1. Antibodies against Noncatalytic B Subunit of Factor XIII Inhibit Activation of Factor XIII and Fibrin Crosslinking.
- Author
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Souri M, Yokoyama C, Osaki T, and Ichinose A
- Subjects
- Humans, Rats, Animals, Fibrin metabolism, Isoantibodies, Factor XIIIa metabolism, Antibodies, Monoclonal pharmacology, Peptides, Factor XIII metabolism, Factor XIII Deficiency
- Abstract
Background: Coagulation factor XIII (FXIII) is a proenzyme of plasma transglutaminase. It comprises two catalytic A subunits (FXIII-A) and two carrier B subunits (FXIII-B). We previously reported that alloantibodies against FXIII-B could promote FXIII clearance in a patient with congenital FXIII-B deficiency who had received infusions of plasma-derived human FXIII (A
2 B2 heterotetramer)., Objectives: We aimed to investigate whether anti-FXIII-B antibodies affect the catalytic function of FXIII., Methods: FXIII activation and fibrin crosslinking were examined in the presence of patient plasma, isolated patient IgG, or rat anti-FXIII-B monoclonal antibodies., Results: Alloantibody levels were increased by repeated infusions of plasma-derived A2 B2 heterotetramer, which enhanced binding to the functionally important FXIII-B sushi domains. The patient plasma strongly inhibited cleavage of the FXIII-A activation peptide, amine incorporation, and fibrin crosslinking in normal plasma. Furthermore, anti-FXIII-B alloantibodies blocked the formation of the complex of FXIII-B with FXIII-A, and fibrinogen. Rat monoclonal antibodies against the 10th sushi domain of FXIII-B inhibited the incorporation of FXIII-B to fibrin, FXIII activation (i.e., cleavage of FXIII-A activation peptide), and ultimately fibrin crosslinking in normal plasma, independent of their effect on heterotetramer assembly with FXIII-A. Alloantibody binding to the A2 B2 heterotetramer blocked the access of thrombin to the FXIII-A cleavage site, as indicated by the reaction of the alloantibodies to the A2 B2 heterotetramer and FXIII-B, but not to FXIII-A., Conclusion: Anti-FXIII-B antibodies binding to the A2 B2 heterotetramer and FXIII-B inhibited FXIII activation and its crosslinking function despite being directed against its noncatalytic subunit (FXIII-B)., Competing Interests: None declared., (Thieme. All rights reserved.)- Published
- 2023
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