Skip to main content
SpringerLink
Log in

Bedeutung intravenöser Immunglobuline zur Behandlung immunvermittelter Polyneuropathien

The significance of intravenous immunoglobulin in treatment of immune-mediated polyneuropathies

  • Übersichten
  • Published:
Der Nervenarzt Aims and scope Submit manuscript

Zusammenfassung

Die Langzeittherapie immunvermittelter Polyneuropathien ist nach wie vor eine Herausforderung. Bei der akut verlaufenden Polyneuritis, dem Guillain-Barré-Syndrom, gelten hochdosierte polyvalente intravenöse Immunglobuline (IVIG) als etablierte Therapieoption. Eine unlängst publizierte randomisierte, placebokontrollierte Studie bei Patienten mit chronisch entzündlicher demyelinisierender Polyradikuloneuropathie (CIDP) zeigte, dass IVIG auch bei dieser Krankheitsentität sowohl kurz- als auch langfristig klinisch wirksam sind und dabei eine gute Verträglichkeit aufweisen.

In dieser Übersichtsarbeit sollen die Daten dieser so genannten ICE-Studie („Intravenous immune globulin for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy study“) dargestellt sowie der Stellenwert von IVIG zur Behandlung immunvermittelter Polyneuropathien diskutiert werden.

Summary

Long-term treatment of immune-mediated polyneuropathies remains difficult. For acute polyneuritis, or Guillain-Barré syndrome, the established standard therapy utilizes high doses of polyvalent intravenous immunoglobulins (IVIG). A recently published randomized placebo-controlled study of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) showed IVIG to be clinically effective also for this disorder in both short and long term. This survey presents data of this so-called ICE study (“Intravenous immune globulin for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy”). It also discusses the value of IVIG in the treatment of immune-mediated polyneuropathies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Kieseier BC, Hartung HP, Wiendl H (2006) Immune circuitry in the peripheral nervous system. Curr Opin Neurol 19:437–445

    Article  PubMed  CAS  Google Scholar 

  2. Meyer zu Horste G, Hu W, Hartung HP et al (2008) The immunocompetence of schwann cells. Muscle Nerve 37:3–13

    Article  CAS  Google Scholar 

  3. Kieseier BC, Wiendl H, Hartung HP (2006) The inflamed peripheral nervous system: update on immune therapies. Curr Opin Neurol 19:433–436

    Article  PubMed  CAS  Google Scholar 

  4. Gold R, Kieseier BC (2006) Therapy of immune neuropathies with intravenous immunoglobulins. J Neurol 253:V59–V63

    Article  PubMed  CAS  Google Scholar 

  5. Meyer zu Horste G, Hartung HP, Kieseier BC (2007) From bench to bedside–experimental rationale for immune-specific therapies in the inflamed peripheral nerve. Nat Clin Pract Neurol 3:198–211

    Article  CAS  Google Scholar 

  6. Mäurer M, Gold R (2002) Animal models of immune-mediated neuropathies. Curr Opin Neurol 15:617–622

    Article  PubMed  Google Scholar 

  7. Bosboom WM, Van den Berg LH, Mollee I et al (2001) Sural nerve T-cell receptor Vbeta gene utilization in chronic inflammatory demyelinating polyneuropathy and vasculitic neuropathy. Neurology 56:74–81

    PubMed  CAS  Google Scholar 

  8. Illes Z, Kondo T, Newcombe J et al (2000) Differential expression of NK T cell V alpha 24J alpha Q invariant TCR chain in the lesions of multiple sclerosis and chronic inflammatory demyelinating polyneuropathy. J Immunol 164:4375–4381

    PubMed  CAS  Google Scholar 

  9. Schmidt B, Toyka KV, Kiefer R et al (1996) Inflammatory infiltrates in sural nerve biopsies in Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Muscle Nerve 19:474–487

    Article  PubMed  CAS  Google Scholar 

  10. Winer J, Hughes S, Cooper J et al (2002) gammadelta T cells infiltrating sensory nerve biopsies from patients with inflammatory neuropathy. J Neurol 249:616–621

    Article  PubMed  Google Scholar 

  11. Illes Z, Shimamura M, Newcombe J et al (2004) Accumulation of Valpha7.2-Jalpha33 invariant T cells in human autoimmune inflammatory lesions in the nervous system. Int Immunol 16:223–230

    Article  PubMed  CAS  Google Scholar 

  12. Koga M, Yuki N, Tsukada Y et al (2003) CDR3 spectratyping analysis of the T cell receptor repertoire in Guillain-Barre and Fisher syndromes. J Neuroimmunol 141:112–117

    Article  PubMed  CAS  Google Scholar 

  13. Gold R, Archelos JJ, Hartung H-P (1999) Mechanisms of immune regulation in the peripheral nervous system. Brain Pathol 9:343–360

    PubMed  CAS  Google Scholar 

  14. Griffin JW, George R, Ho T (1993) Macrophage systems in peripheral nerves. A review. J Neuropathol Exp Neurol 52:553–560

    Article  PubMed  CAS  Google Scholar 

  15. Kiefer R, Kieseier BC, Stoll G et al (2001) The role of macrophages in immune-mediated damage to the peripheral nervous system. Prog Neurobiol 64:109–127

    Article  PubMed  CAS  Google Scholar 

  16. Kieseier BC, Kiefer R, Gold R et al (2004) Advances in understanding and treatment of immune-mediated disorders of the peripheral nervous system. Muscle Nerve 30:131–156

    Article  PubMed  CAS  Google Scholar 

  17. Willison HJ, Yuki N (2002) Peripheral neuropathies and anti-glycolipid antibodies. Brain 125:2591–2625

    Article  PubMed  Google Scholar 

  18. Yuki N, Susuki K, Koga M et al (2004) Carbohydrate mimicry between human ganglioside GM1 and campylobacter jejuni lipooligosaccharide causes Guillain-Barre syndrome. Proc Natl Acad Sci U S A 101:11404–11409

    Article  PubMed  CAS  Google Scholar 

  19. Yuki N, Yamada M, Koga M et al (2001) Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 ganliosides. Ann Neurol 49:712–720

    Article  PubMed  CAS  Google Scholar 

  20. Hartung H-P, Willison H, Kieseier BC (2002) Acute immunoinflammatory neuropathy: Update on Guillain-Barré Syndrome. Curr Opin Neurol 15:571–577

    Article  PubMed  Google Scholar 

  21. Halstead SK, Zitman FM, Humphreys PD et al (2008) Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain 131:1197–1208

    Article  PubMed  Google Scholar 

  22. Jacobs BC, O’Hanlon GM, Bullens RW et al (2003) Immunoglobulins inhibit pathophysiological effects of anti-GQ1b-positive sera at motor nerve terminals through inhibition of antibody binding. Brain 126:2220–2234

    Article  PubMed  Google Scholar 

  23. Buchwald B, Weishaupt A, Toyka KV et al (1998) Pre- and postsynaptic blockade of neuromuscular transmission by Miller-Fisher syndrome IgG at mouse motor nerve terminals. Eur J Neurosci 10:281–290

    Article  PubMed  CAS  Google Scholar 

  24. Dilley A, Gregson NA, Hadden RD et al (2003) Effects on axonal conduction of anti-ganglioside sera and sera from patients with Guillain-Barre syndrome. J Neuroimmunol 139:133–140

    Article  PubMed  CAS  Google Scholar 

  25. Krampfl K, Mohammadi B, Buchwald B et al (2003) IgG from patients with Guillain-Barre syndrome interact with nicotinic acetylcholine receptor channels. Muscle Nerve 27:435–441

    Article  PubMed  CAS  Google Scholar 

  26. Katz U, Achiron A, Sherer Y et al (2007) Safety of intravenous immunoglobulin (IVIG) therapy. Autoimmun Rev 6:257–259

    Article  PubMed  CAS  Google Scholar 

  27. Dalakas MC (1997) Intravenous immune globulin therapy for neurologic diseases. Ann Intern Med 126:721–730

    PubMed  CAS  Google Scholar 

  28. Gold R, Stangel M, Dalakas MC (2007) Drug Insight: the use of intravenous immunoglobulin in neurology–therapeutic considerations and practical issues. Nat Clin Pract Neurol 3:36–44

    Article  PubMed  CAS  Google Scholar 

  29. Siberil S, SriRamulu E, Vir-Singh N et al (2007) Intravenous immunoglobulin in autoimmune and inflammatory diseases: more than mere transfer of antibodies. Transfus Apher Sci 37:103–107

    Article  PubMed  Google Scholar 

  30. Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313(5787):670–673

    Article  PubMed  CAS  Google Scholar 

  31. Bruhns P, Samuelsson A, Pollard JW, Ravetch JV (2003) Colony-stimulating factor-1-dependent macrophages are responsible for IVIG protection in antibody-induced autoimmune disease. Immunity 18:573–581

    Article  PubMed  CAS  Google Scholar 

  32. Nimmerjahn F, Ravetch JV (2008) Anti-inflammatory actions of intravenous immunoglobulin. Annu Rev Immunol 26:513–533 Review

    Article  PubMed  CAS  Google Scholar 

  33. Bril V, Ilse WK, Pearce R et al (1996) Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain-Barre syndrome. Neurology 46:100–103

    PubMed  CAS  Google Scholar 

  34. Plasma, Exchange/Sandoglobulin, Guillain-Barré et al (1997) Randomised trial of plasma exchange, intravenous immuoglobulin and combined treatments in Guillain-Barré syndrome. Lancet 349:225–230

    Article  Google Scholar 

  35. van der Meché FG, Schmitz PI (1992) A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barre syndrome. Dutch Guillain-Barre Study Group. N Engl J Med 326:1123–1129

    Article  Google Scholar 

  36. Diener HC, Haupt WF, Kloss TM et al (2001) A preliminary, randomized, multicenter study comparing intravenous immunoglobulin, plasma exchange and immune adsorption in Guillain-Barre syndrome. Eur Neurol 46:107–109

    Article  PubMed  CAS  Google Scholar 

  37. Hosokawa T, Hamaguchi K, Tomioka R et al (1998) Comparative study of efficacy of plasma exchange versus intravenous gammaglobulin treatment on acute postinfectious polyradiculoneuropathy: a preliminary report. Ther Apher Dial 2:288–291

    Article  CAS  Google Scholar 

  38. Hughes RA, Swan AV, Raphael JC et al (2007) Immunotherapy for Guillain-Barre syndrome: a systematic review. Brain 130:2245–2257

    Article  PubMed  Google Scholar 

  39. Imbach P, Barandun S, d’Apuzzo V et al (1981) High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood. Lancet 1:1228–1231

    Article  PubMed  CAS  Google Scholar 

  40. Raphael JC, Chevret S, Harboun M et al (2001) Intravenous immune globulins in patients with Guillain-Barre syndrome and contraindications to plasma exchange: 3 days versus 6 days. J Neurol Neurosurg Psychiatry 71:235–238

    Article  PubMed  CAS  Google Scholar 

  41. Korinthenberg R, Schessl J, Kirschner J et al (2005) Intravenously administered immunoglobulin in the treatment of childhood Guillain-Barre syndrome: a randomized trial. Pediatrics 116:8–14

    Article  PubMed  Google Scholar 

  42. Visser LH, Van der Meche FG, Van Doorn PA et al (1995) Guillain-Barre syndrome without sensory loss (acute motor neuropathy). A subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barre Study Group. Brain 118:841–847

    Article  PubMed  Google Scholar 

  43. Yuki N, Ang CW, Koga M et al (2000) Clinical features and response to treatment in Guillain-Barre syndrome associated with antibodies to GM1b ganglioside. Ann Neurol 47:314–321

    Article  PubMed  CAS  Google Scholar 

  44. Jacobs BC, van Doorn PA, Schmitz PI et al (1996) Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barre syndrome. Ann Neurol 40:181–187

    Article  PubMed  CAS  Google Scholar 

  45. Hadden RD, Karch H, Hartung HP et al (2001) Preceding infections, immune factors and outcome in Guillain-Barre syndrome. Neurology 56:758–765

    PubMed  CAS  Google Scholar 

  46. van Koningsveld R, Schmitz PI, Meche FG et al (2004) Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barre syndrome: randomised trial. Lancet 363:192–196

    Article  CAS  Google Scholar 

  47. Stangel M, Gold R, Einsatz von i.v (2004) Immunglobulinen in der Neurologie. Nervenarzt 75:801–815

    Article  PubMed  CAS  Google Scholar 

  48. Linker RA, Gold R (2008) Use of intravenous immunoglobulin and plasma exchange in neurological disease. Curr Opin Neurol 21:358–365

    Article  PubMed  CAS  Google Scholar 

  49. Köller H, Kieseier BC, Jander S, Hartung HP (2005) Chronic inflammatory demyelinating polyneuropathy. N Engl J Med 352:1343–1356

    Article  PubMed  Google Scholar 

  50. Doorn P van, Brand A, Strengers P et al (1990) High-dose intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy: a double-blind, placebo-controlled, crossover study. Neurology 40:209–212

    PubMed  Google Scholar 

  51. Hahn AF, Bolton CF, Zochodne D et al (1996) Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study. Brain 119:1067–1077

    Article  PubMed  Google Scholar 

  52. Cornblath DR, Chaudry V, Griffin JW (1991) Treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulin. Ann Neurol 30:104–106

    Article  PubMed  CAS  Google Scholar 

  53. Schaik IN van, Winer JB, Haan R de et al (2002) Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy: a systematic review. Lancet Neurol 1:491–498

    Article  PubMed  Google Scholar 

  54. Hahn AF, Bolton CF, Pillay N et al (1996) Plasma-exchange therapy in chronic inflammatory demyelinating polyneuropathy. A double-blind, sham-controlled, cross-over study. Brain 119(Pt 4):1055–1066

    Article  PubMed  Google Scholar 

  55. Mendell JR, J BR, Freimer ML et al (2001) Randomized controlled trial of IVIg in untreated chronic inflammatory demeylinating polyradiculoneuropathy. Neurology 56:445–449

    PubMed  CAS  Google Scholar 

  56. Hughes R, Bensa S, Willison H et al (2001) Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculopathy. Ann Neurol 50:195–201

    Article  PubMed  CAS  Google Scholar 

  57. European Federation of Neurological Societies, Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy (2005) Report of a joint task force of the European federation of neurological societies and the peripheral nerve society. J Peripher Nerv Syst 10:220–228

    Article  Google Scholar 

  58. Hughes RA, Donofrio P, Bril V et al (2008) Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebo-controlled trial. Lancet Neurol 7:136–144

    Article  PubMed  CAS  Google Scholar 

  59. Sander HW, Latov N (2003) Research criteria for defining patients with CIDP. Neurology 60:S8–S15

    PubMed  Google Scholar 

  60. Vermeulen M (2008) Intravenous immunoglobulin: a first-line treatment in CIDP? Lancet Neurol 7:115–116

    Article  PubMed  Google Scholar 

  61. Vermeulen M, Doorn PA van, Brand A et al (1993) Intravenous immunoglobulin treatment in patients with chronic inflammatory demyelinating polyneuropathy: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry 56:36–39

    Article  PubMed  CAS  Google Scholar 

  62. Thompson N, Choudhary P, Hughes RA, Quinlivan RM (1996) A novel trial design to study the effect of intravenous immunoglobulin in chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol 243:280–285

    Article  PubMed  CAS  Google Scholar 

  63. Asseldonk JT Van, Franssen H, Berg-Vos RM Van den et al (2005) Multifocal motor neuropathy. Lancet Neurol 4:309–319

    Article  PubMed  Google Scholar 

  64. Azulay JP, Blin O, Pouget J et al (1994) Intravenous immunoglobulin treatment in patients with motor neuron syndromes associated with anti-GM1 antibodies: a double-blind, placebo-controlled study. Neurology 44:429–432

    PubMed  CAS  Google Scholar 

  65. Federico P, Zochodne DW, Hahn AF et al (2000) Multifocal motor neuropathy improved by IVIg: randomized, double-blind, placebo-controlled study. Neurology 55:1256–1262

    PubMed  CAS  Google Scholar 

  66. Leger JM, Chassande B, Musset L et al (2001) Intravenous immunoglobulin therapy in multifocal motor neuropathy: a double-blind, placebo-controlled study. Brain 124:145–153

    Article  PubMed  CAS  Google Scholar 

  67. Berg LH Van den, Kerkhoff H, Oey PL et al (1995) Treatment of multifocal motor neuropathy with high dose intravenous immunoglobulins: a double blind, placebo controlled study. J Neurol Neurosurg Psychiatry 59:248–252

    Article  PubMed  Google Scholar 

  68. Berg-Vos RM Van den, Franssen H, Wokke JH et al (2000) Multifocal motor neuropathy: diagnostic criteria that predict the response to immunoglobulin treatment. Ann Neurol 48:919–926

    Article  PubMed  Google Scholar 

  69. Nobile-Orazio E, Cappellari A, Meucci N et al (2002) Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block. J Neurol Neurosurg Psychiatry 72:761–766

    Article  PubMed  CAS  Google Scholar 

  70. Ellis CM, Leary S, Payan J et al (1999) Use of human intravenous immunoglobulin in lower motor neuron syndromes. J Neurol Neurosurg Psychiatry 67:15–19

    Article  PubMed  CAS  Google Scholar 

  71. Joint Task Force of the EFNS and the PNS (2006) European federation of neurological societies / peripheral nerve society guideline on management of multifocal motor neuropathy. Report of a joint task force of the european federation of neurological societies and the peripheral nerve society. J Peripher Nerv Syst 11:1–8

    Article  Google Scholar 

  72. Leger JM, Viala K, Cancalon F et al (2008) Intravenous immunoglobulin as short- and long-term therapy of multifocal motor neuropathy: a retrospective study of response to IVIg and of its predictive criteria in 40 patients. J Neurol Neurosurg Psychiatry 79:93–96

    Article  PubMed  Google Scholar 

  73. Terenghi F, Cappellari A, Bersano A et al (2004) How long is IVIg effective in multifocal motor neuropathy? Neurology 62:666–668

    PubMed  CAS  Google Scholar 

  74. Lozeron P, Adams D (2007) Monoclonal gammopathy and neuropathy. Curr Opin Neurol 20:536–541

    PubMed  CAS  Google Scholar 

  75. Comi G, Roveri L, Swan A et al (2002) A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy. J Neurol 249:1370–1377

    Article  PubMed  CAS  Google Scholar 

  76. Gorson KC, Ropper AH, Weinberg DH et al (2002) Efficacy of intravenous immunoglobulin in patients with IgG monoclonal gammopathy and polyneuropathy. Arch Neurol 59:766–772

    Article  PubMed  Google Scholar 

  77. Joint Task Force of the EFNS and the PNS (2006) European Federation of Neurological Societies / Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a joint task force of the European federation of neurological societies and the peripheral nerve society. J Peripher Nerv Syst 11:9–19

    Article  Google Scholar 

  78. Kieseier BC, Meyer zu Hörste G, Lehmann HC et al (2008) Intravenous immunoglobulins in the treatment of immune neuropathies. Curr Opin Neurol (in press)

  79. Koller H, Schroeter M, Feischen H et al (2006) Subcutaneous self-infusions of immunoglobulins as a potential therapeutic regimen in immune-mediated neuropathies. J Neurol 253:1505–1506

    Article  PubMed  Google Scholar 

  80. Lee DH, Linker RA, Paulus W et al (2008) Subcutaneous immunoglobulin infusion: a new therapeutic option in chronic inflammatory demyelinating polyneuropathy. Muscle Nerve 37:406–409

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: Die Autoren erhielten in der Vergangenheit Vortrags- bzw. Beratungshonorare der Hersteller der im Artikel erwähnten Präparate (Baxter, CSL Behring, Biotest, Talecris).

Author information

Authors and Affiliations

  1. Klinik für Neurologie, Medizinische Hochschule Hannover, Hannover, Deutschland

    M. Stangel

  2. Neurologische Klinik, Heinrich-Heine-Universität Düsseldorf, Moorenstraße 5, 40225, Düsseldorf, Deutschland

    H.-P. Hartung &  B.C. Kieseier

  3. Abteilung Neurologie, St.-Josef-Hospital, Ruhr-Universität Bochum, Bochum, Deutschland

    R. Gold

Authors
  1. M. Stangel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H.-P. Hartung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B.C. Kieseier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to B.C. Kieseier.

Addendum

Addendum

Zwischenzeitlich publizierte eine italienische Arbeitsgruppe ihre Erfahrungen mit IVIG bei Patienten mit Diabetes mellitus und CIDP (CIDP-DM). 16 Patienten erhielten eine Erhaltungstherapie mit IVIG über einen Beobachtungszeitraum von mindestens 40 Monaten. Darunter kam es zu einer deutlichen Verbesserung und Stabilisierung des klinischen Befundes. Diese Ergebnisse unterstreichen ebenfalls die Wirksamkeit von IVIG als Therapie der CIDP.

Referenz: Jann S, Bramerio MA, Facchetti D, Sterzi R (2009) Intravenous immunoglobulin is effective in patients with diabetes and with chronic inflammatory demyelinating polyneuropathy: long term follow-up. J Neurol Neurosurg Psychiatry 80:70–73

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stangel, M., Hartung, HP., Gold, R. et al. Bedeutung intravenöser Immunglobuline zur Behandlung immunvermittelter Polyneuropathien. Nervenarzt 80, 678–687 (2009). https://doi.org/10.1007/s00115-008-2631-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00115-008-2631-y

Schlüsselwörter

Keywords

Search

Navigation