Role of natural antibodies in immune homeostasis: IVIg perspective.

Intravenous immunoglobulin (IVIg) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. Although a considerable progress has been made in understanding the mechanisms by which IVIg exerts immunomodulatory functions in these diseases, they remain not fully elucidated. The mode of action of IVIg is complex, involving interference with activation of complement and the cytokine network, modulation of: idiotype network, expression of Fc receptors, and activation, differentiation and effector functions of T and B cells and of antigen-presenting cells such as dendritic cells. The therapeutic effects of IVIg most likely reflect the functions of natural antibodies in maintaining immune homeostasis in healthy individuals.

Intravenous immunoglobulins in autoimmune and inflammatory diseases: a mechanistic perspective.

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulins (IVIg) have increasingly been used as immunomodulatory agents in autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic, probably involving Fc-dependent and/or F(ab')2-dependent nonexclusive mechanisms of action. IVIg broadly interacts with the different components of the immune system: cytokines, complement, Fc receptors, and several cell surface immunocompetent molecules. IVIg has also an impact on effector functions of immune cells. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg, and we pointed out the need for new strategies to overcome the predicted increasing worldwide shortage of IVIg.

Intravenous immunoglobulin in autoimmune and inflammatory diseases: more than mere transfer of antibodies.

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulin (IVIg) has increasingly been used as an immunomodulatory agent in immune thrombocytopenic purpura, autoimmune neuropathies, systemic lupus erythematosus, myasthenia gravis, Guillain-Barré syndrome, and Kawasaki disease. Although IVIg benefits have been reported in many autoimmune and systemic inflammatory diseases, its mechanisms of immunomodulation are not fully understood and probably involve Fc-dependent and/or F(ab')(2)-dependent mutually non-exclusive effects. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg.

[Use of intravenous polyclonal immunoglobulins in autoimmune and inflammatory disorders]. / Utilisation des immunoglobulines polyclonales intraveineuses dans les pathologies auto-immunes et inflammatoires.

Initially used for the treatment of immunodeficiencies, intravenous immunoglobulins (IVIg) have increasingly been used as immunomodulatory agent in autoimmune and inflammatory disorders. The mode of action of IVIg is enigmatic, probably involving Fc-dependent and/or F(ab')2-dependent non-exclusive mechanisms of action. IVIg broadly interacts with the different components of the immune system: cytokines, complement, Fc receptors and several cell surface immunocompetent molecules. IVIg also has an impact on effector functions of immune cells. These mechanisms of action of IVIg reflect the importance of natural antibodies in the maintenance of immune homeostasis. We discuss here the recent advances in the understanding of immunoregulatory effects of IVIg, and we pointed out the need of new strategies to overcome the predicted increasing worldwide shortage of IVIg.

Intravenous immunoglobulin in autoimmune disorders: an insight into the immunoregulatory mechanisms.

Intravenous immunoglobulin (IGIV) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases in addition to supportive therapy of immunodeficient patients. IGIV is beneficial in several diseases, including acute and chronic/relapsing diseases, autoimmune diseases and inflammatory disorders. Therapeutic efficacy of IGIV has also been established in a number of dermatologic diseases. Although a considerable progress has been made in understanding the mechanisms by which IGIV exerts immunomodulatory functions in autoimmune diseases, they remain not fully elucidated. The mode of action of IGIV is complex, involving modulation of expression and function of Fc receptors, interference with activation of complement and the cytokine network, modulation of idiotype network, regulation of cell growth, alteration of cellular adhesion process, and effects on the activation differentiation and effector functions of T and B cells and of antigen-presenting cells. The therapeutic effects of IGIV most likely reflect the functions of natural antibodies in maintaining immune homeostasis in healthy people. The ability of IGIV to interact through V regions with complementary V regions of antibodies and antigen receptors as well as with relevant soluble and surface molecules provides the basis for inducing the selection of immune repertoires. Since IGIV is frequently used to treat autoimmune and inflammatory diseases for which evidence of its efficacy is insufficiently documented, controlled trials, particularly of some neurologic and dermatologic diseases, are imperative.

Intravenous immunoglobulin and dendritic cells.

Intravenous immunoglobulin (IVIg) has increasingly been used for the treatment of autoimmune and systemic inflammatory diseases, and in supportive therapy of immunodeficient patients. Available clinical and experimental evidence suggests, however, that a wide spectrum of immune-mediated conditions could benefit from IVIg, including acute and chronic/relapsing diseases and autoimmune diseases mediated by pathogenic autoantibodies or by autoaggressive T-cells. Dendritic cells (DCs) are professional antigen-presenting cells and because of their capacity to stimulate naïve T-cells, they play a central role in the initiation of primary immune responses. Several immunomodulatory agents have been shown to inhibit DC activation. Recently, we examined the effects of IVIg on differentiation, maturation, and functions of DCs. We demonstrate that DCs are one of the targets for the immunomodulatory effects of IVIg.