title: Neutralizing autoantibody against factor XIII A subunit resulted in severe bleeding diathesis with a fatal outcome - characterization of the antibody.
abstract: Essentials Autoantibody against factor XIII (FXIII) is a rare but severe acquired hemorrhagic diathesis. In an elderly patient, anti-FXIII-A antibody led to severe bleedings with fatal outcome. The neutralizing autoantibody bound to FXIII with high affinity (Ka≈10(9) m(-1) ). The dominant effect of the autoantibody was the inhibition of activated FXIII.
  
  
  
  Autoantibodies may develop against the catalytic A subunit of factor XIII (FXIII-A) or the carrier B subunit (FXIII-B). Autoimmune FXIII-A deficiency was diagnosed in an elderly (75 years) patient with severe bleeding symptoms. The patient had 3% FXIII activity, and unmeasurable FXIII-A2 B2 and FXIII-A antigens in the plasma, whereas, in the platelet lysate, activity and FXIII-A antigen values were normal. As revealed by western blotting, FXIII antigen was present in the plasma, but the autoantibody interfered with the immunoassays. A mixing study indicated the presence of inhibitor with a titer of 63.2 Bethesda units (BU). The patient's IgG bound to FXIII-A2 B2 and to FXIII-A2 with equally high affinity (Ka in the range of 10(9) m(-1) ). It exerted a multiple inhibitory effect on FXIII activation/activity (IC50: 50 μg mL(-1) ). Immunosupressive therapy gradually decreased the autoantibody titer to 8.0 BU, but FXIII activity remained very low, and, owing to recurrent bleeding, the patient died.
authors.affiliation: Division of Clinical Laboratory Science, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Pénzes
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Rázsó
authors.affiliation: Division of Clinical Laboratory Science, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: É
authors.initials: É
authors.lastname: Katona
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Kerényi
authors.affiliation: Division of Clinical Laboratory Science, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Kun
authors.affiliation: Division of Clinical Laboratory Science, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.|Vascular Biology, Thrombosis and Hemostasis Research Group of the Hungarian Academy of Sciences, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Muszbek
mesh_terms: D000368:Aged; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001792:Blood Platelets / Q000378:metabolism; D002384:Catalysis; D026122:Factor XIIIa / Q000276:immunology*; D017809:Fatal Outcome; D006470:Hemorrhage / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007166:Immunosuppressive Agents; D007700:Kinetics; D008297:Male; D000072417:Protein Domains; D020349:Surface Plasmon Resonance
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D026122:Factor XIIIa
keywords: blood coagulation disorder; factor XIII; factor XIII deficiency; factor XIIIa; neutralizing antibody