Antibodies to gangliosides and galactocerebroside in patients with Guillain–Barré syndrome with preceding Campylobacter jejuni and other identical infections

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Abstract

The relationship between preceding infections and antibodies to glycolipids was investigated in 205 Japanese patients with Guillain–Barré syndrome (GBS). Serological evidence of recent Campylobacter jejuni (C. jejuni) infection was found in 45% of the patients, compared with 1% in healthy controls. In contrast, recent infection of cytomegalovirus (CMV), Mycoplasma pneumoniae (M. pneumoniae) and Epstein–Barr virus (EBV) was detected in only 5%, 2% and none of the patients, respectively. C. jejuni-associated GBS was more frequent in early spring than in other seasons. All stool specimens positive for C. jejuni isolation were obtained within 10 days after the onset of GBS symptoms. Of 13 C. jejuni isolates from GBS patients, 10 (77%) belonged to Penner serotype 19 (heat-stable, HS-19). Elevated titers of anti-GM1 antibody were found in 8 (80%) of 10 GBS patients whose C. jejuni isolates belonged to HS-19 and in none of those infected with non-HS-19 C. jejuni (P=0.04), and in 49% of 92 patients with C. jejuni infection and 25% of patients without infection of C. jejuni, CMV, EBV, or M. pneumoniae (P=0.0007). The frequencies of elevated antibody titers to GD1a, GD1b and GQ1b were also significantly higher in GBS patients associated with C. jejuni than those not associated with C. jejuni, CMV, EBV, and M. pneumoniae. GBS in Japan seems to be associated more frequently with C. jejuni and less frequently with CMV than in Europe and North America.

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.

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