Immunomodulation of autoimmune diseases by high-dose intravenous immunoglobulins

IVIg therapy in autoimmunity and related disorders: our experience with a large cohort of patients

“…Several mechanisms have been proposed by different groups to explain the effects of IVIg therapy [1,3,[25][26][27] and include enhanced suppressor activity with reduction of the secretion of proinflamatory cytokines and release of inhibitors; Fc receptor blockade; complement regulation by activating it and therefore diverting it from its target [28]; B-and T-cell regulation; idiotypenetwork regulation; enhanced clearance of IgG, inhibition of macrophage mediated phagocytosis; activity against autoantibodies like ANA, anti-dsDNA and aCL (it has been demonstrated that IVIg binds to idiotypes in the variable region of immunoglobulins) [29]); neutralization of superantigens [1]; and interference with dendritic cell differentiation probably abrogating the recognition that gives rise to the disease [30].…”

Intravenous immunoglobulins induce the in vitro differentiation of human B lymphocytes and the secretion of IgG

“…Although the origin of autoimmune diseases remains enigmatic, defects in immunoregulatory mechanisms are assumed to play a central role [3][4][5] and many authors consider that a failure in V-region connectivity is responsible for the emergence of pathologic autoantibodies. [6][7][8][9][10] Following treatment with IVIGs, the improvement in the patient's health is often characterized by a diminution of the level and activity of pathologic autoimmune antibodies. [11][12][13] Many mechanisms have been proposed to explain the beneficial effects of IVIGs but their exact mode of action remains unclear in most diseases.…”

“…26,27 Therefore, anti-idiotypic antibodies present in IVIGs have been proposed to restore homeostasis in patients with autoimmune diseases. 1,10,19,28 In fact, many autoimmune diseases are characterized by dominant idiotypes, present on pathologic IgG, 29 which are suitable targets for anti-idiotypes present in IVIGs. Finally, sera of patients in remission contained anti-idiotypic antibodies specific for autoantibodies and showed a decreased level of pathologic antibodies.…”

Interaction of high molecular weight kininogen binding proteins on endothelial cells

“…Intravenous immune globulin (IVIg) has broad therapeutic applications with beneficial effects in several autoimmune and inflammatory diseases, in particular in those associated with alterations of vascular endothelial functions (1,2). The endothelium, which exerts anti-thrombotic functions under physiological conditions, may indeed become a pro-thrombotic surface (3).…”