Synergizing host factors (including obesity-unadjusted dosing and existing inflammation) marked this severe post-IVIG hemolytic crisis. Group A antigen restriction to myeloid tissues, with H Secretor phenotype, may have contributed, rendering this bone marrow transplant chimera vulnerable to anti-A in a manner analogous to the idiosyncratic effect of therapeutic anti-D in certain D+ ITP recipients. However, MMA suggested a macrophage activation state as contributory, perhaps precipitated by existing inflammation.
BACKGROUNDWarm autoimmune hemolytic anemia (wAIHA) is a blood disorder characterized by the increased destruction of autologous red blood cells (RBCs) due to the presence of opsonizing pathogenic autoantibodies. Preliminary reports published more than three decades ago proposed the presence of two wAIHA subtypes: Type I, in which autoantibodies preferentially recognize the oldest, most dense RBCs; and Type II, characterized by autoantibodies that show no preference.STUDY DESIGN AND METHODSWe evaluated patients having wAIHA for Type I and II subtype using discontinuous Percoll gradient age fractionation and direct antiglobulin test (DAT). We performed Western immunoblotting and mass spectrometry to show autoantibody specificity for Band 3. We investigated Band 3 tyrosine phosphorylation in different Percoll fractions to determine aging associated with oxidative stress.RESULTSWe confirm the existence of two subtypes of wAIHA, Type I and Type II, and that autoantibodies recognize Band 3. Type I patients were characterized by five Percoll fractions, with a DAT showing IgG opsonization F1 < F5 and elevated Band 3 phosphorylation compared to healthy controls (HCs). In contrast, Type II wAIHA patients were characterized by three to four Percoll fractions, where the DAT IgG opsonization shows F1 ≥ F3/4 and Band 3 phosphorylation was absent or significantly decreased compared to HC.CONCLUSIONSType I patients have increased Band 3 tyrosine phosphorylation that may represent accelerated aging of their RBCs resulting in exacerbation of a pathologic form of RBC senescence. Type II patients show decreased Band 3 tyrosine phosphorylation and lack the oldest, most dense RBCs suggesting premature RBC clearance and a more severe wAIHA.
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