Factor XIII subunit B: a protein A binding protein

Abstract number: P0285

Kerényi A., Haramura G., Muszbek L.

University of Debrecen, Medical and Health Science Center, Hungary; Hungary

Blood coagulation factor XIII (FXIII) is a tetrameric protein consisting of two potentially active A (FXIII-A) and two protective (carrier) B subunits (FXIII-B). FXIII-A is predominantly synthesized by cells of bone marrow origin and FXIII-B is synthesized by hepatocytes. The complex between the two types of subunits is formed in the plasma and FXIII-B prevents FXIII-A from the slow spontaneous activation that would otherwise occur in plasmatic conditions. In the plasma FXIII-B is present in excess and half of FXIII-B circulates as free protein. It has been proposed that FXIII-B has a role additional to its function in the clotting system. Protein A is a Staphylococcal protein is that characteristically binds to the Fc portion of IgG between the CH₂ and CH₃ domains. The protein is involved in defending the microorganism against the destructive potential of the Fc region of IgG. Using ELISA technique in which the microplates were coated by highly purified human FXIII-B, a tight binding of protein A labeled with biotin or peroxidase to FXIII-B was demonstrated. The extent of protein A binding to FXIII-B was comparable the binding to human IgG. Protein A also bound to FXIII-B when FXIII-B was part of the plasma FXIII complex, though to a lesser extent. No binding to FXIII-A could be observed. Anti-human IgG antibody produced in goat or rabbit also bound to FXIII-B and FXIII A2B2 complex, but not to FXIII-A. Anti-mouse IgG produced in rabbit or goat gave hardly any reaction with human FXIII-B and nonimmune IgG did not show any reaction. Reaction with antihuman IgM, antibodies against isolated kappa and lambda chains was significantly less than the reaction with anti human IgG and there was no reaction with antihuman IgG and IgE. The experiments suggest that protein A and antihuman IgG react with an epitope on FXIII-B that is similar to an epitope on human IgG. The reaction of FXIII-B with protein A might interfere with the protective mechanism of Staphylococcus aureus and thus, FXIII-B might participate in the nonspecific antimicrobial defense mechanism of the organism.