Therapeutic Strategies in the Guillain-Barré Syndrome

ABSTRACT

The Guillain-Barré syndrome (GBS) represents the prototypic immune-mediated peripheral neuropathy, which is now recognized as a group of conditions with diverse pathology and pathogenesis. The observation that plasma exchange and intravenous immunoglobulin result in clinical improvement, the presence of circulating antibodies targeting structures on peripheral nerve tissue in sera from GBS patients, and the deposition of immunoglobulins and complement demonstrated on myelinated fibers in nerve biopsies from affected patients point to a critical role of the humoral immune response in the pathogenesis of GBS. However, the observation of inflammatory infiltrates in nerve and the critical pathogenic role of neuritogenic T lymphocytes as demonstrated in the animal model support the concept that a disordered cellular immunity is also of critical importance in the pathogenesis of this neuropathy. Current treatment strategies are aimed at mitigating the harmful effects of the immune system on peripheral nerve. This review will address the rationale for immunotherapy in GBS based on experimental and immunologic studies of the pathogenesis of this disease.

KEYWORDS

Guillain-Barré - syndrome - plasma exchange - intravenous immunoglobulins - molecular mimicry

REFERENCES

• 1 Govoni V, Granieri E. Epidemiology of the Guillain-Barré syndrome.  Curr Opin Neurol . 2001;  14 605-613
• 2 Hartung H-P, Pollard J D, Harvey G K, Toyka K V. Invited review: immunopathogenesis and treatment of the Guillain-Barré syndrome, part I and II.  Muscle Nerve . 1995;  18 137-164
• 3 Hahn A F. Guillain-Barré syndrome.  Lancet . 1998;  352 635-641
• 4 Hughes R AC. The concept and classification of Guillain-Barré syndrome and related disorders.  Rev Neurol (Paris) . 1995;  151 291-294
• 5 Van der Meche G F, Van Doorn A P, Meulstee J, Jennekens F G. Diagnostic and classification criteria for the Guillain-Barré syndrome.  Eur Neurol . 2001;  45 133-139
• 6 Willison H J, O'Hanlon G M. The immunopathogenesis of Miller Fisher syndrome.  J Neuroimmunol . 1999;  100 3-12
• 7 Winer J B. Guillain Barré syndrome.  Mol Pathol . 2001;  54 381-385
• 8 Hartung H-P, Willison H, Kieseier B C. Acute immunoinflammatory neuropathy: update on Guillain-Barré syndrome.  Curr Opin Neurol . 2002;  15 571-577
• 9 Griffin J W, Li C Y, Ho T W. et al . Guillain-Barré syndrome in northern China: the spectrum of neuropathological changes in clinically defined cases.  Brain . 1995;  118 577-595
• 10 Griffin J W, Li C Y, Ho T W. et al . Pathology of the motor-sensory axonal Guillain-Barré syndrome.  Ann Neurol . 1996;  39 17-28
• 11 Jacobs B C, Rothbarth P H, van der Meche G F. et al . The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.  Neurology . 1998;  51 1110-1115
• 12 Tsang R S. The relationship of Campylobacter jejuni infection and the development of Guillain-Barré syndrome.  Curr Opin Infect Dis . 2002;  15 221-228
• 13 Hadden R D, Karch H, Hartung H P. et al . Preceding infections, immune factors, and outcome in Guillain-Barré syndrome.  Neurology . 2001;  56 758-765
• 14 Gold R, Archelos J J, Hartung H P. Mechanisms of immune regulation in the peripheral nervous system.  Brain Pathol . 1999;  9 343-360
• 15 Yuki N. Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes.  Lancet Infect Dis . 2001;  1 29-37
• 16 Chiba A, Kusunoki S, Obata H, Machinami R, Kanazawa I. Serum anti-GQ1b IgG antibody is associated with ophthalmoplegia in Miller Fisher syndrome and Guillain-Barré syndrome: clinical and immunohistochemical studies.  Neurology . 1993;  43 1911-1917
• 17 O'Leary C P, Willison H J. The role of antiglycolipid antibodies in peripheral neuropathies.  Curr Opin Neurol . 2000;  13 583-588
• 18 Gabriel C M, Gregson N A, Hughes R A. Anti-PMP22 antibodies in patients with inflammatory neuropathy.  J Neuroimmunol . 2000;  104 139-146
• 19 Kwa M S, van Schaik N I, Brand A, Baas F, Vermeulen M. Investigation of serum response to PMP22, connexin 32 and P(0) in inflammatory neuropathies.  J Neuroimmunol . 2001;  116 220-225
• 20 Willison H J, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies.  Brain . 2002;  125 2591-2625
• 21 Koga M, Ang C W, Yuki N. et al . Comparative study of preceding Campylobacter jejuni infection in Guillain-Barré syndrome in Japan and The Netherlands.  J Neurol Neurosurg Psychiatry . 2001;  70 693-695
• 22 Ang C W, Koga M, Jacobs B C, Yuki N, van der Meche G F, van Doorn A P. Differential immune response to gangliosides in Guillain-Barré syndrome patients from Japan and The Netherlands.  J Neuroimmunol . 2001;  121 83-87
• 23 Ang C W, De Klerk A M, Endtz H P. et al . Guillain-Barré syndrome- and Miller Fisher syndrome-associated Campylobacter jejuni lipopolysaccharides induce anti-GM1 and anti-GQ1b Antibodies in rabbits.  Infect Immun . 2001;  69 2462-2469
• 24 Jacobs B C, van Doorn A P, Schmitz P IM. et al . Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome.  Ann Neurol . 1996;  40 181-187
• 25 Yuki N, Ang C W, Koga M. et al . Clinical features and response to treatment in Guillain-Barré syndrome associated with antibodies to GM1b ganglioside.  Ann Neurol . 2000;  47 314-321
• 26 Ogawara K, Kuwabara S, Mori M, Hattori T, Koga M, Yuki N. Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan.  Ann Neurol . 2000;  48 624-631
• 27 Hao Q, Saida T, Yoshino H, Kuroki S, Nukina M, Saida K. Anti-GalNAc-GD1a antibody-associated Guillain-Barré syndrome with a predominantly distal weakness without cranial nerve impairment and sensory disturbance.  Ann Neurol . 1999;  45 758-768
• 28 Yuki N, Yoshino H, Sato S, Miyatake T. Acute axonal polyneuropathy associated with anti-GM1 antibodies following Campylobacter enteritis.  Neurology . 1990;  40 1900-1902
• 29 Odaka M, Yuki N, Hirata K. Anti-GQ1b IgG antibody syndrome: clinical and immunological range.  J Neurol Neurosurg Psychiatry . 2001;  70 50-55
• 30 Yoshino H, Harukawa H, Asano A. IgG antiganglioside antibodies in Guillain-Barré syndrome with bulbar palsy.  J Neuroimmunol . 2000;  105 195-201
• 31 Koga M, Yuki N, Takahashi M, Saito K, Hirata K. Are Campylobacter curvus and Campylobacter upsaliensis antecedent infectious agents in Guillain-Barré and Fisher's syndromes?.  J Neurol Sci . 1999;  163 53-57
• 32 Gong Y, Tagawa Y, Lunn M P. et al . Localization of major gangliosides in the PNS: implications for immune neuropathies.  Brain . 2002;  125 2491-2506
• 33 Paparounas K, O'Hanlon G M, O'Leary C P, Rowan E G, Willison H J. Anti-ganglioside antibodies can bind peripheral nerve nodes of Ranvier and activate the complement cascade without inducing acute conduction block in vitro.  Brain . 1999;  122 807-816
• 34 Plomp J J, Molenaar P C, O'Hanlon G M. et al . Miller Fisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates.  Ann Neurol . 1999;  45 189-199
• 35 Goodyear C S, O'Hanlon G M, Plomp J J. et al . Monoclonal antibodies raised against Guillain-Barré syndrome-associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations.  J Clin Invest . 1999;  104 697-708
• 36 O'Hanlon G M, Plomp J J, Chakrabarti M. et al . Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal.  Brain . 2001;  124 893-906
• 37 Buchwald B, Weishaupt A, Toyka K V, Dudel J. Pre- and postsynaptic blockade of neuromuscular transmission by Miller-Fisher syndrome IgG at mouse motor nerve terminals.  Eur J Neurosci . 1998;  10 281-290
• 38 Plomp J J, Molenaar P C, O'Hanlon G M. et al . Miller Fisher anti-GQ1b antibodies: alpha-latrotoxin-like effects on motor end plates.  Ann Neurol . 1999;  45 189-199
• 39 Buchwald B, Bufler J, Carpo M. et al . Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome.  Neurology . 2001;  56 67-74
• 40 Kusunoki S, Shimizu J, Chiba A, Ugawa Y, Hitoshi S, Kanazawa I. Experimental sensory neuropathy induced by sensitization with ganglioside GD1b.  Ann Neurol . 1996;  39 424-431
• 41 Yuki N, Yamada M, Koga M. et al . Animal model of axonal Guillain-Barré syndrome induced by sensitization with GM1 gangliosides.  Ann Neurol . 2001;  49 712-720
• 42 Hadden R D, Gregson N A, Gold R, Willison H J, Hughes R A. Guillain-Barré syndrome serum and anti-Campylobacter antibody do not exacerbate experimental autoimmune neuritis.  J Neuroimmunol . 2001;  119 306-316
• 43 Gold R, Hartung H P, Toyka K V. Animal models for autoimmune demyelinating disorders of the nervous system.  Mol Med Today . 2000;  6 88-91
• 44 Khalili-Shirazi A, Gregson N A, Hall M A, Hughes R A, Lanchbury J S. T cell receptor V beta gene usage in Guillain-Barré syndrome.  J Neurol Sci . 1997;  145 169-176
• 45 Khalili-Shirazi A, Gregson N, Hughes R. CD1 expression in human peripheral nerve of GBS patients.  Biochem Soc Trans . 1997;  25 172S
• 46 Cooper J C, Ben-Smith A, Savage C O, Winer J B. Unusual T cell receptor phenotype V gene usage of gamma delta T cells in a line derived from the peripheral nerve of a patient with Guillain-Barré syndrome.  J Neurol Neurosurg Psychiatry . 2000;  69 522-524
• 47 Previtali S C, Feltri M L, Archelos J J, Quattrini A, Wrabetz L, Hartung H. Role of integrins in the peripheral nervous system.  Prog Neurobiol . 2001;  64 35-49
• 48 Previtali S C, Archelos J J, Hartung H P. Expression of integrins in experimental autoimmune neuritis and Guillain-Barré syndrome.  Ann Neurol . 1998;  44 611-621
• 49 Kieseier B C, Tani M, Mahad D. et al . Chemokines and chemokine receptors in inflammatory demyelinating neuropathies: a central role for IP-10.  Brain . 2002;  125 823-834
• 50 Kieseier B C, Kiefer R, Clements J M. et al . Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis.  Brain . 1998;  121 159-166
• 51 Mueller M, Wacker K, Ringelstein E B, Hickey W F, Imai Y, Kiefer R. Rapid response of identified resident endoneurial macrophages to nerve injury.  Am J Pathol . 2001;  159 2187-2197
• 52 Kiefer R, Kieseier B C, Stoll G, Hartung H-P. The role of macrophages in immune-mediated damage to the peripheral nervous system.  Prog Neurobiol . 2001;  64 109-127
• 53 Raphael J C, Chevret S, Hughes R A, Annane D. Plasma exchange for Guillain-Barré syndrome (Cochrane Review).  Cochrane Database Syst Rev . 2001;  2 CD001798
• 54 Hughes R A, Raphael J C, Swan A V, van Doorn A P. Intravenous immunoglobulin for Guillain-Barré syndrome (Cochrane Review).  Cochrane Database Syst Rev . 2001;  2 CD002063
• 55 Plasma Exchange/Sandoglobulin Guillain-Barré Syndrome Trial Group. Randomized trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome.  Lancet . 1997;  349 225-230
• 56 The Guillain-Barré Syndrome Study Group. Plasmapheresis and acute Guillain-Barré syndrome.  Neurology . 1985;  35 1096-1104
• 57 French Cooperative Group on Plasma Exchange in Guillain-Barré syndrome. Efficacy of plasma exchange in Guillain-Barré Syndrome.  Ann Neurol . 1987;  22 753-761
• 58 van der Meche G F, Schmitz P I. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain-Barré syndrome. Dutch Guillain-Barré Study Group.  N Engl J Med . 1992;  326 1123-1129
• 59 Bril V, Ilse W K, Pearce R, Dhanani A, Sutton D, Kong K. Pilot trial of immunoglobulin versus plasma exchange in patients with Guillain-Barré syndrome.  Neurology . 1996;  46 100-103
• 60 The French Cooperative Group on Plasma Exchange in Guillain-Barré Syndrome. Appropriate number of plasma exchanges in Guillain-Barré syndrome.  Ann Neurol . 1997;  41 298-306
• 61 Hughes R A, van Der Meche G F. Corticosteroids for treating Guillain-Barré syndrome.  Cochrane Database Syst Rev . 2000;  3 CD001446
• 62 Wollinsky K H, Hulser P J, Brinkmeier H. et al . CSF filtration is an effective treatment of Guillain-Barré syndrome: a randomized clinical trial.  Neurology . 2001;  57 774-780
• 63 Brinkmeier H, Aulkemeyer P, Wollinsky K H, Rudel R. An endogenous pentapeptide acting as a sodium channel blocker in inflammatory autoimmune disorders of the central nervous system.  Nat Med . 2000;  6 808-811
• 64 Feasby T E, Hartung H P. Drain the roots: a new treatment for Guillain-Barré syndrome?.  Neurology . 2001;  57 753-754
• 65 Raphael J C, Chevret S, Harboun M, Jars-Guincestre M C. Intravenous immune globulins in patients with Guillain-Barré syndrome and contraindications to plasma exchange: 3 days versus 6 days.  J Neurol Neurosurg Psychiatry . 2001;  71 235-238
• 66 Visser L H, Van der Meche G F, Van Doorn A P. et al . Guillain-Barré syndrome without sensory loss (acute motor neuropathy): a subgroup with specific clinical, electrodiagnostic and laboratory features. Dutch Guillain-Barré Study Group. Brain .  1995;  118 841-847
• 67 Jacobs BC, van Doorn A P, Schmitz P I. et al . Campylobacter jejuni infections and anti-GM1 antibodies in Guillain-Barré syndrome.  Ann Neurol . 1996;  40 181-187
• 68 Diegel M L, Rankin B M, Bolen J B, Dubois P M, Kiener P A. Cross-linking of Fc gamma receptor to surface immunoglobulin on B cells provides an inhibitory signal that closes the plasma membrane calcium channel.  J Biol Chem . 1994;  269 11409-11416
• 69 Kondo N, Kasahara K, Kameyama T. et al . Intravenous immunoglobulins suppress immunoglobulin productions by suppressing Ca(2+)-dependent signal transduction through Fc gamma receptors in B lymphocytes.  Scand J Immunol . 1994;  40 37-42
• 70 Lacroix-Desmazes S, Kaveri S V, Mouthon L. et al . Self-reactive antibodies (natural autoantibodies) in healthy individuals.  J Immunol Methods . 1998;  216 117-137
• 71 Lutz H U, Stammler P, Jelezarova E, Nater M, Spath P J. High doses of immunoglobulin G attenuate immune aggregate-mediated complement activation by enhancing physiologic cleavage of C3b in C3bn-IgG complexes.  Blood . 1996;  88 184-193
• 72 Imbach P, Barandun S, d'Apuzzo V. et al . High-dose intravenous gammaglobulin for idiopathic thrombocytopenic purpura in childhood.  Lancet . 1981;  1 1228-1231
• 73 Stangel M, Compston A. Polyclonal immunoglobulins (IVIg) modulate nitric oxide production and microglial functions in vitro via Fc receptors.  J Neuroimmunol . 2001;  112 63-71
• 74 Marchalonis J J, Kaymaz H, Dedeoglu F, Schluter S F, Yocum D E, Edmundson A B. Human autoantibodies reactive with synthetic autoantigens from T-cell receptor beta chain.  Proc Natl Acad Sci U S A . 1992;  89 3325-3329
• 75 Vassilev T L, Kazatchkine M D, Van Huyen P J. et al . Inhibition of cell adhesion by antibodies to Arg-Gly-Asp (RGD) in normal immunoglobulin for therapeutic use (intravenous immunoglobulin, IVIg).  Blood . 1999;  93 3624-3631
• 76 Viard I, Wehrli P, Bullani R. et al . Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.  Science . 1998;  282 490-493
• 77 Buchwald B, Ahangari R, Weishaupt A, Toyka K V. Intravenous immunoglobulins neutralize blocking antibodies in Guillain-Barré syndrome.  Ann Neurol . 2002;  51 673-680
• 78 Dalakas M C. Blockade of blocking antibodies in Guillain-Barré syndrome: "unblocking" the mystery of action of intravenous immunoglobulin.  Ann Neurol . 2002;  51 667-668
• 79 Créange A, Lerat H, Meyrignac C, Degos J-D, Gherardi R K, Cesaro P. Treatment of Guillain-Barré syndrome with interferon-b.  Lancet . 1998;  352 368-369
• 80 Schaller B, Radziwill A J, Steck A. Successful treatment of Guillain-Barré syndrome with combined administration of interferon-b-1a and intravenous immunoglobulin.  Eur Neurol . 2001;  46 167-168
• 81 Korn T, Toyka K, Hartung H P, Jung S. Suppression of experimental autoimmune neuritis by leflunomide.  Brain . 2001;  124 1791-1802
• 82 Kieseier B C, Krivacic K, Jung S. et al . Sequential expression of chemokines in experimental autoimmune neuritis.  J Neuroimmunol . 2000;  110 121-129
• 83 Archelos J J, Previtali S C, Hartung H P. The role of integrins in immune-mediated diseases of the nervous system.  Trends Neurosci . 1999;  22 30-38
• 84 Kieseier B C, Seifert T, Giovannoni G, Hartung H P. Matrix metalloproteinases in inflammatory demyelination: targets for treatment.  Neurology . 1999;  53 20-25
• 85 Bensa S, Hadden R D, Hahn A, Hughes R A, Willison H J. Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.  Eur J Neurol . 2000;  7 423-426