According to the National Hemophilia Foundation, Hemophilia A, also called factor VIII (FVIII) deficiency or classic haemophilia (lat. hemophilia), is a genetic disorder caused by missing or defective factor VIII, a clotting protein. Although it is passed down from parents to children, about 1/3 of cases are caused by a spontaneous mutation, a change in a gene. However, the scientific team at the Emory University School of Medicine has made an important discovery that could potentially change the way doctors understand and treat inhibitor development in haemophilia A. They found that MZ B cells play a critical role in initiating FVIII inhibitor formation and suggest a potential strategy to prevent anti-FVIII alloantibody formation in patients with haemophilia A.
Sean R. Stowell, MD, PhD, from the Center for Transfusion Medicine and Cellular Therapies at the Department of Pathology and Laboratory Medicine at Emory University School of Medicine in Atlanta, Georgia, led this research. Researchers mentioned that although factor VIII (FVIII) replacement therapy can be lifesaving for patients with hemophilia A, neutralizing alloantibodies to FVIII, develop in a significant number of patients and actively block FVIII activity, making bleeding difficult to control and prevent.
The study found that, in mice, marginal zone B-cells did respond to factor VIII. Marginal zone (MZ) B-cells are primarily found in the spleen, where they serve a vital role in the development of immunity. These cells are involved in the body’s process of identifying and reacting to external antigens in the blood. By demonstrating that MZ B-cells react to factor VIII, researchers have potentially revealed more about how the body forms inhibitors in response to factor VIII treatment.
It was also found that by removing MZ B-cells in mice with a genetic factor VIII deficiency they could prevent the formation of inhibitors entirely. However, the authors warned that this process would present a more serious risk in humans. The importance of MZ B-cells and their widespread presence within the body would mean that their total depletion would leave a patient open to a much greater risk of infection.