INFUSION OF FC-GAMMA-FRAGMENTS FOR TREATMENT OF CHILDREN WITH ACUTE IMMUNE THROMBOCYTOPENIC PURPURA

Treatment of acute immune thrombocytopenic purpura (ITP) with intravenous immunoglobulin (IVIG) induces partial or complete responses, shown by transient or persistent increases in platelet count. The clinical benefit could be due to blockade of the Fcgamma receptor (FcgammaR); platelets sensitised by IgG could not be cleared by cells of the reticuloendothelial system if FcgammaR on these cells was blocked with IVIG. To find out whether this putative mechanism is correct, we treated twelve children who had acute ITP with intravenous infusions of Fcgamma fragments. Eleven children showed rapid increases in platelet counts to above the critical value of 50 x 10(9)/L, thereby avoiding major haemorrhagic risk. The response was stable in six patients and transient in five. No adverse reactions were observed. In responders who had detectable platelet-associated IgG before treatment (> 1500 IgG per platelet), platelet IgG fell substantially with treatment. Serum soluble CD16 (sCD16 or sFcgammaRIII) concentrations, measured in five children, showed transient or stable increases that correlated with the rise in platelet count. No sCD16 was detected in the Fcgamma preparation used. We conclude that the infusion of Fcgamma fragments is an efficient treatment of acute ITP in children. The efficacy of Fcgamma fragments strengthens the hypothesis that FcgammaR blockade is the main mechanism of action of IVIG in ITP, although other immunoregulatory mechanisms triggered by the presence of increased sCD16 concentrations in serum could be involved in the clinical benefit observed.