Blocking
FcγRI
and
FcγRIII
reduces
RBC
phagocytosis induced by patient‐derived anti‐E and anti‐K
Yaima Tundidor Cabado, Lazaro Gil Gonzalez, Yeniley Ruiz Noa, Alequis Pavon Oro, Akash Gupta, Yulia Lin, Heather VanderMeulen, Noah Zweig, Harley Meirovich, Amie Malkin, Chantal Armali, Katrina Billingsley, Donald R. Branch, Alan H. Lazarus Abstract
Introduction/Objectives
Red blood cell (RBC) alloantibodies can cause hemolytic transfusion reactions and complicate compatible blood provision. Although antibody‐opsonized RBCs are thought to be cleared partly through macrophage Fcγ receptor‐mediated phagocytosis, the Fcγ receptors involved in phagocytosis induced by non‐D alloantibodies remain incompletely defined.
Design and Methods
RBCs were sensitized with WHO anti‐E or anti‐C typing sera, or with plasma/serum from patients alloimmunized against RhE or K. Phagocytosis was assessed using THP‐1‐CD16A macrophages expressing FcγRI, FcγRIIA, and FcγRIII. Receptor involvement was evaluated using receptor‐specific deglycosylated blocking monoclonal antibodies.
Results
RBCs sensitized with WHO anti‐E or anti‐C sera, or with patient‐derived anti‐E or anti‐K alloantibodies, were phagocytosed by THP‐1‐CD16A macrophages. FcγRI or FcγRIII blockade reduced phagocytosis, although the magnitude of inhibition varied by antibody source and individual patient sample. FcγRIIA blockade produced little or no significant reduction across the conditions tested. Combined FcγRI and FcγRIII blockade produced the greatest inhibition with WHO reference sera, although inhibition was not fully additive. Patient‐derived anti‐E and anti‐K samples showed a similar pattern.
Conclusions
These findings support a functional contribution of FcγRI and FcγRIII to alloantibody‐mediated RBC phagocytosis in this in vitro macrophage model, while suggesting a limited role for FcγRIIA under these experimental conditions.