Red Blood Cell masquerade: polymer-mediated immunocamouflage provides Rh D antigen-safe blood


By Solmaz Sobhanifar, Postdoctoral Fellow in the Natalie Strynadka Lab

Although the existence of ABO blood group antigens is common knowledge, it is less widely known that red blood cells (RBCs) can express more than 300 other antigens belonging to 35 blood group systems. As such, RBCs demonstrate extraordinary immunogenic complexity that varies among individuals and ethnicities.

The Rh blood groups were discovered 40 years after the ABO blood groups, and named aftesolmaz postr the rhesus monkey, first used in making antiserum for sample blood typing. Among 50 known Rh antigens, the Rh D antigen is the most immunogenically and clinically problematic, second only to ABO blood group antigens. As a result, the D antigen poses a significant risk of acute immune response in blood transfusions from D+ donors to D- recipients. This risk is furthermore exacerbated in countries, such as China, where Rh D- blood is rare, resulting in an inadequate inventory.

In a recent article in the American Journal of Hematology, Li Li, a postdoctoral fellow from Mark Scott’s lab at the CBR, along with her colleagues developed a technique for camouflaging Rh D+ RBCs to avoid acute anti-D transfusion reactions. Using this method, antigens are masked by the attachment of immunologically inert polymers such as mPEG (methoxypolyethylene glycol) to the surface RBC membrane in a process that preserves cell morphology, structure and function. The polymers physically hinder the binding of problematic antibodies and avoid clearance of the Rh D+ red blood cells by macrophages.

Dr. Mark Scott

Dr. Mark Scott

Li and colleagues assessed the success of mPEG chain length and grafting concentration on disguising the Rh D+ antigen by measuring antibody binding and immune-mediated destruction of RBCs. This allowed the authors to identify important engineering parameters, resulting in excellent immunocamouflage of D antigens and a clinically significant level of protection. These findings serve as a proof-of-concept demonstrating the ability to use membrane-attached polymer chains as a safe and effective means of providing “D-safe” blood to recipients in areas where D- blood is unavailable.