Campylobacter species and Guillain-Barré syndrome

Abstract

Since the eradication of polio in most parts of the world, Guillain-Barré syndrome (GBS) has become the most common cause of acute flaccid paralysis. GBS is an autoimmune disorder of the peripheral nervous system characterized by weakness, usually symmetrical, evolving over a period of several days or more. Since laboratories began to isolate Campylobacter species from stool specimens some 20 years ago, there have been many reports of GBS following Campylobacter infection. Only during the past few years has strong evidence supporting this association developed. Campylobacter infection is now known as the single most identifiable antecedent infection associated with the development of GBS. Campylobacter is thought to cause this autoimmune disease through a mechanism called molecular mimicry, whereby Campylobacter contains ganglioside-like epitopes in the lipopolysaccharide moiety that elicit autoantibodies reacting with peripheral nerve targets. Campylobacter is associated with several pathologic forms of GBS, including the demyelinating (acute inflammatory demyelinating polyneuropathy) and axonal (acute motor axonal neuropathy) forms. Different strains of Campylobacter as well as host factors likely play an important role in determining who develops GBS as well as the nerve targets for the host immune attack of peripheral nerves. The purpose of this review is to summarize our current knowledge about the clinical, epidemiological, pathogenetic, and laboratory aspects of campylobacter-associated GBS.

FIG. 1

Interrelationships among the forms of GBS. Reprinted from reference with permission of the publisher.

FIG. 2

Immunopathology of the AIDP form of GBS. (A) Nerve fiber stained with markers of complement activation C3d on the outermost surface of the Schwann cell; (B) electron micrograph showing early vesicular changes in the myelin sheath (m); (C) macrophages participate in the removal of damaged myelin; (D) cartoon of the overall process. Reprinted from reference with permission of the publisher.

FIG. 3

Immunopathology of the AMAN form of GBS. (A) Immunostained nerve fiber showing presence of C3d on the node of Ranvier (arrow); (B) macrophage recruitment to the nodes and insertion (arrowheads) into the nodal gap (arrow); (C) electron micrograph showing a macrophage surrounding the axon (A) in the periaxonal space without damage to the myelin (M); (D) cartoon depicting the entire process. Reprinted from reference with permission of the publisher.

FIG. 4

Structures of different gangliosides with terminal saccharide structures as reported for isolates of C. jejuni.

FIG. 5

Known structures of core molecules and O antigen-like polysaccharides from C. jejuni serotypes that contain potential cross-reactive epitopes with different gangliosides. O:1 contains a GM2-like epitope; O:2 contains a GM4 epitope; O:3 contains no cross-reactive epitope; O4 contains a GD1a epitope; O:10 contains a GT1a-like epitope; O:19 may contain several ganglioside epitopes, including GM1 and GD1a, but also GT1a and GD3 (not shown); and O:23/36 contains a GM2-like epitope. Also see the review by Moran et al. (108). Courtesy of Ben Fry.