Role of B Cells in Breaking and Maintaining Tolerance to Clotting Factor VIII in Congenital and Acquired Hemophilia A

Antibodies

Amanda M. Actor²  Claire K. Holley¹ 

[1] Program in Molecular Pathology, Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston, TX 77030, USA;Department of Pathology and Laboratory Medicine, Medical School, University of Texas Health Science Center at Houston, TX 77030, USA

关键词: hemophilia;    autoimmunity;    FVIII;    B cells;   

DOI  :  10.3390/antib3020192

来源: mdpi

【 摘 要 】

Immune responses directed against clotting factor FVIII (FVIII) seriously complicate treatments for patients with hemophilia A. This response can manifest in congenital hemophilia A patients who generate inhibitor antibodies that bind and inactivate “transplanted” replacement FVIII, as well as in acquired hemophiliacs, whose immune systems have lost tolerance to self-FVIII. Regardless of the mechanism by which production of anti-FVIII inhibitor antibody is triggered, the maintenance of this deleterious response in both congenital and acquired hemophiliacs likely relies upon FVIII specific memory B cells. In this review, the similarities and differences in the kinetics, specificities, and subclasses of antibodies produced in response to allo- and auto-FVIII is outlined. A brief description of the immune cell interactions that contribute to maintenance of antibody response, focusing on development of memory B cells and/or long lived plasma cells is also presented. As current treatments for inhibitor antibodies are not successful in all patients, a better understanding of the functions and persistence of memory B cells specific for FVIII is required. Herein, both clinical and experimental data regarding the effects of immune tolerance induction on memory B cell subpopulations is discussed. Finally, the outcomes of B cell-specific depletion via rituximab in hemophilia and other autoimmune diseases are discussed to highlight insights into the subpopulations of memory B cells that contribute to the development and maintenance of successful tolerance to FVIII.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.