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.
- • Chronic inflammatory demyelinating polyneuropathy.
- • Antiphospholipid antibody syndrome (off-label).
- • 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.
