Fc receptor blockade and immune thrombocytopenic purpura.
Inhibition of antibody-coated platelet destruction in patients with immune thrombocytopenic purpura (ITP) is a well-known mechanism of treatment effect. A number of interventions that would ameliorate the thrombocytopenic effect of ITP patient plasma when infused into normal recipients were demonstrated in 1965. Subsequently, the antibody-coated chromium-labeled red blood cell clearance study was developed to allow direct in vivo assessment of Fc receptor (FcR) blockade. This was first demonstrated for corticosteroids but more extensive investigation began with the study of intravenous infusions of gammaglobulin (IVIg). The unequivocal demonstration of FcR blockade following IVIg Initiated novel approaches. One involved the infusion of a monoclonal anti-FcRIII ligand-blocking antibody into patients with refractory ITP. The efficacy of this treatment demonstrated that FcR blockade was not an epiphenomenon but rather an important mechanism of the increase in the platelet count in patients with ITP. Confirmation of its importance was obtained from the infusion of intravenous (IV) anti-D and the use of the isolated Fc piece of IgG. Recent studies have begun to explore the possibility of a monoclonal anti-FcRI and monoclonal anti-Ds. In summary, FcR blockade is an important mechanism of treatment effect in patients with ITP. Cytokine release as a consequence of this interaction and other immunomodulatory effects have only begun to be studied.
Bussel
J B
JB
Department of Pediatrics, New York Hospital, New York 10021, USA.
D000305:Adrenal Cortex Hormones / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000276:immunology / Q000627:therapeutic use; D010587:Phagocytosis / Q000187:drug effects; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000188:drug therapy* / Q000276:immunology; D011961:Receptors, Fc / Q000037:antagonists & inhibitors*
D000305:Adrenal Cortex Hormones; D016756:Immunoglobulins, Intravenous; D011961:Receptors, Fc