Principle Areas of Study
Define the factors that regulate the development of alloantibodies to transfused and transplanted alloantigens
Individuals with a variety of hematopoietic diseases, ranging from sickle cell anemia to bone marrow failure secondary to chemotherapeutic treatment of neoplasia, often require repeat transfusions of various blood products. In addition, individuals who are deficient in clotting factors, such as factor VIII, also necessitate clotting factor replacement therapy, which can also result in infusion of recombinant blood constituents. In each of these settings, individuals are exposed to antigens that can induce an immune response against the blood product or clotting factor. This can limit the effectiveness of the intervention and/or reduce the availability of compatible blood products for future transfusions. Moreover, development of alloimmunization to these blood borne antigens can increase the rate of severe, if not fatal, immune reactions following subsequent exposure to blood products.
Given the negative consequences of alloantibody formation against blood products, our lab focuses on defining the key immune factors responsible for regulating antibody formation against various blood borne alloantigens. These studies incorporate a variety of animal models and clinical studies to mechanistically examine the cells and factors responsible for alloantibody development. It is our hope that understanding the immune factors responsible for alloimmunization in these various settings will provide an opportunity to identify key immunological targets that may be manipulated to prevent alloimmunization in high risk populations.
Lab members working in this area
Amanda Mener, Patty Zerra, Cliff Sullivan, Ashley Bennett
- Stowell SR, Henry KL, Smith NH, Hudson KE, Halerson GR, Park JC, Bennett AM, Girard-Pierce KR, Arthur CM, Bunting ST, Zimring JC, Hendrickson JE. Alloantibodies to a paternally derived RBC KEL antigen lead to hemolytic disease of the fetus/newborn in a murine model. Blood 2013 Aug 22;122(8):1494-504
- Stowell SR, Girard-Pierce KR, Smith NH, Henry KL, Arthur CM, Zimring JC, Hendrickson JE. Transfusion of murine red blood cells expressing the human KEL glycoprotein induces clinically significant alloantibodies. Transfusion 2014 Jan;54(1):179-89
- Stowell SR, Winkler AM, Maier CL, Arthur CM, Smith NH, Girard-Pierce KR, Cumming RD, Zimring JC, Hendrickson JE. Initiation and regulation of complement during hemolytic transfusion reactions. Clin Dev Immunol 2012:307093