Intravenous immunoglobulins induce potentially synergistic immunomodulations in autoimmune disorders

The increase in platelets in patients with immune thrombocytopenia (ITP) by intravenous administration of human immunoglobulin concentrates (IVIG) reflects a therapeutic immunomodulatory intervention targeted at the disturbed immune response in many inflammatory and autoimmune disorders. These immunoglobulin concentrates contain large numbers of antibodies as well as trace levels of various other immunologically active molecules. Clinical and laboratory studies have documented various mechanisms of action of IVIG. The complex network of immunological reactions resulting from the infusion of IVIG includes changes in several cytokines, interactions with dendritic cells, T- and B- lymphocyte effects, macrophage effects, mediated by distinct Fc-gamma receptors. In addition, effects on complement components and apoptosis have also been observed. Synergism between the different elements of the immune response characterizes the beneficial effects of IVIG in inflammatory and autoimmune disorders. They have immunopathogeneses and clinical manifestations which are difficult to define and therefore IVIG treatment indications remain heterogeneous. Dose finding studies are missing for most of the indications of the drug. In future research, defining the appropriate subgroups of patients should be undertaken. This may be accomplished by prospective registries collecting data on large numbers of patients with long-term follow-up. Controlled clinical and laboratory studies may follow based on new, validated patient selection criteria and focused on mechanisms of action, leading to more evidence-based indications.