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

Treatment of acute immune thrombocytopenic purpura (ITP) with intraven ous 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); p latelets sensitised by IgG could not be cleared by cells of the reticu loendothelial system if FcgammaR on these cells was blocked with IVIG. To find out whether this putative mechanism is correct, we treated tw elve children who had acute ITP with intravenous infusions of Fcgamma fragments. Eleven children showed rapid increases in platelet counts t o above the critical value of 50 x 10(9)/L, thereby avoiding major hae morrhagic risk. The response was stable in six patients and transient in five. No adverse reactions were observed. In responders who had det ectable platelet-associated IgG before treatment (> 1500 IgG per plate let), platelet IgG fell substantially with treatment. Serum soluble CD 16 (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 tr eatment of acute ITP in children. The efficacy of Fcgamma fragments st rengthens the hypothesis that FcgammaR blockade is the main mechanism of action of IVIG in ITP, although other immunoregulatory mechanisms t riggered by the presence of increased sCD16 concentrations in serum co uld be involved in the clinical benefit observed.