Alloantibody IgG subclasses have differential activity in clearing transfused platelets in mice

ABSTRACT: Platelet transfusion is a necessary life-sustaining therapy for extreme thrombocytopenia from multiple etiologies. However, refractoriness develops in some patients such that transfused platelets are rapidly cleared and refractory patients are at risk for catastrophic hemorrhage. One cause of refractoriness is humoral immunization to major histocompatibility complex I (MHC-I) alloantigens. However, ∼50% of patients with alloantibodies to MHC-I do not become refractory. The factors that determine whether an alloimmunized patient is refractory remain undefined. Both mice and humans encode 4 distinct immunoglobulin G (IgG) subclasses, each with different effector function characteristics. In this article, we forward the hypothesis that IgG subclass composition of alloantisera affects refractoriness. A novel panel of mice was generated with mutated effector function for different murine IgG subclasses. Elimination of effector function of IgG2c (but not IgG1 or IgG2b) eliminated the ability of alloantisera to clear transfused platelets. Together, these data demonstrate the differential platelet-clearing activity of distinct IgG subclasses in vivo and support the hypothesis that differences in IgG subclass affect whether alloimmunization results in refractoriness to platelet transfusion.