MHC class II presentation of FVIII-AnnexinA5 fusion proteins internalized by antigen presenting cells.

ABSTRACT:

Introduction

The development of neutralizing antibodies (inhibitors) against coagulation factor VIII (FVIII) remains the most serious complication in the treatment of hemophilia A. While immune tolerance induction (ITI) is the standard strategy to eliminate these antibodies, it fails in approximately 30% of patients with severe hemophilia A, underscoring the need for innovative approaches to promote FVIII-specific tolerance.

Methods

To address this challenge, we generated fusion proteins composed of A2, A3-C1-C2 (light chain, LCh), and C2 domains of FVIII linked to Annexin A5 (AnxA5), a protein that binds phosphatidylserine (PS), a hallmark of apoptotic cells.

Results

ELISA confirmed high-affinity binding of all fusion proteins to immobilized PS. To model PS exposure

SUBMITTER: Miranda M 

PROVIDER: S-EPMC12507630 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature