Immune thrombocytopenia and Fc receptor-mediated phagocyte function

Abstract

The response to intravenous immunoglobulin treatment (IVIG) is thought, in part, to be due to blockade of Fc receptor for IgG in the mononuclear phagocyte system (MPS). We have studied this by measuring splenic clearance of heat-damaged and IgG antibody-coated red cells in immune thrombocytopenic patients receiving IVIG. Clearance of heat-damaged red blood cells (HDRBC) labelled with technetium 99MM was measured in eight patients before and after a 5-day infusion of IVIG. In six of the eight there was an enhanced clearance of HDRBC post IVIG. Clearance studies were performed in eight rhesus-D-positive patients using autologous red cells coated with anti-D and labelled with 99MTc. The time taken for the radioactivity at 3 min to fall to 50% (T1/2) was calculated. The T1/2 increased in seven of the eight patients from a mean of 78.5 min to 137.1 min, a prolongation of 74.6%. In addition, we have examined the effect of IVIG on Fc-mediated phagocytosis by neutrophils. Platelet phagocytosis by patients' neutrophils was measured using opsonized autologous platelets in nine patients. There was a marked reduction in platelet phagocytosis as measured by formazan production in all patients at day 4-5 when compared with the preinfusion value, and in half of these this reduction was still evident at further studies, 1 week after the end of the infusion period. The platelet count rose in parallel with the fall in platelet phagocytic ability of the neutrophils, reaching a peak at 7 days post infusion, and fell with the recovery of phagocytic function in weeks 2 and 3. These findings suggest that IVIG has a marked effect on Fc-mediated phagocytosis.