Exploring the Function of Factor XIII Free B Subunit: Interactions with Complement Factors and a Novel Approach to Identify Potential Binding Partners

Overview

Journal Res Pract Thromb Haemost

Publisher Elsevier

Date 2022 Jul 25

PMID 35873217

Authors

Bojun Li

Clement Bechtler

Lorenz Jenny

Daniel Ricklin

Verena Schroeder

Affiliations

Soon will be listed here.

Abstract

Background: The factor XIII (FXIII)-B subunit has a critical function as a carrier protein to stabilize FXIII-A in plasma and supply it to its main substrate, fibrinogen. However, the function of the excess free FXIII-B circulating in plasma is still elusive.

Objectives: In the present study, we explored potential interactions of free FXIII-B with complement factors and searched for novel binding partners.

Methods: We tested for cofactor activity in the degradation of complement C3b and C4b and used ELISA- and surface plasmon resonance-based binding assays to investigate interactions between FXIII-B and complement components. We performed immunoprecipitation and mass spectrometry analysis to identify potential binding partners of free FXIII-B in freshly drawn plasma samples.

Results: FXIII-B did not exhibit cofactor activity in the degradation of C3b and C4b similar to factor H and C4b-binding protein, nor did it bind to complement factors to a relevant extent. Identification of proteins potentially binding to free FXIII-B revealed high interindividual variation. We confirmed α-macroglobulin (α2MG) as a candidate, although direct interactions or functional effects remain to be validated.

Conclusions: Our study reveals that free FXIII-B has no direct role in regulating the complement system, despite a structural similarity to major complement regulators. Further studies are needed to validate α2MG as a binding partner and explore potential functional consequences of this binding.

Citing Articles

Exploring the function of factor XIII free B subunit: Interactions with complement factors and a novel approach to identify potential binding partners.

Li B, Bechtler C, Jenny L, Ricklin D, Schroeder V Res Pract Thromb Haemost. 2022; 6(5):e12766.

PMID: 35873217 PMC: 9301527. DOI: 10.1002/rth2.12766.

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