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Wirkmechanismen von Immunglobulinen

  • R. Gold
  • P. Späth

Zusammenfassung

Die zur Therapie von Autoimmunerkrankungen gegebenen intravenösen 7S-Immunglobuline (IgG) besitzen in vivo eine Halbwertszeit von 3 bis 4 Wochen. Als klassische Wirkmechanismen der Immunglobuline gelten die Vermittlung der erworbenen und teils auch angeborenen humoralen Immunität, also die Erkennung und schließlich Elimination von pathogenen Erregern sowie ihrer Metaboliten. Zudem können Fraktionen der Immunglobuline und die in den Präparationen enthaltenen aktiven, löslichen Immunmoleküle eine regulatorische Funktion auf die zelluläre und humorale Immunität des menschlichen Organismus ausüben. Dadurch können sie zur Begrenzung z.B. von Entzündungsreaktionen beitragen, weshalb Immunglobulinpräparate mittlerweile breiten Eingang in die Therapie neurologischer Autoimmunerkrankungen gefunden haben. Wir besprechen im Folgenden die Vielzahl von Wirkmechanismen, die in vitro, ex vivo und in vivo beschrieben wurden. Von einer vergleichenden Bewertung der therapeutischen Relevanz der Mechanismen in der Neurologie möchten wir absehen, weil unserer Ansicht nach bei der klinischen Anwendung von Immunglobulinpräparaten immer alle Wirkungen zum Zuge kommen können und die Relevanz einzelner Mechanismen letztlich vom Status des Empfängers abhängt. Das Zusammenwirken der vielfältigen Mechanismen macht es erst möglich, dass die wohl eher milden Einzeleffekte sich zu therapeutischer Bedeutung summieren können.

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Literatur

  1. 1.
    Abdou MI, Wall H, Lindsley HB, Hasley JF, Susuki T (1981) Network theory in autoimmunity: in vitro suppression of serum anti-DNA antibody binding to DNA by anti-idiotypic antibody in systemic lupus erythematosus. J Clin Invest 67:1297–1304PubMedCrossRefGoogle Scholar
  2. 2.
    Achiron A, Margalit R, Hershkoviz R et al (1994) Intravenous immunoglobulin treatment of experimental T cell-mediated autoimmune disease. Upregulation of T-cell proliferation and downregulation of tumor necrosis factor secretion. J Clin Invest 93:600–605PubMedCrossRefGoogle Scholar
  3. 3.
    Alder LBA, Morgan LA, Spickett GP (1996) Contribution of stabilizing agents present in intravenous immunoglobulin preparations to modulation of mononuclear cell proliferation in vitro. Scand J Immunol 44:585–591PubMedCrossRefGoogle Scholar
  4. 4.
    Amran D, Renz H, Lack G, Bradley K, Gelfand EW (1994) Suppression of cyto-kine-dependent human T-cell proliferation by intravenous immunoglobulin. Clin Immunol Immunopathol 73:180–186PubMedCrossRefGoogle Scholar
  5. 5.
    Andersson J, Fehniger T, Björk L, Andersson U (1996) Intravenous immune globulin has effects on superantigen-induced cytokine synthesis. Infusionsther Trans-fus Med 23:7–14Google Scholar
  6. 6.
    Andersson JP, Andersson UG (1990) Human intravenous immunoglobulin modulates monokine production in vitro. Immunology 71:372–376PubMedGoogle Scholar
  7. 7.
    Andersson UG, Björk L, Skansen-Saphir U, Andersson JP (1993) Down-regulation of cytokine production and interleukin-2 receptor expression by pooled human IgG. Immunology 79:211–216PubMedGoogle Scholar
  8. 8.
    Archelos JJ, Previtali SC, Hartung HP (1999) The role of integrins in immune-mediated diseases of the nervous system. Trends Neurosci. 22:30–38PubMedCrossRefGoogle Scholar
  9. 9.
    Asakura K, Miller DJ, Murray K, Bansal R, Pfeiffer SE, Rodriguez M (1996) Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelina-tion, recognizes an antigen on the surface of oligodendrocytes. J Neurosci Res 43:273–281PubMedCrossRefGoogle Scholar
  10. 10.
    Aukrust P, Müller F, Svenson M, Nordoy I, Bendtzen K, Froland SS (1999) Administration of intravenous immunoglobulin (IVIG) in vivo-down-regulatory effects on the IL-1 system. Clin Exp Immunol 115:136–143PubMedCrossRefGoogle Scholar
  11. 11.
    Ballow M, White W, Desbonnet C (1989) Modulation of in vitro synthesis of immunoglobulin and the induction of suppressor activity by therapy with intravenous immune globulin. J Allergy Clin Immunol 84:595–602PubMedCrossRefGoogle Scholar
  12. 12.
    Basta M, Dalakas M (1994) High-dose intravenous immunoglobulin exerts its beneficial effect in patients with dermatomyositis by blocking endomysial deposition of activated complement fragments. J Clin Invest 94:1729–1735PubMedCrossRefGoogle Scholar
  13. 13.
    Basta M, Kirshbom P, Frank MM, Fries LF (1989) Mechanism of therapeutic effect of high-dose intravenous immunoglobulin. Attenuation of acute, complement-dependent immune damage in a guinea pig model. J Clin Invest 84:1974–1981PubMedCrossRefGoogle Scholar
  14. 14.
    Besinger U, Fateh-Moghadam A, Knorr-Held S, Wick M, Kissel H, Albitz M (1987) Immunomodulation in myasthenia gravis by high-dose intravenous 7S-immunoglobulins. Ann N Y Acad Sci 505:828–831CrossRefGoogle Scholar
  15. 15.
    Bijsterbosch MK, Klaus GGB (1985) Cross-linking of surface immunoglobulin and Fc receptors on B lymphocytes inhibits stimulation of inositol phospholipid breakdown via the antigen receptors. J Exp Med 162:1825–1836PubMedCrossRefGoogle Scholar
  16. 16.
    Blasczyk R, Westhoff U, Grosse Wilde H (1993) Soluble CD4, CD8, and HLA molecules in commercial immunoglobulin preparations. Lancet 341:789–790PubMedCrossRefGoogle Scholar
  17. 17.
    Bleeker WK, Teeling JL, Verhoeven AJ et al (2000) Vasoactive side effects of intravenous immunoglobulin preparations in a rat model and their treatment with recombinant platelet-activating factor acetylhydrolase. Blood 95:1856–1861PubMedGoogle Scholar
  18. 18.
    Burastero SE, Casali P, Wilder RL et al (1988) Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 168:1979–1992PubMedCrossRefGoogle Scholar
  19. 19.
    Clinical Immunology Committee IUoISaWHO (1982) Appropriate uses of human immunoglobulin in clinical practice. Bull World Health Organ 60:43–47Google Scholar
  20. 20.
    Cohn EJ, Strong LE, Hughes WL et al (1946) Preparation and properties of serum and plasma proteins. I. A system for the separation into fractions of the protein and lipoprotein components of biological issues and fluids. J Am Chem Soc 68:459–475PubMedCrossRefGoogle Scholar
  21. 21.
    Dalakas MC (1998) The use of intravenous immunoglobulin for neurologic diseases. Neurology 51:S1–S1Google Scholar
  22. 22.
    Dalakas MC, Illa I, Dambrosia JM et al (1993) Efficacy of high-dose intravenous immunoglobulin in the treatment of dermatomyositis: a double-blind, placebo-controlled study. N Engl J Med 329:1993–2000PubMedCrossRefGoogle Scholar
  23. 23.
    De Magistris MT, Alexander J, Coggeshall M et al (1992) Antigen analog major histocompatibility complexes act as antagonists of the T cell receptor. Cell 68:625–634PubMedCrossRefGoogle Scholar
  24. 24.
    Debre M, Bonnet M-C, Fridman W-H et al (1993) Infusion of Fcg fragments for treatment of children with acute immune thrombocytopenic purpura. Lancet 342:945–949PubMedCrossRefGoogle Scholar
  25. 25.
    Drews J (1986) Immunpharmakologie. Springer, Berlin HeidelbergCrossRefGoogle Scholar
  26. 26.
    Enders U, Karch H, Toyka KV et al (1993) The spectrum of immune responses to Campylobacter jejuni and glycoconjugates in Guillain-Barre syndrome and in other neuroimmunological disorders. Ann Neurol 34:136–144PubMedCrossRefGoogle Scholar
  27. 27.
    Fateh-Moghadam A, Wick M, Besinger U, Geursen RG (1984) High-dose intravenous gammaglobulin for myasthenia gravis. Lancet 1:848–849PubMedCrossRefGoogle Scholar
  28. 28.
    Frank MM, Basta M, Fries LF (1992) The effects of intravenous immune globulin on complement-dependent immune damage of cells and tissues. Clin Immunol Immunopathol 62:S82–S86PubMedCrossRefGoogle Scholar
  29. 29.
    Frigerio S, Silei V, Ciusani E, Massa G, Lauro GM, Salmaggi A (2000) Modulation of Fas-Ligand (Fas-L) on human microglial cells: an in vitro study. J Neuroimmu-nol 105:109–114CrossRefGoogle Scholar
  30. 30.
    Gabriel CM, Gregson NA, Redford EJ, Davies M, Smith KJ, Hughes RAC (1997) Human immunoglobulin ameliorates rat experimental autoimmune neuritis. Brain 120:1533–1540PubMedCrossRefGoogle Scholar
  31. 31.
    Geng YM, Shane RB, Berencsi K et al (2000) Chlamydia pneumoniae inhibits apoptosis in human peripheral blood mononuclear cells through induction of ILIO. J Immunol 164:5522–5529PubMedGoogle Scholar
  32. 32.
    Godeau B, Oksenhendler E, Brossard Y et al (1996) Treatment of chronic autoimmune thrombocytopenic purpura with monoclonal anti-D. Transfusion 36:328–330PubMedCrossRefGoogle Scholar
  33. 33.
    Grosse-Wilde H, Blasczyk R, Westhoff U (1992) Soluble HLA class I and class II concentrations in commercial immunoglobulin preparations. Tissue Antigens 39:74–77PubMedCrossRefGoogle Scholar
  34. 34.
    Hartung HP, Zielasek J, Jung S, Toyka KV (1996) Effector mechanisms in demyeli-nating neuropathies. Rev Neurol (Paris) 152:320–327Google Scholar
  35. 35.
    Hasemann CA, Capra JD (1989) Immunoglobulins: Structure and function. In: Paul WE (ed) Fundamental Immunology. Raven Press, New York, pp 209–233Google Scholar
  36. 36.
    Hauser SL, Oksenberg JR, Lincoln R et al (2000) Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS. Neurology 54:1859–1861PubMedGoogle Scholar
  37. 37.
    Herman A, Kappler JW, Marrack P, Pullen AM (1991) Superantigens: mechanism of T-cell stimulation and role in immune responses. Ann Rev Immunol 9:745–772CrossRefGoogle Scholar
  38. 38.
    Imbach P, Barandun S, d’Apuzzo V et al (1981) High dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura. Lancet 1:1228–1231PubMedCrossRefGoogle Scholar
  39. 39.
    Jordan SC (1989) Intravenous gamma-globulin therapy in systemic lupus erythematosus and immune complex disease. Clin Immunol Immunopathol 53:S164–S169PubMedCrossRefGoogle Scholar
  40. 40.
    Kamolvarin N, Hemachudha T, Ongpipattanakul B, Phanuphak P, Viddayakorn P, Sueblinvong T (1989) Plasma C3c changes in myasthenia gravis patients receiving high-dose intravenous immunoglobulin during crisis. Acta Neurol Scand 80:324–326PubMedCrossRefGoogle Scholar
  41. 41.
    Kaveri S, Vassilev T, Hurez V et al (1996) Antibodies to a conserved region of HLA class molecules, capable of modulating CD8 T cell-mediated function, are present in pooled normal immunoglobulin for therapeutic use. J Clin Invest 97:865–869PubMedCrossRefGoogle Scholar
  42. 42.
    Kaveri SV, Dietrich G, Hurez V, Kazatchkine MD (1991) Intravenous immunoglobulins (IVIg) in the treatment of autoimmune diseases (published erratum appears in Clin Exp Immunol 1992 88(2):373). Clin Exp Immunol 86:192–198PubMedCrossRefGoogle Scholar
  43. 43.
    Kekow J, Reinhold D, Pap T, Ansorge S (1998) Intravenous immunoglobulins and transforming growth factor β. Lancet 351:184–185PubMedCrossRefGoogle Scholar
  44. 44.
    Klein J (1991) Immunologic VCH Verlagsgesellschaft, WeinheimGoogle Scholar
  45. 45.
    Kondo N, Ozawa T, Mushiake K et al (1991) Suppression of immunoglobulin production of lymphocytes by intravenous immunoglobulin. J Clin Immunol 11:152–158PubMedCrossRefGoogle Scholar
  46. 46.
    Lacroix-Desmazes S, Kaveri SV, Mouthon L et al (1998) Self-reactive antibodies (natural autoantibodies) in healthy individuals. J Immunol Methods 216:117–137PubMedCrossRefGoogle Scholar
  47. 47.
    Lam L, Whitsett CF, McNicholl JM, Hodge TW, Hooper J (1993) Immunologically active proteins in intravenous immunoglobulin. Lancet 342:678–678PubMedCrossRefGoogle Scholar
  48. 48.
    Leung DY, Kurt-Jones E, Newburger JW, Cotran RS, Burns JC, Prober J (1989) Endothelial cell activation of high interleukin-1 secretion in the pathogenesis of acute Kawasaki disease. Lancet 11:1298–1298CrossRefGoogle Scholar
  49. 49.
    Lundkvist I, van Doom PA, Vermeulen M, Brand A (1993) Spontaneous recovery from the Guillain-Barre syndrome is associated with anti-idiotypic antibodies recognizing a cross-reactive idiotype on anti-neuroblastoma cell line antibodies. Clin Immunol Immunopathol 67:192–198PubMedCrossRefGoogle Scholar
  50. 50.
    Lutz HU, Stammler P, Jelezarova E, Nater M, Spath PJ (1996) High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes. Blood 88:184–193PubMedGoogle Scholar
  51. 51.
    Marchalonis JJ, Kaymaz H, Dedeoglu F, Schluter SF, Yocum DE, Edmundson AB (1992) Human autoantibodies reactive with synthetic autoantigens from T-cell receptor β chain. Proc Natl Acad Sci USA 89:3325–3329PubMedCrossRefGoogle Scholar
  52. 52.
    Masson PL (1993) Elimination of infectious antigens and increase of IgG catabolism as possible modes of action of IVIg. J Autoimmun 6:683–689PubMedCrossRefGoogle Scholar
  53. 53.
    McGavern D, Asakura K, Rodriguez M (1999) Do antibodies stimulate myelin repair in multiple sclerosis? The Neuroscientist 5:19–28CrossRefGoogle Scholar
  54. 54.
    Mellman I, Koch T, Healey G et al (1988) Structure and function of Fc receptors on macrophages and lymphocytes. J Cell Sci 89 (S):45–65Google Scholar
  55. 55.
    Miller DJ, Sanborn KS, Katzmann JA, Rodriguez M (1994) Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis. J Neurosci 14:6230–6238PubMedGoogle Scholar
  56. 56.
    Miyagi F, Horiuchi H, Nagata I et al (1997) Fc portion of intravenous immunoglobulin suppresses the induction of experimental allergic neuritis. J Neuroimmunol 78:127–131PubMedCrossRefGoogle Scholar
  57. 57.
    Mouthon L, Kaveri SV, Spalter SH et al (1996) Mechanisms of action of intravenous immune globulin in immune mediated diseases. Clin Exp Immunol 104:3–9PubMedGoogle Scholar
  58. 58.
    Nachbaur D, Herold M, Eibl B et al (1997) A comparative study of the in vitro immunomodulatory activity of human intact immunoglobulin (7S IVIG), F(ab’)2 fragments (5S IVIG) and Fc fragments. Evidence for post-transcriptional IL-2 modulation. Immunology 90:212–218PubMedCrossRefGoogle Scholar
  59. 59.
    Newburger JW, Takahashi M, Beiser AS et al. (1991) A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N J Engl Med 324(23):1633–1639CrossRefGoogle Scholar
  60. 60.
    Ochsenbein AF, Fehr T, Lutz C et al (1999) Control of early viral and bacterial distribution and disease by natural antibodies. Science 286:2156–2159PubMedCrossRefGoogle Scholar
  61. 61.
    Okuda Y, Sakoda S, Saeki Y, Kishimoto T, Yanagihara T (2000) Enhancement of Th2 response in IL-6-deficient mice immunized with myelin oligodendrocyte glycoprotein. J Neuroimmunol 105:120–123PubMedCrossRefGoogle Scholar
  62. 62.
    Olivares-Villagómez D, Wensky AK, Wang YJ, Lafaille JJ (2000) Repertoire requirements of CD4+ T cells that prevent spontaneous autoimmune encephalomyelitis. J Immunol 164:5499–5507PubMedGoogle Scholar
  63. 63.
    Pashov A, Dubey C, Kaveri SV et al (1998) Normal immunoglobulin G protects against experimental allergic encephalomyelitis by inducing transferable T-cell unresponsiveness to myelin basic protein. Eur J Immunol 28:1823–1831PubMedCrossRefGoogle Scholar
  64. 64.
    Pavelko KD, van Engelen BGM, Rodriguez M (1998) Acceleration in the rate of CNS remyelination in lysolecithin induced demyelination. J Neurosci 18:2498–2505PubMedGoogle Scholar
  65. 65.
    Perosa F, Rizzi R, Pulpito V, Dammacco F (1995) Soluble CD4 antigen reactivity in intravenous immunoglobulin preparations: is it specific? Clin Exp Immunol 99:16–20PubMedCrossRefGoogle Scholar
  66. 66.
    Petri IB, Lörintz A, Berek I (1986) Further investigation of nonspecific biological substance in anti-Rh(D) preparations. Vox Sang 51:291CrossRefGoogle Scholar
  67. 67.
    Prasad NK, Papoff G, Zeuner A et al (1998) Therapeutic preparations of normal polyspecific IgG (IVIg) induce apoptosis in human lymphocytes and monocytes: A novel mechanism of action of IVIg involving the Fas apoptotic pathway. J Immunol 161:3781–3790PubMedGoogle Scholar
  68. 68.
    Rodriguez M, Lennon VA (1990) Immunoglobulins promote remyelination in the central nervous system. Ann Neurol 27:12–17PubMedCrossRefGoogle Scholar
  69. 69.
    Rodriguez M, Miller DJ, Lennon VA (1996) Immunoglobulins reactive with myelin basic protein promote CNS remyelination. Neurology 46:538–545PubMedGoogle Scholar
  70. 70.
    Roitt IM (1989) Leitfaden der Immunologic: Steinkopff, DarmstadtGoogle Scholar
  71. 71.
    Romer J, Spath PJ, Skvaril F, Nydegger UE (1982) Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to staphylococcus protein A. Vox Sang 42:74–80PubMedGoogle Scholar
  72. 72.
    Ronda N, Haury M, Nobrega A, Coutinho A, Kazatchkine MD (1994) Selectivity of recognition of variable (V) regions of autoantibodies by intravenous immunoglobulin (IVIg). Clin Immunol Immunopathol 70:124–128PubMedCrossRefGoogle Scholar
  73. 73.
    Ross C, Svenson M, Hansen MB, Vejlsgaard GL, Bendtzen K (1995) High avidity IFN-neutralizing antibodies in pharmaceutically prepared human IgG. J Clin Invest 95:1974–1978PubMedCrossRefGoogle Scholar
  74. 74.
    Roux KH, Tankersley DL (1990) A view of the human idiotypic repertoire. Electron microscopic and immunologic analyses of spontaneous idiotype-anti-idio-type dimers in pooled human IgG. J Immunol 144:1387–1395PubMedGoogle Scholar
  75. 75.
    Schmidt RE, Budde V, Schäfer G, Stroehmann I (1981) High-dose intravenous gamma globulin for idiopathic thrombocytopenic purpura. Lancet 2:475–476PubMedCrossRefGoogle Scholar
  76. 76.
    Sharief MK, Ingram DA, Swash M, Thompson EJ (1999) IV immunoglobulin reduces circulating proinflammatory cytokines in Guillain-Barre syndrome. Neurology 52:1833–1838PubMedGoogle Scholar
  77. 77.
    Sinclair NRS (1991) Fc-receptor-mediated immunomodulation. Immunol Today 12:46PubMedCrossRefGoogle Scholar
  78. 78.
    Smith NA, Chakraverety RK, Broughton BJ (1998) The successful treatment of idiopathic thrombocytopenic purpura with the low dose, non-specific IgG component of anti-D immunoglobulin. Clin Lab Hematol 12:131–136Google Scholar
  79. 79.
    Späth PJ (1999) Structure and function of immunoglobulins. Sepsis 3:197–218CrossRefGoogle Scholar
  80. 80.
    Stangel M, Compston A, Scolding NJ (1999) Polyclonal immunoglobulins for intravenous use do not influence the behaviour of cultured oligodendrocytes. J Neu-roimmunol 96:228–233Google Scholar
  81. 81.
    Stangel M, Compston A, Scolding NJ (2000) Oligodendroglia are protected from antibody-mediated complement injury by normal immunoglobulins („IVIg“). J Neuroimmunol 103:195–201PubMedCrossRefGoogle Scholar
  82. 82.
    Stangel M, Hartung HP, Marx P, Gold R (1998) Intravenous immunoglobulin treatment of neurological autoimmune diseases. J Neurol Sci 153:203–214PubMedCrossRefGoogle Scholar
  83. 83.
    Stangel M, Schumacher HC, Ruprecht K, Boegner F, Marx P (1997) Immunoglobulins for intravenous use inhibit TNFα cytotoxicity in vitro. Immunol Invest 26:569–578PubMedCrossRefGoogle Scholar
  84. 84.
    Sultan Y, Kazatchkine MD, Maisonneuve P, Nydegger UE (1984) Anti-idiotypic suppression of autoantibodies to factor VIII (antihaemophilic factor) by high-dose intravenous gammaglobulin. Lancet 2:765–768PubMedCrossRefGoogle Scholar
  85. 85.
    Suzuki N, Sakane T, Engleman EG (1990) Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus. J Clin Invest 85:238–247PubMedCrossRefGoogle Scholar
  86. 86.
    Svenson M, Hansen MB, Bendtzen K (1993) Binding of cytokines to pharmaceutically prepared human immunoglobulin. J Clin Invest 92:2533–2539PubMedCrossRefGoogle Scholar
  87. 87.
    Takei S, Arora YK, Walker SM (1993) Intravenous immunoglobulin contains specific antibodies inhibitory to activation of T cells by staphylococcal toxin superantigens (see comment). J Clin Invest 91:602–607PubMedCrossRefGoogle Scholar
  88. 88.
    Terness P, Opelz G (1998) Natural antiimmunoglobulin autoantibodies: Irrelevant by-products or immunoregulatory molecules? Int Arch Allergy Immunol 115:270–277PubMedCrossRefGoogle Scholar
  89. 89.
    Toyka KV, Hartung HP, Hohlfeld R (1987) Klinische Neuroimmunologie. Diagnostik, Pathophysiologic Therapie. VCH Verlagsgesellschaft, WeinheimGoogle Scholar
  90. 90.
    van der Meche FGA, Schmitz PIM, and the Dutch Guillain-Barre study group (1992) A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. N Engl J Med 326:1123–1129PubMedCrossRefGoogle Scholar
  91. 91.
    van Doom PA, Rossi F, Brand A, van Lint M, Vermeulen M, Kazatchkine MD (1990) On the mechanism of high-dose intravenous immunoglobulin treatment of patients with chronic inflammatory demyelinating polyneuropathy. J Neuroimmunol 29:57–64CrossRefGoogle Scholar
  92. 92.
    van Doom PA, Vermeulen M, Brand A, Mulder PG, Busch HF (1991) Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy. Clinical and laboratory characteristics associated with improvement. Arch Neurol 48:217–220CrossRefGoogle Scholar
  93. 93.
    van Engelen BGM, Benders AAGM, Wevers RA, Gabreis FJM, Renier WO, Veer-kamp JH (1998) Intravenous immunoglobulin preparation increases myoplasmic calcium concentration by activating the dihydropyridine-ryanodine receptor complex. J Neurol Sci 156:35–40PubMedCrossRefGoogle Scholar
  94. 94.
    Vassilev T, Gelin C, Kaveri SV, Zilber MT, Boumsell L, Kazatchkine MD (1993) Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg). Clin Exp Immunol 92:369–372PubMedCrossRefGoogle Scholar
  95. 95.
    Vassilev TL, Kazatchkine MD, Van Huyen JP et al (1999) Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg). Blood 93:3624–3631PubMedGoogle Scholar
  96. 96.
    Viard I, Wehrli P, Bullani R, et al (1998) Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 282:490–493PubMedCrossRefGoogle Scholar
  97. 97.
    Waldmann TA, Strober W (1969) Metabolism of immunoglobulins. Prog Allergy 13:1–110PubMedGoogle Scholar
  98. 98.
    Xu C, Poirier B, Van Huyen JP, et al (1998) Modulation of endothelial cell function by normal polyspecific human intravenous immunoglobulins — A possible mechanism of action in vascular diseases. Am J Pathol 153:1257–1266PubMedCrossRefGoogle Scholar
  99. 99.
    Yu ZY, Lennon VA (1999) Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 340:227–228PubMedCrossRefGoogle Scholar

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© Steinkopff Verlag Darmstadt 2001

Authors and Affiliations

  • R. Gold
  • P. Späth

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