Life‐threatening hemolytic anemia due to an autoanti‐Pr cold agglutinin: evidence that glycophorin A antibodies may induce lipid bilayer exposure and cation permeability independent of agglutination

Abstract

The anti-Pr CA and rabbit anti-human GPA increased exposure of PE and increased membrane Ca(2+) permeability that may have caused hemolysis. The difference in the responses to these antibodies to enzyme treatment of RBCs suggests that they react with different epitopes on GPA.

IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI

“…Furthermore, our results exclude a role for ADCC and antibody-induced eryptosis as a possible cause of the RBC destruction in our patient, although such mechanisms have recently been proposed for the development of anemia associated with different types of anti-RBC antibodies. 22,29 The lack of in vitro erythrophagocytosis is consistent with the histologic finding of few signs of erythrophagocytosis in the spleen. Instead, we observed a RBC sequestration due to the marked accumulation of agglutinated RBCs in the spleen.…”

Lyse or not to lyse: Clinical significance of red blood cell autoantibodies

“…As described above, some autoantibodies directed to GPA can induce Ca-influx by aggregation of GPAs, leading to RBC destruction [53][54][55]. This mechanism might not be unique for anti-GPA antibodies, since anti-A IgG was also seen to induce RBC death by activation of cation channels leading to Ca entry and subsequent loss of membrane integrity [67].…”

“…This specificity has been seen often with much higher degree of hemolysis than the antibody quantity would predict [52]. This was shown to be caused by a recently discovered mechanism of RBC destruction, namely GPA aggregation by the antibody leading to membrane destabilization and subsequent calcium influx [53][54][55][56].…”

Brown Recluse Spider Bite Mediated Hemolysis: Clinical Features, a Possible Role for Complement Inhibitor Therapy, and Reduced RBC Surface Glycophorin A as a Potential Biomarker of Venom Exposure

“…Support for this theory comes from the observation that some patients with BRSB mediated hemolysis demonstrate IgG deposition on their red cells in vivo (positive DAT) [9]. Moreover, cases of severe autoimmune hemolytic anemia with a similar clinical presentation as BRSB mediated hemolysis are known to be caused by autoantibodies directed against minor blood group antigens associated with glycophorin A [30,34,35]. However, we believe that the fact that BRSB mediated hemolysis can be modeled in vitro rules out an active immune component (such as autoantibody formation) to the hemolysis.…”