Intravenous immunoglobulins in autoimmune cytopenias: an old tool with an alternative dosing schedule

Abstract

Introduction
Intravenous immunoglobulins (IVIG) have been used in the last 40 years for the treatment of various autoimmune disorders, including neurologic and hematologic diseases¹. Their mechanism of action is pleiotropic and not yet fully understood. IVIG saturate Fc receptors (FcR) on spleen macrophages, inhibiting phagocytosis and antibody-dependent cell-mediated cytotoxicity, in particular, in antibody-mediated autoimmune cytopenias (AIC) such as immune thrombocytopenia (ITP). Moreover, IVIG increase autoantibody clearance by blocking neonatal FcR (FcRn), a natural mechanism that protects circulating antibodies from lysosomal degradation. In addition, anti-idiotype antibodies in IVIG preparations may interact with variable regions of natural or disease-associated autoantibodies, promoting their clearance. Finally, inhibition of complement-mediated damage and modulation of inflammatory cytokine patterns have been proposed as additional mechanisms². IVIG are a well-recognized tool for rapidly increasing the platelet count and reducing bleeding in ITP during the acute phase. Although response rates are over 80%, they are generally of a short duration³. IVIG are less efficacious in autoimmune hemolytic anemia (AIHA); a 1993 study reported a pooled response rate of around 40%⁴, while more recent retrospective evidence suggests a response to IVIG in severe AIHA flare ups comparable to that obtained with steroids alone in non-severe events⁵.