Anti-idiotype interactions are not required for the protective effect of intravenous immunoglobulin in a murine model of passively transferred immune thrombocytopenia

Abstract

The use of intravenous immunoglobulin (IVIg) as a treatment for autoimmune disease was first realized in the reversal of thrombocytopenia in Immune Thrombocytopenic Purpura (ITP) and, based upon this finding, it is currently used to treat an increasing number of autoimmune states and to prevent graft rejection. Previous reports, as well as much recent literature, have implied that the reactivity of variable region-reactive (anti-idiotypic) antibodies predominantly accounts for the beneficial effects of IVIg. Anti-idiotypic antibodies reactive with endogenous Ig, autoantibodies, and those anti-idiotype antibodies that modulate immune function have been implicated. Herein, we demonstrate that IVIg ameliorates thrombocytopenia in a passively transferred model of ITP (P-ITP) and that anti-idiotype antibodies present in IVIg ameliorates thrombocytopenia in a passively transferred model of ITP (P-ITP) and that anti-idiotype antibodies present in IVIg are not required for its protective effect. Both IVIg and an anti-idiotype-depleted IVIg protected equally against thrombocytopenia. As well, immunocompromised (SCID) mice, which lack endogenous IgM/G/A/D necessary for any idiotype-anti–idiotype interactions, were protected by IVIg against thrombocytopenia to the same degree as normal mice.