Axonal Degeneration Induced by Intraneural Injection of Campylobacter jejuni Antiserum Containing High Titer Anti-GM1 Antibody

Abstract

Ganglioside-like structures in Campylobacter jejuni (C. jejuni) lipooligosaccharide (LOS) can induce antiganglioside antibodies, which might cause nerve damage. In this study, we injected the following three antisera directly into the sciatic nerve of guinea pigs, to investigate the role of anti-glycolipids antibody in inducing neural injury: (i) the wild strain antiserum, a mixture of the sera obtained from the guinea pigs immunized with C. jejuni wild-type strain (HS:19) that had a high titer anti-GM1 IgG antibody (range: 800-6,400; median: 2,400) and a high titer anti-LOS IgG antibody; (ii) the galE mutant antiserum, a mixture of the sera obtained from the guinea pigs immunized with the galE mutant strain that had only a high titer anti-LOS IgG antibody but no anti-GM1 antibody; and (iii) the control antiserum, a mixture of the sera obtained from the guinea pigs immunized with Freund's complete adjuvant alone which had no anti-GM1 or anti-LOS IgG antibody. Pathological examinations showed that the wild strain C. jejuni antiserum produced axonal degeneration in sciatic nerves. Demyelination was rare, and no inflammatory cells were present. The pathological features are consistent with those seen in human patients with axonal GBS. No such changes were observed in nerves injected with the galE mutant antiserum. The experiment showed that passive transfer of serum containing high titer GM1 antibody caused axonal degeneration of peripheral nerves. The result, which reproduced our previous findings in an active immunization study, therefore further confirmed the critical role of the anti-glycolipid antibody in the induction of neuropathy.

Key words

antibody - Campylobacter jejuni - galE gene - ganglioside - Guillain-Barré syndromes - lipooligosaccharide - mimicry - neuropathy

References

• 1 Ang CW, Klerk MA De, Endtz HP, Jacobs BC, Laman JD, Meché FGA van der. 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
• 2 Chowdhury D, Arora A. Axonal Guillain-Barré syndrome: a critical review.  Acta Neurol Scand. 2001;  103 267-277
• 3 Dyck PJ. Pathological alterations of the peripheral nerves. In: Dyck PJ, Thomas PK, Lambert E (Eds). Peripheral neuropathy. 3rd edn., Philadelphia: Saunders 1993: 536-542
• 4 Fry BN, Feng S, Chen YY, Newell DG, Coloe PJ, Korolik V. The galE gene of Campylobacter jejuni is involved in lipopolysaccharide synthesis and virulence.  Infect Immun. 2000;  68 2594-2601
• 5 Godschalk PCR, Heikema AP, Gilbert M, Komagamine T, Ang CW, Glerum J. et al . The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome.  J Clin Invest. 2004;  114 1659-1665
• 6 Griffin JW, Li CY, Macko C, Ho TW, Hsieh ST, Xue P. et al . Early nodal change in the acute motor axonal neuropathy pattern of the Guillain-Barré syndrome.  J Neurocytol. 1996;  25 33-51
• 7 Hafer-Macko C, Hsieh S-T, Li CY, Ho TW, Sheikh K, Cornblath DR. et al . Acute motor axonal neuropathy: an antibody-mediated attack on axolemma.  Ann Neurol. 1996;  40 635-644
• 8 Hughes RA, Cornblath CR. Guillain-Barré syndrome.  Lancet. 2005;  366 1653-1666
• 9 Paparounas K, O'Hanlon GM, O'Leary CP, Rowan EG, Willison HJ. 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
• 10 Phongsisay V, Perera VN, Fry BN. Exchange of lipooligosaccharide synthesis genes creates potential Guillain-Barré syndrome-inducible strains of Campylobacter jejuni.  Infect Immun. 2006;  74 1368-1372
• 11 Yu RK, Usuki S, Ariga T. Ganglioside molecular mimicry and its pathological roles in Guillain-Barré syndrome and related diseases.  Infect Immun. 2006;  74 6517-6527
• 12 Shu XM, Cai FC, Zhang XP. Carbohydrate mimicry of Campylobacter jejuni lipooligosaccharide is critical for the induction of anti-GM1 antibody and neuropathy.  Muscle Nerve. 2006;  33 225-231
• 13 Susuki K, Rasband MN, Tohyama K, Koibuchi K, Okamoto S, Funakoshi K. et al . Anti-GM1 antibodies cause complement-mediated disruption of sodium channel clusters in peripheral motor nerve fibers.  J Neurosci. 2007;  27 3956-3967
• 14 Waksman BH, Adams RD. Allergic neuritis: an experimental disease of rabbits induced by the injection of peripheral nervous tissue and adjuvants.  J Exp Med. 1955;  102 213-236
• 15 Willison HJ, Trapp BD, Bacher J, Dalakas M, Griffin JW, Quarles RH. Demyelination induced by intraneural injection of human anti-myelin-associated glycoprotein antibodies.  Muscle Nerve. 1988;  11 1169-1176
• 16 Willison HJ, Yuki N. Peripheral neuropathies and anti-glycolipid antibodies.  Brain. 2002;  125 2591-2625
• 17 Yuki N, Taki T, Inagaki F, Kasama T, Takahashi M, Saito K. et al . A bacterium lipopolysaccharide that elicits Guillain-Barré syndrome has a GM1 ganglioside-like structure.  J Exp Med. 1993;  178 1771-1775
• 18 Yuki N. Infectious origins of, and molecular mimicry in, Guillain-Barré and Fisher syndromes.  Lancet Infect Dis. 2001;  1 29-37
• 19 Yuki N, Susuki K, Koga M, Nishimoto Y, Odaka M, Hirata K. et al . Carbohydrate mimicry between human ganglioside GM1 and Campylobacter jejuni lipooligosaccharide causes Guillain-Barré syndrome.  Proc Natl Acad Sci USA. 2004;  101 11404-11409

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