In which rheumatic diseases is IVIG indicated? How might it work in these diseases?
• Autoimmune thrombocytopenia: Fc portion of IVIG binds the Fc receptor on reticuloendothelial cells blocking the removal of antibody-coated cells.
• Kawasaki disease: IVIG reduces expression of adhesion molecules on endothelial cells, binds cytokines that cause inflammation, reduces number of activated T cells, and binds staphylococcal toxin superantigens.
• Dermatomyositis and polymyositis: the Fc portion of IVIG can bind to C3b and C4b, decreasing complement activation.
• Autoimmune hemolytic anemia and neutropenia (off-label).
Other proposed mechanisms that may explain IVIG effectiveness in autoimmune diseases include:
• Antiidiotypic antibodies bind surface immunoglobulin on B cells preventing binding to target autoantigen.
• Saturation of neonatal Fc receptor resulting in accelerated degradation of pathogenic IgG.
• Sialylated fraction of IVIG (5% of total IVIG) binds to the protein, DC-SIGN, on dendritic cells resulting in enhanced expression of inhibitory FcγRs (FcγRIIb) on effector macrophages which can attenuate inflammation.
• Others: enhancement of Treg function, inhibition of dendritic cells.