant FXIII-A2(rFXIII-A2) and FXIII-A2B2was determined by surface plasmon resonance (SPR). The inhibitory capacity of IgG was expressed as the concentration exerting 50% inhibition of FXIII activation/activity (IC50). The truncation of FXIII-A by thrombin was monitored by western blotting. The inhibition of Ca2+-induced FXIII activation and active FXIII (FXIIIa) were assessed by FXIII activity assay.
  
  
  RESULTS
  The antibody bound to rFXIII-A2and FXIII-A2B2with high affinity and accelerated the decay of supplemented FXIII concentrate. An IC50 value of 170.1 μg IgG·mL-1indicated effective FXIII neutralization. The main neutralizing effect of the autoantibody was the inhibition of FXIIIa. After 2 months, due to combined therapeutic modalities, the autoantibody disappeared and FXIII activity significantly elevated.
  
  
  CONCLUSIONS
  The anti-FXIII-A autoantibody exerted a combined effect including inhibition of FXIIIa and acceleration of FXIII decay in the plasma. IC50 and binding constant determinations added important information to the characterization of the autoantibody.
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Kun
authors.affiliation: CHU Sainte-Justine, Montréal, Quebec, Canada.
authors.forename: N
authors.initials: N
authors.lastname: Szuber
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, 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, 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: K
authors.initials: K
authors.lastname: Pénzes
authors.affiliation: CHU Sainte-Justine, Montréal, Quebec, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Bonnefoy
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: B
authors.initials: B
authors.lastname: Bécsi
authors.affiliation: Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: F
authors.initials: F
authors.lastname: Erdődi
authors.affiliation: CHU Sainte-Justine, Montréal, Quebec, Canada.
authors.forename: G E
authors.initials: GE
authors.lastname: Rivard
authors.affiliation: Division of Clinical Laboratory Science, Department of Laboratory Medicine, 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.identifier: http://orcid.org/0000-0002-3798-9962
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology*; D004198:Disease Susceptibility; D005176:Factor XIII / Q000276:immunology*; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D021122:Protein Subunits / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D021122:Protein Subunits; D005176:Factor XIII
keywords: acquired FXIII deficiency; antibody classification; autoantibody; binding affinity; bleeding diathesis; factor XIII