Infusion of Fcγ fragments for treatment of children with acute immune thrombocytopenic purpura

• Published in: The Lancet (British edition) Vol. 342; no. 8877; pp. 945 - 949
• Main Authors: Debré, M, Griscelli, C, Bonnet, M-C, Carosella, E, Philippe, N, Reinert, P, Vilmer, E, Kaplan, C, Fridman, W.H, Teillaud, J-L
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 16.10.1993; Lancet
• Subjects: Adolescent; Biological and medical sciences; Blood Platelets - drug effects; Child; Child, Preschool; Chromatography, High Pressure Liquid; Female; Hematologic and hematopoietic diseases; Humans; Immunoglobulin Fc Fragments - administration & dosage; Immunoglobulin Fc Fragments - urine; Infusions, Intravenous; Male; Medical sciences; Platelet diseases and coagulopathies; Purpura, Thrombocytopenic - drug therapy; Receptors, IgG - drug effects; Human; Immunopathology; Immunoglobulins; Treatment; Intravenous administration; Fc-Fragment; Immunotherapy; Idiopathic; Hemopathy; Child
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/0140-6736(93)92000-J

Summary 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 Fcγ receptor (FcγR); platelets sensitised by IgG could not be cleared by cells of the reticuloendothelial system if FcγR 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 Fcγ fragments. Eleven children showed rapid increases in platelet counts to above the critical value of 50 × 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 sFcγRIII) concentrations, measured in five children, showed transient or stable increases that correlated with the rise in platelet count. No sCD16 was detected in the Fcγ preparation used. We conclude that the infusion of Fcγ fragments is an efficient treatment of acute ITP in children. The efficacy of Fcγ fragments strengthens the hypothesis that FcγR 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.