Advertisement

Herstellung, Verträglichkeit und Virussicherheit von intravenösem Immunglobulin

  • P. Späth
  • C. Kempf
  • R. Gold

Zusammenfassung

Die mehr als hundertjährige Geschichte der klinischen Anwendung von Immunglobulinen fangt mit der antitoxischen Wirkung von tierischen Immunseren an. In der Entwicklung hin zu einem nebenwirkungsarmen und biologisch hoch wirksamen intravenösen Immunglobulinpräparat (IVIg) zieht sich wie ein roter Faden die Inkubation bei tiefem pH in Gegenwart oder Abwesenheit von proteolytischen Enzymen. Die technische Entwicklung ging Hand in Hand mit den klinischen Bedürfnissen und Indikationsfindungen. Letztere haben seit den frühen 80er Jahren eine ungeahnte Ausweitung auf das Gebiet der Immunmodulation erfahren. Der Wunsch nach einer immer effektiveren Immunmodulation und die damit verbundene Verabreichung immer höherer Dosen haben die Probleme von Nebenreaktionen verschärft. Offenbar werden mit den hohen Dosen die Grenzen der Biologie erreicht: Die an die erwünschte Immunmodulation gekoppelte Alloreaktivität der IVIg wirkt sich auf den Organismus aus. Die Frage der Virussicherheit von IVIg ist seit den frühen 80er Jahren von Anwendern und Behörden immer nachhaltiger gestellt worden. Heute sind die Grundsteine von sicheren Blut- und Plasmaprodukten „gute Herstellungspraxis“ und „gute Laborpraxis“. Einer der Eckpfeiler der „guten Herstellungspraxis“ ist die Validierung von Herstellungsverfahren und Analysemethoden. Aufwendige, nach strengen Kriterien durchgeführte und dokumentierte Validierungsstudien zur Virusinaktivierung und Viruselimination sind Voraussetzung für die Zulassung neuer oder die Fortführung der Zulassimg etablierter IVIg. Von den Behörden gewünscht sind 2 für die Virusinaktivierung/Virusabreicherung nachweisbar wirksame Herstellungsschritte, die sich ergänzen. Methoden, die die Virussicherheit von IVIg garantieren sollen, und die Resultate von Validierungsstudien werden an Beispielen erläutert. IVIg, die heute unter strenger Einhaltung der „guten Herstellungspraxis“ produziert werden, gelten betreffend Virusübertragung als weitgehend sicher. Schließlich weisen auch Modellstudien zur Abreicherung von Prionen auf die Sicherheit von IVIg.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Literatur

  1. 1.
    Anonym from the Centers for Disease Control and Prevention (1994) Outbreak of hepatitis associated with intravenous immunoglobulin administration — United States, October 1993 — June 1994. J Am Med Assoc 272:424–425Google Scholar
  2. 2.
    Anonym by CPMP Biotechnology Working Party (1996) Note for guidance on virus validation studies: The design, contribution and interpretation of studies validating the incativation and removal of viruses. CPMP/BWP/268/95 Final Version 2:1–13Google Scholar
  3. 3.
    Anonym (1997) Creutzfeldt-Jakob disease associated with cadaveric dura mater grafts — Japan, January 1979-May 1996. Mor Mortal Wkly Rep 46:1066–1069Google Scholar
  4. 4.
    Anonym by CPMP (1999) Note for guidance on plasma derived medicinal products. The European Agency for the Evaluation of Medicinal Products — Human Medicines Evaluation Unit CPMP/BWP/269/95 Final Version 2; London, 23 July 1998:1–17Google Scholar
  5. 5.
    Anonym (1999) First outbreak of TT virus in California. AABB Wkly Rep 5:6–6Google Scholar
  6. 6.
    Anonym (1999) NAT testing of solvent-detergent treated fresh frozen plasma. AABB Wkly Rep 5:3–4Google Scholar
  7. 7.
    Anonym (1999) Newly discovered virus may cause non-A, non-E hepatitis. AABB Wkly Rep 5:1–2Google Scholar
  8. 8.
    Anonym (1999) nvCJD in Ireland. AABB Wkly Rep 5:4–4Google Scholar
  9. 9.
    Anonym (1999) VA study finds no link between CJD and plasma derivatives. ABC Newsletter 17:6Google Scholar
  10. 10.
    Anonym (1999) VI Technologies this week expanded its voluntary recall of its solvent-detergent treated pooled plasma, PLAS-SD to include eleven additional lots. ABC Newsl 1999:9–10Google Scholar
  11. 11.
    Anonym (2000) EMEA expert workshop on human TSEs and plasma-derived medicinal products. The European Agency for the Evaluation of Medicinal Products — Human Medicines Evaluation Unit CPMP/BWP/1244/00:1–13Google Scholar
  12. 12.
    Anonym (2000) FDA has advised that it would „consider elimination of (current viral detection) test if data was presented showing a more sensitive test was available. International Blood/Plasma News 17:161Google Scholar
  13. 13.
    Abe K, Inami T, Asano K, Miyoshi C, Masaki N, Hayashi S, Ishikawa K, Takebe Y, Win KM, El-Zayadi AR, Han KH, Zhang DY (1999) TT virus infection is widespread in the general populations from different geographic regions. J Clin Microbiol 37:2703–2705PubMedGoogle Scholar
  14. 14.
    Ahsan N, Palmer BF, Wheeler D, Greenlee RG, Toto RD (1994) Intravenous immunoglobulin-induced osmotic nephrosis. Arch Intern Med 154:1985–1987PubMedCrossRefGoogle Scholar
  15. 15.
    Allain JP (2000) Emerging viruses in blood transfusion. Vox Sang 78:243–248PubMedGoogle Scholar
  16. 16.
    Alter HJ, Nakatsuji Y, Melpolder J, Wages J, Wesley R, Shih JWK, Kim JP (1997) The incidence of transfusion-associated hepatitis G virus infection and its relation to liver disease. N Engl J Med 336:747–754PubMedCrossRefGoogle Scholar
  17. 17.
    Alter MJ, Gallagher M, Morris TT, Moyer LA, Meeks EL, Krawczynski K, Kim JP, Margolis HS (1997) Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection. N Engl J Med 336:741–746PubMedCrossRefGoogle Scholar
  18. 18.
    Amstutz H, Balmer V, Lerch P (1996) High-titer immunoglobulin preparation prepared by affinity chromatography of human plasma fractions. In: Kazatchkine MD, Morell A (eds) Intravenous immunoglobulin — research and therapy. The Parthenon Publishing Group, London, pp 305–306Google Scholar
  19. 19.
    Amstutz H, Lerch PG, Morgenthaler JJ (1997) Verfahren zur Gewinnung von Immunglobulinen aus Fraktionen, die bei der Fraktionierung von menschlichem Blutplasma entstehen. Patent Nr. 9581596.7(EP 0 764 658 A1), 1–10Google Scholar
  20. 20.
    Barandun S (1964) Neue Aspekte und Hypothesen. In: Brandun S (ed) Die Gammaglobulin-Therapie. Karger, Basel 113–120Google Scholar
  21. 21.
    Barandun S, Kaiser M, Dostal V (1961) Zur Frage der intravenösen Gammaglobulinapplikation. Helv Med Acta 28:551–555Google Scholar
  22. 22.
    Barandun S, Kistler P, Jeunet F, Isliker H (1962) Intravenous administration of human γ-globulin. Vox Sang 7:157–174PubMedCrossRefGoogle Scholar
  23. 23.
    Barandun S, Riva G, Spengler GA (1979) Immunologic deficiency: diagnosis, forms and current treatment. In: Bergsman D (ed) Immunological deficiency diseases in man. March of Dimes, New York, pp 40–49Google Scholar
  24. 24.
    Behring E, Kitasato S (1890) Über das Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität bei Thieren. Dt Med Wochenschr 16:1113–1114CrossRefGoogle Scholar
  25. 25.
    Ben-Chetrit E, Putterman C (1992) Transient neutropenia induced by intravenous immune globulin. N Engl J Med 326:270–271PubMedCrossRefGoogle Scholar
  26. 26.
    Bertorini TE, Nance AM, Horner LH, Greene W, Gelfand MS, Jaster JH (1996) Complications of intravenous gammaglobulin in neuromuscular and other diseases. Muscle Nerve 19:388–391PubMedCrossRefGoogle Scholar
  27. 27.
    Bleeker WK, Teeling JL, Verhoeven AJ, Rigter GM, Agterberg J, Tool AT, Koenderman AH, Kuijpers TW, Hack CE (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
  28. 28.
    Bolli R, Brügger R, Hodler G, Maeder W, Spycher MO, Gennari K (1996) IgG dimers in liquid intravenous immunoglobulin preparations. In: Kazatchkine MD, Morell A (eds) Intravenous immunoglobulin — research and therapy. The Parthenon Publishing Group, London, pp 307–308Google Scholar
  29. 29.
    Bons N, Mestre-Frances N, Belli P, Cathala F, Gajdusek DC, Brown P (1999) Natural and experimental oral infection of nonhuman primates by bovine spongiform encephalopathy agents. Proc Natl Acad Sci USA 96:4046–4051PubMedCrossRefGoogle Scholar
  30. 30.
    Bournouf-Radesovich M (1995) Securité virale des préparations d’immunoglobulines G intraveineuses à usage thérapeutique. Transfus Clin Biol 3:167–179CrossRefGoogle Scholar
  31. 31.
    Bower RL, Brey RL, Rogers SJ, Stroncek DF, Jackson CE (1994) Intravenous immunoglobulin-induced neutropenia. Ann Neurol 36:291Google Scholar
  32. 32.
    Brambell FWR, Hemmings WA, Morris IG (1964) A theoretical model of gammaglobulin catabolism. Nature 203:1352–1355PubMedCrossRefGoogle Scholar
  33. 33.
    Brannagan TH, Nagle KJ, Lange DJ, Rowland LP (1996) Complications of intravenous immune globulin treatment in neurologic disease. Neurology 47:674–677PubMedGoogle Scholar
  34. 34.
    Brown KL, Stewart K, Ritchie DL, Mabbott NA, Williams A, Fraser H, Morrison WI, Bruce ME (1999) Scrapie replication in lymphoid tissues depends on prion protein-expressing follicular dendritic cells. Nat Med 5:1308–1312PubMedCrossRefGoogle Scholar
  35. 34 a.
    Brown P (2000) BSE and transmission through blood. Lancet 356:955–956PubMedCrossRefGoogle Scholar
  36. 35.
    Brox AG, Cournoyer D, Sternbach M, Spurll G (1987) Hemolytic anemia following intravenous gammaglobulin administration. Am J Med 82:633–635PubMedCrossRefGoogle Scholar
  37. 36.
    Bruce ME, Will RG, Ironside JW, McConnell I, Drummond D, Suttie A, McCardle L, Chree A, Hope J, Birkett C, Cousens S, Fraser H, Bostock CJ (1997) Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:498–501PubMedCrossRefGoogle Scholar
  38. 37.
    Bruton OC (1952) Agammaglobulinemia. Pediatrics 9:722–728Google Scholar
  39. 38.
    Burckhardt JJ (1999) Assessment of needs for plasma for fractionation in Europe. Biologicals 27:337–341PubMedCrossRefGoogle Scholar
  40. 39.
    Bush MP (2000) HIV, HBV and HCV: New developments related to transfusion safety. Vox Sang 78:253–256CrossRefGoogle Scholar
  41. 40.
    Casteels-Van Daele M, Wijndaele L, Hanninck K, Gillis P, Jesse V (1990) Intravenous immune globulin and acute aseptic meningitis (letter). N Engl J Med 323:614–615Google Scholar
  42. 41.
    Caughey B (2000) Transmissible spongiform encephalopathies, amyloidoses and yeast prions: Common threads? Nat Med 6:751–754PubMedCrossRefGoogle Scholar
  43. 42.
    Chen C, Danekas LH, Ratko TA, Vlasses PH, Matuszewski KA (2000) A multicenter drug use surveillance of intravenous immunoglobulin utilization in US academic health centers. Ann Pharmacother 34:295–299PubMedCrossRefGoogle Scholar
  44. 43.
    Christian CL (1960) Studies on aggregated γ-globulin. J Immunol 84:112–121PubMedGoogle Scholar
  45. 44.
    Chudy M, Budek I, Keller-Stanislawski B, McCaustland KA, Neidhold S, Robertson BH, Nübling CM, Seitz R, Löwer J (1999) A new cluster of hepatitis A infection in hemophiliacs traced to a contaminated plasma pool. J Med Virol 57:91–99PubMedCrossRefGoogle Scholar
  46. 45.
    Cohn EJ (1945) Blood proteins and their therapeutic value. Science 101:51–56PubMedCrossRefGoogle Scholar
  47. 46.
    Cohn EJ, Gurd FRN, Surgenor DM, Barnes BA, Brown RK, Derouaux G, Gillespie JM, Kahnt FW, Lever WF, Liu CH, Mittelman D, Mouton RF, Schmid K, Uroma E (1950) J Am Chem Soc 72:465–474CrossRefGoogle Scholar
  48. 47.
    Cohn EJ, Luetscher JA, Oncley JL, Armstrong SH Jr, Davis BD (1940) Preparations and proteries of serum and plasma proteins. III. Size and charge of proteins separating upon equilibration across membranes with ethanol-water mixtures of controlled pH, ionic strength and temperature. J Am Chem Soc 62:3396–3400CrossRefGoogle Scholar
  49. 48.
    Cohn EJ, Strong LE, Hughes WLJ, Mulford DJ, Asworth JN, Melin M, Taylor HL (1946) Preparation and properties of serum and plasma proteins. IV: A system for the separation into fractions of the protein and lipoprotein components of biological tissues and fluids. J Am Chem Soc 68:459–475PubMedCrossRefGoogle Scholar
  50. 49.
    Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383:685–690PubMedCrossRefGoogle Scholar
  51. 50.
    Collins S, Law MG, Fletcher A, Boyd A, Kaldor J, Masters CL (1999) Surgical treatment and risk of sporadic Creutzfeldt-Jakob disease: a case-control study. Lancet 353:693–697PubMedCrossRefGoogle Scholar
  52. 51.
    Constantinescu CS, Chang AP, McCluskey LF (1993) Recurrent migraine and intravenous immune globulin therapy. N Engl J Med 329:583–584PubMedCrossRefGoogle Scholar
  53. 52.
    Crowe JH, Crowe LM, Carpenter JF, Aurell Wistrom C (1987) Satbilization of dry phospholipid bylayers and proteins by sugars. Biochem J 242:1–10PubMedGoogle Scholar
  54. 53.
    Cunningham-Rundles C, Day NK, Wahn V, Smithwick EM, Siegal FP, Gupta S, Good RA (1981) Reactions to intravenous gammaglobulin infusions and immune complex formation. In: Anonymous Immunohemotherapy. Academic Press, London, pp 447–449Google Scholar
  55. 54.
    Dalakas MC (1994) High-dose intravenous immunoglobulin and serum viscosity: Risk of precipitating thromboembolic events. Neurology 44:223–226PubMedGoogle Scholar
  56. 55.
    Desai SM, Muerhoff AS, Leary TP, Erker JC, Simons JN, Chalmers ML, Birkenmey-er LG, Pilot-Matias TJ, Mushahwar IK (1999) Prevalence of TT virus infection in US blood donors and populations at risk for acquiring parenterally transmitted viruses. J Infect Dis 179:1242–1244PubMedCrossRefGoogle Scholar
  57. 56.
    Deutsch HF, Gosting LJ, Alberty RA, Williams JW (1946) Biophysical studies of blood plasma proteins. III. Recovery of gamma-globulin from human blood protein mixtures. J Biol Chem 164:109PubMedGoogle Scholar
  58. 57.
    Eibl MM, Wolf HM, Furnkranz H, Rosenkranz A (1988) Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding. N Engl J Med 319:1–7PubMedCrossRefGoogle Scholar
  59. 58.
    Fernandez-Lopez MJ, van Everbroeck B, Pals P, Martin JJ, Cras P (1998) Creutzfeldt-Jakob disease and blood transfusion. Acta Neurol Belg 98:247–251PubMedGoogle Scholar
  60. 59.
    Feucht HH, Fischer L, Sterneck M, Broelsch CE, Laufs R (1997) GB virus C transmission by blood products. Lancet 349:435PubMedCrossRefGoogle Scholar
  61. 60.
    Feucht HH, Zöllner B, Polywka S, Knödler B, Schröter M, Nolte H, Laufs R (1997) Prevalence of hepatitis G viremia among healthy subjects, individuals with liver disease, and persons at risk for parenteral transmission. J Clin Microbiol 35:767–768PubMedGoogle Scholar
  62. 61.
    Flora K, Schiele M, Benner K, Montanaro A, Johnston W, Whitham R, Press R (1996) An outbreak of acute hepatitis C among recipients of intravenous immunoglobulin. Ann Allergy Asthma Immunol 76:160–162PubMedCrossRefGoogle Scholar
  63. 62.
    Foster PR (1999) Assessment of the potential of plasma fractionation processes to remove causative agents of transmissible spongiform encephalopathy. Transfus Med 9:3–14PubMedCrossRefGoogle Scholar
  64. 63.
    Ghani AC, Donnelly CA, Ferguson NM, Anderson RM (2000) Assessment of the prevalence of vCJD through testing tonsils and appendices for abnormal prion protein. Proc R Soc Lond B Biol Sci 267:23–29CrossRefGoogle Scholar
  65. 64.
    Gomperts ED (1996) Gammagard and reported hepatitis C virus episodes. Clin Ther 18:3–8PubMedCrossRefGoogle Scholar
  66. 65.
    Gronski P, Hofstaetter T, Kanzy EJ, Lüben G, Seiler FR (1983) S-Sulfonation: a reversible chemical modification of human immunoglobulin permitting intravenous application. I. Physicochemical and binding properties of S-sulfonated and reconstituted IgG. Vox Sang 45:144–154PubMedCrossRefGoogle Scholar
  67. 66.
    Hao YL, Ingham KC, Wickerhauser M (1980) Fractional precipitation of proteins with polyethylene glycol. In: Curling JM (ed) Methods of plasma protein fractionation. Academic Press, London, pp 57–74Google Scholar
  68. 67.
    Harkness K, Howell SJ, Davies-Jones GAB (1996) Encephalopathy associated with intravenous immunoglobulin treatment for Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 60:586–586PubMedCrossRefGoogle Scholar
  69. 68.
    Hübsch AP, Powell FS, Lerch PG, Doran JE (1993) A reconstituted, apolipoprotein A-I containing lipoprotein reduces tumor necrosis factor release and attenuates shock in endotoxemic rabbits. Circ Shock 40:14–23PubMedGoogle Scholar
  70. 69.
    Hugh-Jones M (1999) Second case of nvCJD brain disorder found in France. Reuters, Communication Feb 2, 2000Google Scholar
  71. 70.
    Ishizaka T, Ishizaka K, Boros T (1961) Biological activity of aggregated γ-globulin IV. J Immunol 87:433–438Google Scholar
  72. 71.
    Jackson BR, Aubuchon JP, Birkmeyer JD (1999) Update of cost-effectiveness analysis for solvent-detergent-treated plasma. JAMA 282:329PubMedCrossRefGoogle Scholar
  73. 72.
    Janeway CA (1970) The development of clinical uses of immunoglobulins: a review. In: Merler E (ed) Immunoglobulins biological aspects and clinical uses. National Academy of Sciences, Washington DC, pp 3–14Google Scholar
  74. 73.
    Janeway CA, Rosen FS (1966) The gamma globulins IV. Therapeutic use of gamma globulins. N Engl J Med 275:826–831PubMedCrossRefGoogle Scholar
  75. 74.
    Jayne DR, Chapel H, Adu D, Misbah S, O’Donoghue D, Scott D, Lockwood CM (2000) Intravenous immunoglobulin for ANCA-associated systemic vasculitis with persistent disease activity. QJM 93:433–439PubMedCrossRefGoogle Scholar
  76. 75.
    Kato K, Fridman WH, Arata Y, Sautes-Fridman C (2000) A conformational change in the Fc precludes the binding of two Fcgamma receptor molecules to one IgG. Immunol Today 21:310–312PubMedCrossRefGoogle Scholar
  77. 76.
    Kempf C, Jentsch P, Poirier B, Barre-Sinoussi F, Morgenthaler JJ, Morell A, Ger-mann D (1991) Virus inactivation during production of intravenous immunoglobulin. Transfusion 31:423–427PubMedCrossRefGoogle Scholar
  78. 77.
    Kempf C, Morgenthaler JJ, Rentsch M, Omar A (1996) Viral safety and manufacturing of an intravenous immunoglobulin. In: Kazatchkine MD, Morell A (eds) Intravenous immunoglobulin research and therapy. The Parthenon Publishing Group, pp 11–18Google Scholar
  79. 78.
    Kistler P, Nitschmann H (1962) Large scale production of human plasma fractions: eight years experience with the alcohol fractionation procedure of Nitschmann, Kistler and Lergier. Vox Sang 7:414–424PubMedCrossRefGoogle Scholar
  80. 79.
    Klein MA, Frigg R, Flechsig E, Raeber AJ, Kalinke U, Bluethmann H, Bootz F, Suter M, Zinkernagel RM, Aguzzi A (1997) A crucial role for B cells in neuroinvasive scrapie. Nature 390:687–690PubMedGoogle Scholar
  81. 80.
    Koffman BM, Dalakas MC (1997) Effect of high-dose intravenous immunoglobulin on serum chemistry, hematology, and lymphocyte subpopulations: Assessments based on controlled treatment trials in patients with neurological diseases. Muscle Nerve 20:1102–1107PubMedCrossRefGoogle Scholar
  82. 81.
    Lang CJ, Heckmann JG, Neundorfer B (1998) Creutzfeldt-Jakob disease via dural and corneal transplants. J Neurol Sci 160:128–139PubMedCrossRefGoogle Scholar
  83. 82.
    Lasmézas CI, Deslys JP, Demaimay R, Adjou KZ, Lamoury F, Dormont D, Robain O, Ironside J, Hauw JJ (1996) BSE transmission to macaques. Nature 381:743–744PubMedCrossRefGoogle Scholar
  84. 83.
    Lee DC, Stenland CJ, Hartwell RC, Ford EK, Cai K, Miller JLC, Gilligan KJ, Ruben-stein R, Fournel M, Petteway SR Jr (2000) Monitoring plasma processing steps with a sensitive Western blot assay for the detection of the prion protein. J Virol Methods 84:77–89PubMedCrossRefGoogle Scholar
  85. 84.
    Lelie PN, Cuijpers HTM, van Rixel CAGM, van Drimmelen AAJ (2000) Risk reduction of HIV-transmission by blood transfusion after introduction of HIV NAT screening. Vox Sang 78 (suppl 1): oral 077Google Scholar
  86. 85.
    Lerch PG, Förtsch V, Hodler G, Bolli R (1996) Production and characterization of a reconstituted high densitiy lipoprotein for therapeutic applications. Vox Sang 71:155–164PubMedCrossRefGoogle Scholar
  87. 86.
    Linnen J, Wages JJ, Zhang-Keck Z-Y, Fry KE, Krawczynski KZ, Alter H, Koonin E, Gallagher M, Alter M, Hadziyannis S, Karayiannis P, Fung K, Nakatsuji Y, Shih WKJ, Young L, Piatak MJ, Hoover C, Fernandez J, Chen S, Zou JC, Morris T, Hy-ams KC, Ismay S, Lifson JD, Hess G, Foung SKH, Thomas H, Bradley D, Margolis H, Kim JP (1996) Molecular cloning and disease association of hepatitis G virus: a transfusion-transmissible agent. Science 271:505–508PubMedCrossRefGoogle Scholar
  88. 86 a.
    Levy JB, Pusey CD (2000) Nephrotoxicity of intravenous Immunglobulin. Quart J Med 93:751–755CrossRefGoogle Scholar
  89. 87.
    Mabbott NA, MacKay F, Minns F, Bruce ME (2000) Temporary inactivation of follicular dendritic cells delays neuroinvasion of scrapie. Nature Med 6:719–720PubMedCrossRefGoogle Scholar
  90. 88.
    Marcus DM (1960) A study of the mechanism of the anticomplementary activity of γ-globulin. J Immunol 84:273–284PubMedGoogle Scholar
  91. 89.
    Maring JA, MacAuley C, Theisen PW, Dunston B, Stefanisko K, Adams EJ, Rentsch M, Rohwer RG, Morgenthaler JJ (1998) An-/Abreicherung von TSE-Infektiösität während der Plasmafraktionierung. Infusionstherapie und Transfusionsmedizin 25:85Google Scholar
  92. 90.
    Mast AE, Stadanlick JE, Lockett JM, Dietzen DJ (1999) Solvent/detergent-treated plasma has decreased antitrypsin activity and absent antiplasmin activity. Blood 94:3922–3927PubMedGoogle Scholar
  93. 91.
    Matsumoto A, Yeo AE, Shih JW, Tanaka E, Kiyosawa K, Alter HJ (1999) Transfusion-associated TT virus infection and its relationship to liver disease. Hepatology 30:283–288Google Scholar
  94. 92.
    Munoz SJ, Alter HJ, Nakatsuji Y, Shih JW, Reddy RK, Jeffers L, Schiff ER, Reid AE, Marrone A, Rothstein K, Manzarbeitia C, Liang TJ (1999) The significance of hepatitis G virus in serum of patients with sporadic fulminant and subfulminant hepatitis of unknown etiology. Blood 94:1460–1464PubMedGoogle Scholar
  95. 93.
    Nakamura Y, Aso E, Yanagawa H (1999) Relative risk of Creutzfeldt-Jakob disease with cadaveric dura transplantation in Japan. Neurology 53:218–220PubMedGoogle Scholar
  96. 94.
    Newland AC, Macey MG, Veys PA (1989) Cellular changes during the infusion of high dose intravenous immunoglobulin. Blut 59:82–87PubMedCrossRefGoogle Scholar
  97. 95.
    Ng PK, O’Rourke PE, Andersen JD, Tsay GC, Dobkin MB (1993) Process-scale purification of immunoglobulin M concentrate. Vox Sang 65:81–86PubMedCrossRefGoogle Scholar
  98. 96.
    Niel C, de Oliveira JM, Ross RS, Gomes SA, Roggendorf M, Viazov S (1999) High prevalence of TT virus infection in Brazilian blood donors. J Med Virol 57:259–263PubMedCrossRefGoogle Scholar
  99. 97.
    Nishizawa T, Okamoto H, Konishi K, Yoshizawa H, Miyakawa Y, Mayumi M (1997) A novel DNA virus (TTV) associated with elevated transaminase levels in posttransfusion hepatitis of unknown etiology. Biochem Biophys Res Commun 241:92–97PubMedCrossRefGoogle Scholar
  100. 98.
    Nitschmann H, Kistler P, Lergier W (1954) Vereinfachtes Verfahren zur Gewinnung von humanem Albumin und Gamma-Globulin aus Blutplasma mittels Alkoholfällung. Helv chim Acta 37:866–873CrossRefGoogle Scholar
  101. 99.
    Nübling CM, Gröner A, Löwer J (1998) GB virus C/hepatitis G virus and intravenous immunoglobulins. Vox Sang 75:189–192PubMedCrossRefGoogle Scholar
  102. 100.
    Nübling CM, Löwer J (1996) GB-C genomes in a high-risk group, in plasma pools, and in intravenous immunoglobulin. Lancet 347:68–68PubMedCrossRefGoogle Scholar
  103. 101.
    Oncley JL, Melin M, Richert DA, Cameron JW, Gross PM (1949) The separation of the antibodies, isoagglutinins, prothrombin, plasminogen and β1 -lipoprotein into sub fractions of human plasma. J Am Chem Soc 71:541–550PubMedCrossRefGoogle Scholar
  104. 102.
    Oomes PG, van der Meché FG, Kleyweg RP and the Dutch Guillain-Barré Study Group (1996) Liver function disturbances in Guillain-Barré syndrome: a prospective longitudinal study in 100 patients. Neurology 46:96–100PubMedGoogle Scholar
  105. 103.
    Painter RH, Law DT (1984) Structural and biological properties of three intravenous immunoglobulin preparations. In: Waters AH, Webster AD (eds) Intravenous immunoglobulins in immunodeficiency syndromes and idiopathic thrombocytopenic purpura. Royal Society of Medicine, London, pp 11–18Google Scholar
  106. 104.
    Parfentjew IA (1936) Method for purification of antitoxins and the like. United States Patent Office No. 2,065,196, pp 1–11Google Scholar
  107. 105.
    Parfentjew IA (1938) Treatment of antitoxins and the like. United States Patent Office No. 2,123,198, pp 1–9Google Scholar
  108. 106.
    Patry D, Curry B, Easton D, Mastrianni JA, Hogan DB (1998) Creutzfeldt-Jakob disease (CJD) after blood product transfusion from a donor with CJD. Neurology 50:1872–1873PubMedGoogle Scholar
  109. 107.
    Pavlova BG, Heinz R, Selim U, Tuchler H, Pittermann E, Eder G (1999) Association of GB virus C (GBV-C)/hepatitis G virus (HGV) with haematological diseases of different malignant potential. J Med Virol 57:361–366PubMedCrossRefGoogle Scholar
  110. 108.
    Petermann ML, Pappenheimer AM (1941) The ultracentrifugal analysis of diphtheria proteins. J Phys Chem 45:1CrossRefGoogle Scholar
  111. 109.
    Pisani G, Cristiano K, Wirz M, Bisso G, Beneduce F, Morace G, Rapicetta M, Gentili G (1999) Prevalence of TT virus in plasma pools and blood products. Br J Haematol 106:431–435PubMedCrossRefGoogle Scholar
  112. 110.
    Pope CG (1938) Disaggregation of protein by enzymes. Br J Exp Path 19: 245–251Google Scholar
  113. 111.
    Porter RR (1950) The formation of a specific inhibitor by hydrolysis of rabbit antiovalbumin. Biochem J 46:479PubMedGoogle Scholar
  114. 112.
    Porter RR (1973) Structural studies of immunoglobulins. Science 180:713–716PubMedCrossRefGoogle Scholar
  115. 113.
    Prati D, Lin YH, De Mattei C, Liu JK, Farma E, Ramaswamy L, Zanella A, Lee H, Rebulla P, Allain JP, Sirchia G, Chen B (1999) A prospective study on TT virus infection in transfusion-dependent patients with β-thalassemia. Blood 93: 1502–1505PubMedGoogle Scholar
  116. 114.
    Ratko TA, Burnett DA, Foulke GE, Matuszewski KA, Sacher RA, Ehmann WC, Givner LB, Kahaleh B, Samaha FJ, Siegel J, Wingard JR, Wordell CJ, Yocum DE (1995) Recommendations for off-label use of intravenously administered immunoglobulin preparations. JAMA 273:1865–1870PubMedCrossRefGoogle Scholar
  117. 115.
    Roux KH, Tankersley DL (1990) A view of the human idiotypic repertoire -Electron microscopic and immunologic analyses of spontaneous idiotype-anti-idiotype dimers in pooled human IgG. J Immunol. 144:1387–1395PubMedGoogle Scholar
  118. 116.
    Rylatt DB, Napoli M, Ogle D, Gilbert A, Lim S, Nair CH (1999) Electrophoretic transfer of proteins across Polyacrylamide membranes. J Chromatogr A 865:145–153PubMedCrossRefGoogle Scholar
  119. 117.
    Saldanha J, Minor P (1996) Detection of human parvovirus B19 DNA in plasma pools and blood products derived from these pools: implications for efficiency and consistency of removal of B19 DNA during manufacture. Br J Haematol 93:714–719PubMedCrossRefGoogle Scholar
  120. 118.
    Schnorf J, Arnet B, Burek-Kozlowska A, Gennari K, Rohner R, Späth PJ, Spycher MO (1996) Laboratory parameters meaured during infusion of immunoglobulin preparations for intravenous use and related tolerability. In: Kazatchkine MD, Morell A (eds) Intravenous immunoglobulin — research and therapy. The Parthenon Publishing Group, London, pp 312–313Google Scholar
  121. 119.
    Schroeder DD, Tankersley DL, Lundblad JL (1981) A new preparation of modified immune serum globulin (human) suitable for intravenous administration. 1. Standardization of the reduction and alkylation reaction. Vox Sang 40:373–382PubMedCrossRefGoogle Scholar
  122. 120.
    Schroeder DD, Tankersley DL, Lundblad JL (1981) A new preparation of modified serum globulin (human) suitable for intravenous administration. 2. Functional characterization. Vox Sang 40:383–394PubMedCrossRefGoogle Scholar
  123. 121.
    Schultze HE, Schwick G (1962) Über neue Möglichkeiten intravenöser Gammaglobulin-Applikation. Dt Med Wochenschr 87:1643–1650CrossRefGoogle Scholar
  124. 122.
    Seifried E, Roth WK (2000) First Statistical survey of HCV, HBV, HIV-1 NAT screening of blood donors in the red cross blood serivce centers in Germany. Vox Sang 78 (suppl 1): oral 080Google Scholar
  125. 123.
    Shev S, Björkman P, Norkrans G, Foberg U, Frydén A, Lindh G, Lindholm A, Weiland O, Widell A (1998) GBV-C/HGV infection in hepatitis C virus-infected deferred Swedish blood donors. J Med Virol 54:75–79PubMedCrossRefGoogle Scholar
  126. 124.
    Sorensen PS, Wanscher B, Jensen CV, Schreiber K, Blinkenberg M, Ravnborg M, Kirsmeier H, Larsen VA, Lee ML (1998) Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 50:1273–1281PubMedGoogle Scholar
  127. 125.
    Späth P, Kempf C (2000) Herstellung von intravenös verabreichbaren Immunglobulinen und Virussicherheit. In: Wahn V (Hrsg) Klinischer Einsatz von intravenösen Immunglobulinen. Unimed, Bremen, S 21–35Google Scholar
  128. 126.
    Stampfli K, Spengler GA, Barandun S, Riva G (1959) Die Therapie bakterieller Infektionen mit γ-Globulin-Präparaten. Helv Med Acta 26:424–460PubMedGoogle Scholar
  129. 127.
    Steg RE, Lefkowitz DM (1994) Cerebral infarction following intravenous immu-noglobuilin therapy for myasthenia gravis. Neurology 44:1180–1181PubMedGoogle Scholar
  130. 128.
    Steinbuch M (1980) Protein fractionation by ammonium sulfate, Rivanol and ca-prylic acid precipitation. In: Curling JM (ed) Methods of plasma protein fractionation. Academic Press, London, pp 33–56Google Scholar
  131. 129.
    Steinhardt B (1998) Blood plasma safety — plasma product risks are low if good manufacturing practices are followed. GAO — United States General Accounting Office 98:1–45Google Scholar
  132. 130.
    Stephan W (1969) Beseitigung der Komplementfixierung von Gamma-Globulin durch chemische Modifizierung mit β-Propiolacton. Z Klin Chem Klin Biochem 7:282–286PubMedGoogle Scholar
  133. 131.
    Stucki M, Moudry R, Kempf C, Omar A, Schlegel A, Lerch PG (1997) Characterisation of a chromatographically produced anti-D immunoglobulin product. J Chromatogr B Biomed Sci Appl 700:241–248PubMedCrossRefGoogle Scholar
  134. 132.
    Tagger A, Donato F, Ribero ML, Binelli G, Gelatti U, Portera G, Albertini A, Fasola M, Chiesa R, Nardi G (1999) A case-control study on a novel DNA virus (TT virus) infection and hepatocellular carcinoma. The Brescia HCC Study. He-patology 30:294–299Google Scholar
  135. 133.
    Tarn DA, Morton LD, Stroncek DF, Leshner RT (1996) Neutropenia in a patient receiving intravenous immune globulin. J Neuroimmunol 64:175–178CrossRefGoogle Scholar
  136. 134.
    Tan E, Hajinazarian M, Bay W, Neff J, Mendell JR (1993) Acute renal failure resulting from intravenous immunoglobulin therapy. Arch Neurol 50:137–139PubMedCrossRefGoogle Scholar
  137. 135.
    Tankersley DL (1994) Dimer formation in immunoglobulin preparations and speculations on the mechanism of action of intravenous immune globulin in autoimmune disease. Immunol Rev 139:159–172PubMedCrossRefGoogle Scholar
  138. 136.
    Taranta A, Franklin EC (1961) Complement fixation by antibody fragments. Science 134:1981–1982PubMedCrossRefGoogle Scholar
  139. 137.
    Turner ML, Ironside JW (1998) New-variant Creutzfeldt-Jakob disease: the risk of transmission by blood transfusion. Blood Rev 12:255–268PubMedCrossRefGoogle Scholar
  140. 138.
    Voltz R, Rosen FV, Yousry T, Beck J, Hohlfeld R (1996) Reversible encephalopathy with cerebral vasospasm in a Guillain-Barré syndrome patient treated with intravenous immunoglobulin. Neurology 46:250–251PubMedGoogle Scholar
  141. 139.
    Whittam LR, Hay RJ, Hughes RAC (1997) Eczematous reactions to human immune globulin. Br J Dermatol 137:481–482PubMedCrossRefGoogle Scholar
  142. 140.
    Widell A, Zhang YY, Andersson-Gare B, Hammarstrom L (1997) At least three hepatitis C virus strains implicated in Swedish and Danish patients with intravenous immunoglobulin-associated hepatitis C. Transfusion 37:313–320PubMedCrossRefGoogle Scholar
  143. 141.
    Will RG, Kimberlin RH (1998) Creutzfeldt-Jakob disease and the risk from blood or blood products. Vox Sang 75:178–180PubMedCrossRefGoogle Scholar
  144. 142.
    Williams PE, Yap PL, Gillon J, Grawford RJ, Urbaniak SJ, Galea G (1989) Transmission of Non-A, Non-B hepatitis by pH 4-treated intravenous immunoglobulin. Vox Sang 57:15–18PubMedCrossRefGoogle Scholar
  145. 143.
    Wilson K, Code C, Ricketts MN (2000) Risk of acquiring Creutzfeldt-Jakob disease from blood transfusions: systematic review of case-controlled studies. BMJ 321:17–19PubMedCrossRefGoogle Scholar
  146. 144.
    Wölfle J, Berg T, Keller KM, Schreier E, Lentze MJ (1998) Persistent hepatitis G virus infection after neonatal transfusion. J Pediatr Gastroenterol Nutr 26:402–407CrossRefGoogle Scholar
  147. 145.
    Wright JK, Tschopp J, Jaton JC, Engel J (1980) Dimeric, trimeric and tetrameric complexes of immunoglobulin G fix complement. Biochem J 187:775–780PubMedGoogle Scholar
  148. 146.
    Yap PL (1996) The viral safety of intravenous immune globulin. Clin Exp Immunol 104:35–42PubMedGoogle Scholar
  149. 147.
    Yokozaki S, Toyoda H, Nakano I, Katano Y, Ebata M, Fukuda Y, Takamatsu J, Saito H, Hayakawa T (1999) Infection with TT virus, a novel transfusion-transmissible DNA virus, in haemophiliacs and in blood products. Br J Haematol 105:1114–1119PubMedCrossRefGoogle Scholar
  150. 148.
    Yu MW, Mason BL, Guo ZP, Tankersley DL, Nedjar S, Mitchell FD, Biswas RM, Nübling CM, Willkommen H, Löwer J (1995) Hepatitis C transmission associated with intravenous immunoglobulins. Lancet 345:1173–1174PubMedCrossRefGoogle Scholar
  151. 149.
    Yu Z, Lennon VA (1999) Mechanism of intravenous immune globulin therapy in antibody-mediated autoimmune diseases. N Engl J Med 340:227–228PubMedCrossRefGoogle Scholar
  152. 150.
    Zuckerman AJ (1996) Alphabet of hepatitis viruses. Lancet 347:558–559PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2001

Authors and Affiliations

  • P. Späth
  • C. Kempf
  • R. Gold

There are no affiliations available

Personalised recommendations