Premium
Antibody specific for the glycophorin A complex mediates intravenous immune globulin–resistant anemia in a murine model
Author(s) -
Chen Xi,
Ghaffar Hasan,
Jen ChaoChing,
Lazarus Alan H.
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12300
Subject(s) - hemolysis , antibody , immunology , medicine , anemia , autoimmune hemolytic anemia , hemolytic anemia , immune system , fc receptor , complement system
Background Therapy for patients with autoimmune hemolytic anemia ( AHA ) remains a major challenge. Patients with glycophorin A ( GPA )‐specific immunoglobulin G antibodies can have severe hemolysis, which may occur by mechanisms independent from traditional macrophage‐dependent Fc γ receptor ( Fc γ R )‐mediated extravascular hemolysis. As intravenous immune globulin ( IVIG ) is known to display its beneficial effects in Fc γ R ‐mediated cytopenias, and IVIG responses in AHA are inconsistent at best, we sought to gain insight into the mechanism of anemia by a GPA complex–specific monoclonal antibody ( TER 119) in a mouse model of immune hemolytic anemia and evaluate the therapeutic effect of IVIG . Study Design and Methods The anemic effect of the TER 119 antibody was studied in vitro by incubation of mouse RBC with the antibody and in vivo by infusing the antibody into normal mice versus mice genetically deficient for the Fc receptor γ chain ( Fc γ), complement C 3, mice naturally deficient in complement C 5, and splenectomized mice. IVIG efficacy in anemia was determined by treating mice with an intensive IVIG dosing regimen. Results The TER 119‐mediated anemia was independent of classical Fc γ R ‐, C 3‐, and C 5‐dependent mechanisms, but occurred by a mechanism consistent with RBC agglutination. In accordance with agglutination, the presence of the spleen accelerated the anemia observed but anemia could still occur in splenectomized mice. IVIG did not significantly affect the induction of anemia by TER 119. Conclusion The mechanism of anemia induced by AHA ‐causing antibodies may be an important factor to consider in the response to therapy with IVIG .