Antibodies to gangliosides and galactocerebroside in patients with Guillain–Barré syndrome with preceding Campylobacter jejuni and other identical infections
Introduction
Guillain–Barré syndrome (GBS) is an acute demyelinating paralytic disease of the peripheral nervous system. Although its cause and pathogenesis remain ill-defined, at least half of the reported cases of GBS have been preceded by clinical signs and symptoms of infection or other antecedent events during the few weeks before the neuropathy (Arnason and Soliven, 1993). Serological tests have implicated cytomegalovirus (CMV) and Epstein–Barr virus (EBV) more frequently than other viruses in patients with GBS in the United States and Europe (Dowling and Cook, 1981; Winer et al., 1988; Boucquey et al., 1991; Visser et al., 1996). An association of GBS with Mycoplasma pneumoniae (M. pneumoniae) infection was also reported (Goldschmidt et al., 1980). Campylobacter jejuni (C. jejuni) has recently been identified as a major cause of recent infections in GBS (Kaldor and Speed, 1984; Winer et al., 1988; Boucquey et al., 1991; Walsh et al., 1991; Enders et al., 1993; Gregson et al., 1993; Kuroki et al., 1993; Mishu et al., 1993; Vriesendorp et al., 1993; Rees et al., 1995b).
Elevated anti-ganglioside antibodies have been detected in some patients with GBS (Walsh et al., 1991; Ilyas et al., 1992; Nobile-Orazio et al., 1992; Enders et al., 1993; Simone et al., 1993; van den Berg et al., 1993; Vriesendorp et al., 1993). The frequency of anti-GM1 antibodies in different series of GBS patients varies from 2% or less to around 30%. The variable pattern and degree of antibody response observed in these patients could, at least in part, relate to the heterogeneity of sensitizing agents, since different bacteria or viruses may be involved in triggering an autoimmune attack against peripheral myelin or axon in GBS patients. Yuki et al. first described two Japanese patients after C. jejuni infection who developed acute motor axonal neuropathy and elevated anti-GM1 IgG antibody (Yuki et al., 1990). Compared with GBS described in Europe, the United States and Australia, axonal GBS seems to be more frequent in northern China (McKhann et al., 1993). Regional variation of the frequency of infectious agents, as well as racial differences in immunoregulatory genetic background could be the basis for the heterogeneity of clinical features of acute post-infectious neuropathy in different geographical areas or races.
In the present study, we determined the serum antibodies to GM1 and other glycolipids as well as to C. jejuni, CMV, EBV, and M. pneumoniae. We identified recent infection in a large group of 205 patients with GBS. There have been no reports which related the evidence of recent infection of various infectious agents to multiple serum glycolipids antibodies in a large group of GBS patients. We elucidated whether there is a correlation between presence of antibodies to glycolipids and various preceding infectious agents.
Section snippets
Patients
This study included 205 patients with GBS admitted to the hospitals in the greater Osaka–Kyoto–Kobe metropolitan area between 1990 and 1996. All the patients fulfilled the diagnostic criteria of Asbury et al. (1978).
Serum samples were obtained 1–27 days after the onset of GBS. Sera were stored at −80°C until tested.
Control serum samples for C. jejuni antibodies were collected from 100 healthy persons and 7 patients who had Salmonella enteritis. Control serum samples for CMV, EBV, M. pneumoniae
Frequencies of antibodies to C. jejuni
Ninety-two (45%) of 205 patients with GBS were found to have evidence of recent C. jejuni infection. Sixty (29%) patients had elevated antibody titers in two or more immunnoglobulin classes (criterion-1 in Table 1). Thirty-two (16%) patients showed either IgA or IgM antibody titers above 1:160 (criterion-2 in Table 1).
In 100 control serum samples, titer was 1:80 for IgA in two samples, 1:80 for IgM in two, and 1:320 for IgG in four. Out of those samples with positive antibody titer, one had
Preceding infection
We have identified the frequencies of recent infection of C. jejuni, CMV, EBV, and M. pneumoniae in 205 Japanese patients with GBS in the greater Osaka–Kyoto–Kobe metropolitan area between 1990 and 1996. Our serological data indicate that C. jejuni is the commonest infectious agent associated with GBS. Serological evidence of recent infection of C. jejuni was obtained in 45% of patients with GBS, but in only 1% of healthy controls, and the difference was highly significant (P=9.07×10−19).
Acknowledgements
We would like to thank Ms. E. Nisiguchi for her excellent technical assistance. This work was supported in part by a grant from the Neuroimmunological Research Committee, Ministry of Health and Welfare, Japan.
References (49)
- et al.
Clinical and serological studies in a series of 45 patients with Guillain–Barré syndrome
J. Neurol. Sci.
(1991) - et al.
Anti-GM1 IgA antibodies in Guillain–Barré syndrome
J. Neuroimmunol.
(1992) - et al.
Post-infection encephalitis with anti-galactocerebroside antibody subsequent to Mycoplasma pneumoniae infection
J. Neurol. Sci.
(1996) - et al.
Guillain–Barré syndrome associated with high titers of anti-GM1 antibodies
J. Neurol. Sci.
(1992) - et al.
Association between glycoconjugate antibodies and Campylobacter infection in patients with Guillain–Barré syndrome
J. Neuroimmunol.
(1991) - Arnason, B.G.W., Soliven, B., 1993. Acute inflammatory demyelinating polyradiculneuropathies. In: Dyck, P.J., Tohomas,...
- et al.
Criteria for diagnosis of Guillain–Barré syndrome
Ann. Neurol.
(1978) - et al.
Lipopolysaccharides from Camylobacter jejuni associated with Guillain–Barré syndrome patients mimic human gangliosides in structure
Infect. Immun.
(1994) - et al.
The Collaborative Diarrheal Disease Study Group: Campylobacter enteritis in United States: a multicenter study
Ann. Intern. Med.
(1983) - et al.
Role of infection in Guillain–Barré syndrome: laboratory confirmation of herpes viruses in 41 case
Ann. Neurol.
(1981)
The spectrum of immune responses to Campylobacter jejuni and glycoconjugates in Guillain–Barré syndrome and in other neuroimmunological disorders
Ann. Neurol.
Improved immunofluorescence antigens for detection of immunoglobulin M antibodies to Epstein–Barr viral capsid antigen and antibodies to Epstein–Barr virus nuclear antigen
J. Clin. Microbiol.
Mycoplasma antibody in Guillain–Barré syndrome and other neurological disorders
Ann. Neurol.
Antibodies to gangliosides in Guillain–Barré syndrome: specificity and relationship to clinical features Q
J. Med.
Serologic evidence of Campylobater jejuni/coli enteritis in patients with Guillain–Barré syndrome
Arch. Neurol.
Guillain–Barré syndrome in northern China; relationship to Campylobacter jejuni infection and anti-glycolipid antibodies
Brain
Campylobacter jejuni infections and anti-GM1 antibodies in Guillain–Barré syndrome
Ann. Neurol.
Guillain–Barré syndrome and Campylobacter jejuni: a serological study
Br. Med. J.
Guillain–Barré syndrome in the United States, 1978–1981: Additional observations from the national surveillance system
Neurology
Guillain–Barré syndrome associated with Camylobacter infection
Pediatr. Infect. Dis. J.
Campylobacter jejuni strains from patients with Guillain–Barré syndrome belong mostly to Penner serogroup 19 and contain β-N-acetylglucosamine residues
Ann. Neurol.
Anti-Gal-C antibodies in autoimmune neropathies subsequent to Mycoplasma infection
Muscle Nerve
Escherichia coli O157:H7: an emerging gastrointestinal pathogen: results of a one-year, prospective, population-based study
JAMA
Incidence of Campylobacter jejuni/coli from healthy people
Kansenshogaku Zasshi.
Cited by (90)
Quantification of Campylobacter jejuni contamination on chicken carcasses in France
2018, Food Research InternationalCitation Excerpt :This phenomenon is more accentuated in western countries with temperate climates (Jore et al., 2010; McCarthy et al., 2012; Strachan et al., 2013) than in Australia, New Zealand and countries with tropical climates (Mason et al., 2013; Spencer et al., 2012). Interestingly, seasonal patterns of GBS have been also described in Mexico (Nachamkin et al., 2007), China (McKhann et al., 1993), Argentina (Paradiso, Tripoli, Galicchio, & Fejerman, 1999), Curacao (van Koningsveld et al., 2001) and Japan (Hao et al., 1998). In our study, higher Campylobacter contamination goes beyond the summer period, it covers as well the autumn period (i.e. contamination higher from June to December than from January to May).
Clinical features in Guillain-Barré syndrome with anti-Gal-C antibody
2014, Journal of the Neurological SciencesCitation Excerpt :In contrast, a patient with axonal neuropathy and anti-Gal-C antibodies has also been reported [4]. The pathogenesis of GBS is thought to involve an autoimmune mechanism induced by infections [5,6], such as Campylobacter jejuni, cytomegalovirus and Mycoplasma pneumoniae (MP) [7,8]. Anti-glycolipid antibodies, probably produced by molecular mimicry, are considered an important factor in the pathogenesis of a subset of GBS.
Transverse Myelitis: Pathogenesis, Diagnosis, and Management
2010, Blue Books of NeurologyHeteromeric glycolipid complexes as modulators of autoantibody and lectin binding
2010, Progress in Lipid ResearchInnate and Adaptive Autoimmunity Directed to the Central Nervous System
2009, NeuronCitation Excerpt :Despite the attraction of these molecular similarities between microbes and components of the myelin sheath, no single microbe has been impugned in the pathogenesis of MS. In contrast, in the inflammatory polyneuropathy known as Guillain Barre syndrome, Campylobacter jejuni has been implicated as the trigger for acute axonal motor neuropathy, a type of inflammatory neuropathy resembling Guillain Barre. Campylobacter jejuni contains glycolipids that are also found in motor axons (Hao et al., 1998). Immune attack against these glycolipids triggers acute motor axon neuropathy.
European Academy of Neurology/Peripheral Nerve Society Guideline on diagnosis and treatment of Guillain–Barré syndrome
2023, European Journal of Neurology