RBC hemolysis and cellular effector mechanisms (RHANCEM)

The diagnosis of humoral (antibody)-mediated immune hemolysis relies on a positive direct antiglobulin test (DAT), be it in cases of autoimmune hemolytic anemias (AIHAs) or alloimmune-mediated acute or delayed hemolytic transfusion reactions (HTRs; DHTRs), and/or a positive indirect antiglobulin test (IAT) due to re-activating alloantibodies against transfused red blood cell (RBC) after prior sensitizations. These serologic signatures are readily ascertained by historic methods which are still used in blood banks and transfusion services today. However, in some cases with acquired hemolysis, no antibodies are found, and alternative mechanisms are lacking; 5-10% of AIHA lack apparent drivers. In other cases, the transfusion of appropriate donor blood may fail to achieve the expected rise in hemoglobin and instead culminate in hemolysis without apparent cause. The problem to be addressed in this proposal is the hitherto unidentified mechanism of RBC hemolysis in seronegative patients. These patients represent an unresolved diagnostic challenge. Progress has stalled in the search for a reliable alternative diagnostic test. The immediate goal of this research is to identify specific white blood cell subsets responsible for antibody-independent hemolysis. The long-term goal is the development of a simple cell-based assay of cell-mediated hemolysis to pinpoint the mechanism(s) in seronegative cases, and pathway-minded therapeutic opportunities.

BRANCH, Donald

Canadian Blood Services

Intramural Research Grant Program

Ontario

$399,927