Summary
The efficacy of IgG infusion therapy in ITP is now established even in cases resistant to other forms of therapy. However, the mechanism of action is still speculative. We assume that a correction of the elevated thrombocyte clearance is brought about at several levels. First, antibodies specific for an inciting antigen (and for which the patient is deficient) may remove free antigen and/or immune complexes which adhere to platelet surfaces, thereby rendering platelets less susceptible to clearance. Second, IgG may act nonspecifically by protecting the platelet surface from becoming covered with immune complexes. Third, monomeric IgG may display a nonspecific inhibitory effect at the level of the interaction of immunologically altered platelets with Fc receptors of mononuclear phagocytes. For the latter effect, good in vivo evidence exists. However, it must be born in mind that interaction of antibodies with Fc receptors is but one mechanisms for triggering adherence and endocytosis. A variety of other receptors and binding sites exists which may interact with immunologically altered thrombocytes. These may either trigger phagocytes on their own or facilitate the interaction of antibodies and Fc receptors. How IgG infusion influences such interactions remains to be determinded.
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Abe T, Matsuda J, Kawasugi K, Yoshimura Y, Kinoshita T, Kazama M (1984) Clinical effect of intravenous immunoglobulin on chronic idiopathic thrombocytopenia purpura. Blut 47: 69
Bevilacqua MP, Amrani D, Mosesson MW, Bianco C (1981) Receptors for cold-insoluble globulin (plasma fibronectin) on human monocytes. J Exp Med 153: 42
Bianco C, Griffin FM, Jr., Silverstein SC (1975) Studies of the macrophage complement receptor. Alteration of receptor function upon macrophage activation. J Exp Med 141: 1278
Bussel JB, Kimberly RP, Schulman I, Cunningham-Rundles C, Cheung M, Smithwick E, O'Malley J, Barandun S, Hilgartner MW (1983) Intravenous gammaglobulin treatment of chronic idiopathic thrombocytopenic purpura. Blood 62: 480
Bussel JB, Schulman I, Hilgartner MW, Barandun S (1983) Use of intravenous gammaglobulin in the treatment of chronic immune thrombocytopenic purpura as a means to defer splenectomy. J Pediatr 103: 65
Carroll RR, Noyes WD, Kitchens CS (1983) High-dose intravenous immunoglobulin therapy in patients with immune thrombocytopenia purpura. JAMA 249: 1748
Cines DB, Schreiber AD (1979) Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets. N Engl J Med 300: 106
Czop JK, Austen KF (1982) Augmentation of phagocytosis by a specific fibronectin fragment that links particulate activators to the fibronectin adherence receptor of human monocytes. J Immunol 129: 2678
Czop JK, Fearon DT, Austen KF (1978) Opsonin-independed phagocytosis of activators of the alternative complement pathway by human monocytes. J Immunol 120: 1132
Dana N, Todd RF III, Pitt J, Springer TA, Arnaout MA (1983) Deficiency of a surface membrane glycoprotein (Mol) in man. J Clin Invest 73: 153
Ehlenberg AG, Nussenzweig V (1977) The role of membrane receptors for C3b and C3d in phagocytosis. J Exp Med 145: 357
Fehr J, Hofmann V, Kappeler U (1982) Transient reversal of thrombocytopenia in idiopathic thrombocytopenic purpura by high-dose intravenous gammaglobulin. N Engl J Med 306: 1254
Follea G, Mandran B, Dechavanne M (1982) Simultaneous enzymo-immunologic assay of platelet-associated IgG, IgM and C3. A useful tool in assessment of immune thrombocytopenias. Thrombos Res 26: 249
Frank MM (moderator), Schreiber AD, Atkinson JP, Jaffe CJ (discussants) (1977) Pathophysiology of immune hemolytic anemia. Ann Intern Med 87: 210
Gigli I, Nelson RA Jr (1968) Complement-dependent immune phagocytosis. I. Requirement of C'1, C'4, C'2, C'3. Exp Cell Res 51: 45
Gross B, Haessig A, Luescher EF, Nydegger UE (1983) Monomeric immunoglobulin G preparations for intravenous use inhibit platelet stimulation by polymeric IgG. Br J Haematol 53: 289
Imbach P, Barandun S, d'Apuzzo V, Baumgartner C, Hirt A, Morell A, Rossi E, Schöni M, Vest M, Wagner HP (1981) High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1: 1128
Imbach P, Jungi TW (1983) Possible mechanisms of intravenous immunoglobulin treatment in childhood idiopathic thrombocytopenic purpura (ITP). Blut 46: 117
Karas SP, Rosse WF, Kurlander RJ (1982) Characterization of the IgG-Fc receptor on human platelets. Blood 60: 1277
Kayser W, Mueller-Eckhardt C, Budde V, Schmidt RE (1981) Complement-fixing platelet autoantibodies in autoimmune thrombocytopenia. Am J Haematol 11: 213
Kelton JG, Denomme G (1982) The quantitation of platelet-associated IgG on cohorts of platelets separated from healthy individuals by buoyant density centrifugation. Blood 60: 136
Lurhuma AZ, Riccomi H, Masson PL (1977) The occurrence of circulating immune complexes and viral antigens in idiopathic thrombocytopenic purpura. Clin Exp Immunol 28: 49
Masson PL (1979) The therapeutic use of human immunoglobulin selected on the basis of their antibody activity against circulating antigens. In: Peeters H, Wright P (eds) Plasma protein pathology. Pergamon Press, Oxford
Mueller-Eckhardt C, Salama A, Kiefel V, Küenzlen E, Förster C (1984) A New Concept for the Effector Mechanism of Intravenous Immunoglobulin in Hemocytopenias. Blut 48: 353
Nel SD, Stevens K, Mouton A, Pretorius FJ (1983) Platelet-bound IgM in autoimmune thrombocytopenia. Blood 61: 119
Newland AC, Treleaven JG, Minchinton RM, Waters AH (1983) High-dose intravenous IgG in adults with autoimmune thrombocytopenia. Lancet 1: 84
Newman SL, Musson RA, Henson PM (1980) Development of functional complement receptors during in vitro maturation of human monocytes into macrophages. J Immunol 125: 2236
Pfueller SL, Cosgrove L, Firken B, Tear P (1981) Relationship of raised platelet IgG in thrombocytopenia to total platelet protein content. Br J Haematol 49: 239
Pfueller SL, Weber S, Luescher EF (1977) Studies of the mechanism of the human platelet release reaction induced by immunologic stimuli. III. Relationship between the binding of soluble IgG aggregates to the Fc-receptor and cell response in the presence and absence of plasma. J Immunol 118: 514
Ross GD (1982) Structure and function of membrane complement receptors. Fed Proc 41: 3089 and personal communication.
Winiarski J, Holm G (1983) Platelet associated immunoglobulins and complement in idiopathic thrombocytopenic purpura. Clin Exp Immunol 53: 201
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Supported by the Swiss National Science Foundation and the Stanley Thomas Johnson Foundation
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Jungi, T.W., Imbach, P. & Barandun, S. Specific and nonspecific mechanisms of action of immunoglobulin G in therapy of idiopathic thrombocytopenic purpura (ITP). Blut 48, 345–351 (1984). https://doi.org/10.1007/BF00319961
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DOI: https://doi.org/10.1007/BF00319961