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Semin Hematol. 1992 Jul;29(3 Suppl 2):72-82.

Role of intravenous immunoglobulin G in autoimmune hematologic disorders.

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Division of Hematology, Hospital for Sick Children, Toronto, Ontario, Canada.


The data presented in this review established IVIG therapy as an important treatment modality in the autoantibody-mediated cytopenias and coagulation disorders of both children and adults. The immediate response to therapy is thought to be related to nonspecific Fc-receptor blockade of mononuclear phagocytes in the reticuloendothelial system (autoimmune cytopenias), or to idiotypic antibody interaction with pathologic autoantibodies (in acquired coagulation disorders). Although less frequent, long-term responses to IVIG therapy are reported. Such responses must involve an immunomodulating effect of IgG that influences T- and B-cell function, with inhibition of pathologic autoantibody formation. It is possible that idiotypic antibody interactions play a part in long-term responses. The experience with IVIG therapy in the decade following Imbach's important observations reported in 1981 has provided a sound data base regarding the use of this important therapy in patients with autoimmune hematologic disorders. The challenge of the next decade should be to further investigate mechanisms of action of this important therapy and to conduct carefully controlled studies to answer specific clinical questions. Examples of such questions include the following: (1) Can IVIG therapy, administered early in the course of illness in selected children with acute ITP, decrease the incidence of chronic ITP?; (2) Is maintenance, high-dose IVIG therapy a cost-effective method for the management of patients with chronic ITP refractory to corticosteroid therapy and splenectomy?; and (3) Can IVIG therapy administered to selected pregnant women with ITP significantly reduce the incidence of serious thrombocytopenia in their offspring? In conducting these studies, consideration should be given to the type of IVIG preparation used and to the treatment protocol implemented. It is evident that responses to unmodified IgG preparations (with the Fc-receptor part of the molecule left largely intact) are superior to preparations that have been modified during preparation. Responses are also likely to be dose-related. The data reported for IVIG therapy in patients with acquired factor VIII deficiency suggests that the idiotypic antibody content of IgG preparations is also of importance; if so, preparations selected from specific donor pools (for example, multiparous women) known to contain higher levels of circulating autoantibodies (than those from primiparous women or untransfused males) may provide a degree of benefit not seen with standard IVIG preparations. It is therefore important that clinicians and laboratory specialists work closely together in the design and conduct of future clinical trials initiated to answer those important clinical questions raised by the first decade of observations with IVIG therapy for autoimmune hematologic disorders.

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