RSS-Feed abonnieren
DOI: 10.1055/a-2077-3544
Functional Consequences of Antibodies against Noncatalytic B Subunit of Factor XIII
Funding Debreceni Egyetem; OTKA Bridging Fund 2022![](https://www.thieme-connect.de/media/10.1055-s-00035024/202309/lookinside/thumbnails/10-1055-a-2077-3544_23040144-1.jpg)
Plasma factor XIII (FXIII) is a zymogen protransglutaminase consisting of two catalytic A (FXIII-A) and two noncatalytic B subunits (FXIII-B). In the plasma, the heterotetramer complex (FXIII-A2B2) is bound to fibrinogen via FXIII-B.[1] Upon activation by thrombin and Ca2+, activated subunit A remains bound to the fibrin fibers and exerts its crosslinking activity, while FXIII-B dissociates from the fibrin.[2] Activated FXIII covalently crosslinks fibrin γ-chains, polymerizes fibrin α-chains, and crosslinks α2-plasmin inhibitor to fibrin α-chains to protect the clot from premature elimination. For a long time, it was thought that the function of the B subunit was merely limited to the prolongation of the lifetime of the A subunit in circulation and to the prevention of its spontaneous nonproteolytic activation. Recently, it was demonstrated that FXIII-B accelerates fibrin crosslinking via the localization of FXIII-A to the D-domain of fibrinogen, which is responsible for γ-chain crosslinking.[2]
In this issue of Thrombosis and Haemostasis, Souri and colleagues present a detailed biochemical characterization of an anti-FXIII-B alloantibody, which was developed in an FXIII-B-deficient patient as a result of repeated plasma-derived FXIII concentrate substitution therapy.[3] Alloantibody of the patient turned out to be polyclonal as it exhibited binding to several individual Sushi domains of FXIII-B. The alloantibodies did not affect the activity of previously activated FXIII-A, however, inhibited the cleavage of the activation peptide from FXIII-A and fibrin crosslinking in an A2B2 heterotetramer-dependent manner. These antibodies also inhibited the A2B2 heterotetramer assembly and binding to fibrinogen, which, in light of the previously reported results in the literature, can be well explained by the presence of antibodies specific for the first and 10th Sushi domains.
Until now, auto- and alloantibodies against FXIII-B were classified as nonneutralizing antibodies; however, based on these results, they may also have a neutralizing effect, indirectly, by inhibiting binding of the heterotetramer complex to fibrinogen.
Publikationsverlauf
Eingereicht: 14. April 2023
Angenommen: 17. April 2023
Accepted Manuscript online:
19. April 2023
Artikel online veröffentlicht:
12. Mai 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
-
References
- 1 Siebenlist KR, Meh DA, Mosesson MW. Plasma factor XIII binds specifically to fibrinogen molecules containing gamma chains. Biochemistry 1996; 35 (32) 10448-10453
- 2 Souri M, Osaki T, Ichinose A. The non-catalytic B subunit of coagulation factor XIII accelerates fibrin cross-linking. J Biol Chem 2015; 290 (19) 12027-12039
- 3 Souri M, Yokoyama C, Osaki T, Ichinose A. Antibodies against non-catalytic B subunit of factor XIII inhibit activation of factor XIII and fibrin crosslinking. Thromb Haemost 2023; 123 (09) 842-855