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Papers by Sergio Spalter
Clinical and Experimental Immunology, May 1, 1996
Intravenous immune globulin (IVIG) exhibits a nmnber ofimmunomodulatory properties that are media... more Intravenous immune globulin (IVIG) exhibits a nmnber ofimmunomodulatory properties that are mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations. Five predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in immune-mediated diseases: (i) functional blockade of Fe receptors on splenic macrophages: (ii) inhibition of complement-mediated damage, an effect that is dependent on the ability of lgG to bind C3b and C4b and thus reduce the number of activated complement fragments that may deposit on target surfaces of complement activation: (iii) modulation of the production of cytokines and cytokine antagonists: (iv) neutralization of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG, a mechanism that accounts for the rapid decrease in titre of circulating autoantibodies that is often observed within hours following the infusion of IVIG: (v) selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half-life of the infused immunoglobulin and that is directly relevant to the ability of IVIG to, for example, suppress autoantibody-producing clones in patients with antibody-mediated autoimmune disease and modulate graft rersus host disease (GVHD). IVIG has been shown to downrcgulate or activate B-ccll clones expressing surface lgG that is complementary (anti-idiotypic) to V regions of antibodies present in IVIG. IVIG has been shown also to interact with surface molecules ofT cells that arc essential to immune regulation, such as the ofi TCR, CDS, CD4, non-polymorphic determinants of MHC class I molecules and adhesion molecules ofT and B cells. The complex interactions of IVIG with functional molecules of cells of the immune system arc relevant to its therapeutic effects in T cell-as well as B cellmediated diseases and indeed, to our understanding of the physiological role of normal IgG and antibody networks in controlling autorcactivity in healthy individuals.
Idiotypes in Medicine: Autoimmunity, Infection and Cancer, 1997
... NORMAL POLYSPECIFIC HUMAN IgG (INTRAVENOUS IMMUNOGLOBULIN, IVIg) Sergio H Spalter, Srini Kave... more ... NORMAL POLYSPECIFIC HUMAN IgG (INTRAVENOUS IMMUNOGLOBULIN, IVIg) Sergio H Spalter, Srini Kaveri and Michel D Kazatchkine ... Phase Autoantibodies Disease References Anti-fibrinogen autoimmune disease Myasthenia gravis SLE Ruiz-Arguelles, 1988 Dwyer et ...
Journal of Allergy and Clinical Immunology, 2002
Blood, 1999
It is widely accepted that the serum of healthy individuals contains natural antibodies only agai... more It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual’s red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that IgM and IgG antibodies reactive with autologous blood group antigens are present in the immunoglobulin fraction of normal human serum. Natural IgG anti-A antibodies purified by affinity chromatography from IgG of individuals of blood group A exhibited an affinity for A trisaccharide antigen in the micromolar range and agglutinated A red cells at sixfold higher concentrations than those required for agglutination with affinity-purified anti-A IgG of individuals of blood group B. Whereas autoantibodies reactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result of complementary intera...
Clinical and Experimental Immunology, May 1, 1996
Intravenous immune globulin (IVIG) exhibits a nmnber ofimmunomodulatory properties that are media... more Intravenous immune globulin (IVIG) exhibits a nmnber ofimmunomodulatory properties that are mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations. Five predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in immune-mediated diseases: (i) functional blockade of Fe receptors on splenic macrophages: (ii) inhibition of complement-mediated damage, an effect that is dependent on the ability of lgG to bind C3b and C4b and thus reduce the number of activated complement fragments that may deposit on target surfaces of complement activation: (iii) modulation of the production of cytokines and cytokine antagonists: (iv) neutralization of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG, a mechanism that accounts for the rapid decrease in titre of circulating autoantibodies that is often observed within hours following the infusion of IVIG: (v) selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half-life of the infused immunoglobulin and that is directly relevant to the ability of IVIG to, for example, suppress autoantibody-producing clones in patients with antibody-mediated autoimmune disease and modulate graft rersus host disease (GVHD). IVIG has been shown to downrcgulate or activate B-ccll clones expressing surface lgG that is complementary (anti-idiotypic) to V regions of antibodies present in IVIG. IVIG has been shown also to interact with surface molecules ofT cells that arc essential to immune regulation, such as the ofi TCR, CDS, CD4, non-polymorphic determinants of MHC class I molecules and adhesion molecules ofT and B cells. The complex interactions of IVIG with functional molecules of cells of the immune system arc relevant to its therapeutic effects in T cell-as well as B cellmediated diseases and indeed, to our understanding of the physiological role of normal IgG and antibody networks in controlling autorcactivity in healthy individuals.
Idiotypes in Medicine: Autoimmunity, Infection and Cancer, 1997
... NORMAL POLYSPECIFIC HUMAN IgG (INTRAVENOUS IMMUNOGLOBULIN, IVIg) Sergio H Spalter, Srini Kave... more ... NORMAL POLYSPECIFIC HUMAN IgG (INTRAVENOUS IMMUNOGLOBULIN, IVIg) Sergio H Spalter, Srini Kaveri and Michel D Kazatchkine ... Phase Autoantibodies Disease References Anti-fibrinogen autoimmune disease Myasthenia gravis SLE Ruiz-Arguelles, 1988 Dwyer et ...
Journal of Allergy and Clinical Immunology, 2002
Blood, 1999
It is widely accepted that the serum of healthy individuals contains natural antibodies only agai... more It is widely accepted that the serum of healthy individuals contains natural antibodies only against those blood group A or B antigens that are not expressed on the individual’s red blood cells. The mechanisms involved in tolerance to autologous blood group antigens remain unclear. In the present study, we show that IgM and IgG antibodies reactive with autologous blood group antigens are present in the immunoglobulin fraction of normal human serum. Natural IgG anti-A antibodies purified by affinity chromatography from IgG of individuals of blood group A exhibited an affinity for A trisaccharide antigen in the micromolar range and agglutinated A red cells at sixfold higher concentrations than those required for agglutination with affinity-purified anti-A IgG of individuals of blood group B. Whereas autoantibodies reactive with self A and B antigens are readily detected in purified IgG and IgM fractions, their expression is restricted in whole serum as a result of complementary intera...