Autor(es): Feasby T E,Hughes R A

Resumo: Infections and vaccinations have long been known as frequent antecedents of GBS, but the special importance of the gastrointestinal pathogen Campylobacter jejuni was only first noticed in the early 1980s.3 The frequency of prior C. jejuni infection in GBS varies in different parts of the world, being 25% in a British and 45% in a Japanese study.4,5 An infection could trigger a neuropathic process such as GBS by direct infection of nerves (e.g., poliomyelitis or herpes zoster), production of a neurotoxin(e.g., diphtheria or botulism), or by triggering an immune response, either specific or nonspecific, which could then produce a secondary neuropathic effect. Indirect evidence for an immune mechanism in GBS includes the presence of lymphocytic infiltration of nerve and the ability of GBS serum to produce demyelination. The autoimmune experimental model of GBS, experimental allergic neuritis (EAN), is caused by a combination of T-cell-mediated immunity to myelin proteins and antibody to myelin glycolipids.6,7 The frequent occurrence of serum antiganglioside antibodies, especially anti-GM1, in GBS suggests the possibility of an antibody-mediated attack on nerve fibers in GBS.8,9 How might antiganglioside antibodies induce disease? Ganglioside GM1 has a wide distribution in the nervous system. Evidence from binding studies using cholera toxin and mostly nonhuman anti-GM1 antibodies suggests that this includes axonal membranes at the node and neuromuscular junction, and myelin, especially paranodally.10,11 Recent pathologic examinations of patients with both demyelinating and axonal forms of GBS early in the disease course have shown that the initial pathologic changes are localized to the node and are associated with deposition of activated complement and immunoglobulin G (IgG) and macrophage infiltration.12,13 Antiganglioside antibodies could bind target antigens in the nodal axolemma or paranodal myelin and trigger axonal destruction or demyelination. Physiologic conduction block induced by antiganglioside antibodies causing ionic channel blockade is a supl.ementary explanation for which the current evidence is intriguing but in conflict.10,14 What is the link between C. jejuni infection and antiganglioside antibodies? Several large studies have shown roughly a 50% concordance rate in GBS between serologic evidence of prior C. jejuni infection and the presence of anti-GM1 antibodies.5,15 Yuki et al.16 and others have found that the lipopolysaccharides of C. jejuni contain glycoconjugate epitopes similar to those in peripheral nerve, including GM1. A mechanism of molecular mimicry was proposed whereby the immune response to epitopes in C. jejuni would trigger antibody production, which would target the nodal gangliosides. Why does only about one person in 1000 with C. jejuni diarrhea get GBS?17 Only some strains of C. jejuni might carry a "neuropathic" factor. Alternatively, those who acquire GBS might have a host susceptibility factor. The sporadic rather than epidemic occurrence of GBS argues against a neuropathic strain. However, the occurrence of particular, otherwise rare, serotypes of C. jejuni in GBS cases in different populations-Penner type 19 in Japanese and Penner type 41 in South African GBS cases 5,18-remains to be explained. All nine isolates from the South African cases shared the same electrophoretic protein and DNA "fingerprint," which differed from that of the Penner type 41 biotype. So far, it has not been possible to identify a particular GBS-inducing factor in these or other isolates. Two articles in the current issue of Neurology address these issues. Sheikh et al.19 examined both axonal and demyelinating GBS cases from China and the United States. They examined whether there was a difference in the content of ganglioside-like moieties in C. jejuni isolated from patients with diarrhea and those who subsequently developed GBS and whether antiganglioside antibodies were produced equally in both groups. Similar to other investigators,5,20 they found no difference in the ganglioside-like moieties between the enteritis and neuropathic cases. However, the GBS cases all had significant elevations of antiganglioside antibodies, whereas the non-neuropathic cases did not. They concluded that this evidence was consistent with a host susceptibility factor but did not dismiss the possibility of an immunogenic factor in neuropathic C. jejuni strains not detected by current methods that could play a role in pathogenesis. Ma et al.21 sought evidence of host susceptibility by examining immune recognition factors, specifically T-cell receptors and human leukocyte antigen (HLA) molecules, in 81 Japanese GBS patients and controls. They found no significant difference in HLA markers between groups. They examined T-cell receptor alpha chain constant and beta chain variable gene polymorphisms and found no difference. However, three other studies have provided some evidence of HLA associations in GBS. Rees et al.22 found an increased frequency of HLA DQB1*03 in British GBS patients with preceding C. jejuni infection and Yuki et al.23 found that all six Japanese patients with C. jejuni-associated GBS had HLA B35. Monos et al.24 found an association between the demyelinating form of GBS and HLA DRB1*1301 in Chinese patients. An association with HLA and T-cell receptor genes would be expected if T-cell responses to C. jejuni peptides cross-react with myelin protein peptides and induce inflammatory neuropathy by a pathogenetic mechanism resembling that in EAN. The problem is that several infectious agents, such as cytomegalovirus and Mycoplasma pneumoniae, as well as several strains of C. jejuni, can trigger GBS. Furthermore, at least three different proteins can induce EAN, namely P0, P2, and PMP22, and probably several different peptides within each protein.6,7 Consequently, the initiating T-cell responses are likely to be as heterogeneous as the precipitating infections and the clinical features of GBS. Confirming associations with T-cell and HLA genes will require very large series from which large, homogeneous groups can be extracted and compared with appropriate controls. Much has been learned about GBS and its variants. The presence of antiganglioside antibodies is intriguing but their role remains uncertain. C. jejuni is one organism that can trigger an antiganglioside response and induce GBS in a susceptible host. The search for that host susceptibility factor remains a major task.

Imprenta: Neurology, v. 51, n. 2, p. 340-342, 1998

Identificador do objeto digital: 10.1212/WNL.51.2.340

Descritores: Guillain-Barre Syndrome - Pathogenesis ; Guillain-Barre Syndrome - Proteins ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Immunology

Data de publicação: 1998

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