Effect of commercial immunoglobulin G preparation on human monocyte Fc‐receptor dependent binding of antibody coated platelets

Abstract

This study examined the in vitro effect of a commercial immunoglobulin preparation on human monocytes and the Fc-receptor dependent binding of antibody coated platelets. Monocytes were exposed to Sandoglobulin in vitro and subsequently examined for membrane surface bound IgG. Dramatic increments of surface IgG were found which were maximal with 18 h exposure and somewhat higher at 4 degrees C than 37 degrees C. Ultracentrifugations of Sandoglobulin immediately prior to monocyte exposure reduced the monocyte membrane IgG by 75%. The 18 h exposure at 37 degrees C produced dramatic impairment of monocyte Fc-receptor binding of IgG coated platelets (P less than 0.001) while exposure for 18 h at 4 degrees C produced a modest impairment of Fc-receptor function. These studies indicate that Sandoglobulin contains IgG aggregates which are able to firmly bind to the monocyte surface in a time and temperature dependent fashion. The dramatic impairment of Fc-receptor function at 37 degrees C and not at 4 degrees C suggests that Fc-receptor modulation, as well as competitive inhibition/steric hindrance, contribute to impairment of monocyte Fc-receptor function.

In vitro effects of gammaglobulin (IgG) on human monocyte Fc receptor function. I. Effect on monocyte membrane‐associated IgG and Fc receptor‐dependent binding of antibody‐coated platelets

“…Other potential mechanisms whereby immune globulin infusions produce improved platelet counts , presumably through improved platelet survival, need additional study, including alteration in antiplatelet antibody synthesis via antiidiotype suppression or other mechanisms [20]. The observation in this report that simple Millipore filtration is able to remove the minor IgG fraction that has binding affinity for Fc receptors may, in fact, be a useful technique for determining the role of the IgG monomers in the therapeutic efficacy of IgG infusions.…”

Plasmapheresis combined with interferon: An effective therapy for multiple sclerosis

“…The immunomodulating agents administered in conjunction with PP were used to alter T lymphocyte expansion (cyclophosphamide) [37], to diminish lymphocyte expansion, cerebrospinal fluid immunoglobulin synthesis, and production of arachidonic acid metabolites (methylprednisolone) [38], and to block Fc-dependent binding of antibody-coated cells (immunoglobulin) [39,40]. Though it is not possible to sort out the effects of these drugs on the course of MS or on the various immunologic studies presented, we feel that PP played a role in the improvement of our MS patients.…”

Intravenous immunoglobulin therapy in systemic lupus erythematosus‐associated thrombocytopenia

“…In vitro studies demonstrate that monomeric IgG also binds to macrophage Fc receptors, leading to internalization and loss of surface expression of Fc receptors (15). Saleh et a1 (18) have shown that therapeutic gamma globulin preparations can impair human monocyte Fc receptor binding of IgG-coated platelets in vitro. Kimberly et a1 (17) have shown that IV immunoglobulin therapy decreases the monocyte-binding affinity of IgG aggregates without decreasing the number of available binding sites (17).…”

“…The mechanism of action of IV immunoglobulin in these disorders, which is best studied in ITP, has been attributed to down-regulating autoantibody production (7.9.14. IS) and/or delaying the Fc receptormediated clearance of antibody-coated platelets by the mononuclear phagocyte system (15)(16)(17)(18). Because of the widely reported success of IV immunoglobulin in the treatment of ITP, we studied its effects on the clinical and immunologic status of patients with SLEassociated thrombocytopenia.…”