The localization, mode of action, and roles of complement in the Guillain-Barre syndrome have been controversial. We used high-resolution immunocytochemistry to localize complement activation products in early stages of the acute inflammatory demyelinating polyneuropathy (AIDP) pattern of Guillain-Barre syndrome. Three AIDP subjects who were autopsied had had symptoms for 3 to 9 days at the time of death. Immunocytochemistry was performed on etched, epoxy resin-embedded sections, and the next thin section was compared by electron microscopy (thick/thin sections). Many fibers had a rim of the complement activation marker C3d and the terminal complement complex neoantigen C5b-9 along the outer surface of the Schwann cells. Ultrastructural analysis of these C3d-positive fibers showed mild vesicular changes of the outermost myelin lamellae. Vesicular degeneration was seen before the invasion of macrophages into the myelin, and was the predominant change in the subject with symptoms for 3 days. C3d staining was not found on myelin membranes. The results suggest that at least some forms of AIDP are complement mediated. We speculate that complement is activated by antibody bound to epitopes on the outer surface of the Schwann cell and that the resulting complement activation initiates the vesiculation of myelin.

Immune attack on the Schwann cell surface in acute inflammatory demyelinating polyneuropathy.

In the second part of our review the role of antecedent infections in the pathogenesis of GBS is discussed. The association with Campylobacter jejuni (C. jejuni) is highlighted and the concept of molecular mimicry, i.e., sharing of epitopes between microbes and peripheral nerve, explained. Alternative mechanisms to relate an infection with the immune-mediated neuropathy are elaborated. Current therapies of the GBS include plasma exchange, high-dose intravenous immunoglobulins, and supportive treatment directed to secondary complications. Published therapeutic trials are reviewed and future approaches are outlined. Principles of general care are also summarized.© 1995 John Wiley &Sons, Inc.

Immunopathogenesis and treatment of the Guillain-Barré syndrome--Part I.

The Guillain-Barre syndrome is a distinctive neuropathy characterized pathologically by the presence of inflammatory lesions which occur scattered throughout the peripheral nervous system. The lesions consist of circumscribed areas in which myelin is lost in the presence of lymphocytes and macrophages. Myelin damage of effected largely by macrophages, which penetrate the basement membrane around nerve fibers and strip what appears to be normal myelin away from the body of the Schwann cell and off the axon. While there is evidence that this activity is immune mediated, the precise mechanism that leads macrophages to seek out and amputate a specialized region of the Schwann cell plasma membrane remains unexplained.

Pathology of the Guillain-Barré syndrome.

Evidence that Guillain-Barre syndrome (GBS) may be caused, at least in part, by antibodies to nerve tissue or soluble immune complexes is reviewed. Although insufficient proof exists at present to confirm a causal relationship between humoral factors and GBS, converging lines of evidence support this possibility.

The role of autoantibody and immune complexes in the pathogenesis of Guillain‐Barre syndrome

The in vivo demyelinating capacity of sera from 27 patients with Guillain-Barre syndrome (GBS) and 47 other individuals was studied by intraneural injection into rat sciatic nerves. The morphological features of the nerves in cross section taken just proximal to the site of needle insertion was assessed 48 hours after injection and the extent of demyelination was quantitated. All 27 GBS serum samples were obtained in the first three weeks of clinical disease. Of these, 11 (41%) produced demyelination. Demyelinative activity of GBS sera correlated only with severity of clinical disease (p less than 0.01). The extent of demyelination after intraneural injection of human sera was less intense on average than that produced by sera from animals with experimental allergic neuritis. Three of 40 (7.5%) sera obtained from normal subjects and patients with other neurological diseases also caused in vivo demyelination, although the activity was weaker and occurred less often than with GBS serum.

F. Gorce

Papers

The action of Guillain-Barré syndrome serum on myelin ☆: A tissue culture and electron microscopic analysis