Although the transmission of EAN by T cells sensitized to myelin is strong evidence of their role in GBS, antimyelin antibodies are probably involved in the initial part in the disease. The serum from patients with GBS damages myelin in tissue cultures and induces a characteristic (“vesicular”) form of myelin destruction. Subepineural injection of serum from GBS patients into the sciatic nerve of rats leads to local demyelination and electrical conduction block. The studies by Koski and associates of complement-dependent myelin damage by immunoglobulin (Ig) M antimyelin antibodies in GBS provided evidence that antimyelin antibodies are able to initiate myelin destruction even through T cells and that macrophages are the ultimate effectors of the damage. Indeed, the very earliest change that could be detected by Hafer-Macko and colleagues was the deposition of complement on the inner layer of myelin.
As mentioned earlier, circulating autoantibodies directed at components of nerve ganglioside are detected but only inconsistently in patients with GBS, the most predictable one being anti-GQ1b, which is found in almost all patients with ophthalmoplegia. Approximately one-fifth of patients have anti-GM1 antibodies early in their course, corresponding in most instances to a predominantly motor presentation and to axonal damage, the highest titers being associated with cases that follow Campylobacter infections. Antibodies directed against GD1a or GT1b are associated in some cases with the pharyngeal-brachial-cervical variant. Thus it would seem that casting GBS exclusively as a humoral or as a cellular immune process is an oversimplification. These antibody reactions have been summarized in a review by Yuki and Hartung.
An unanswered question is what incites the immune reaction isolated to peripheral nerves in humans. All attempts to identify a virus or microbial agent within nerves have failed and it is likely that a variety of agents—viral, bacterial (particularly C. jejuni), certain vaccines, and perhaps neural injury itself—are each capable, in susceptible individuals, of precipitating an immune response against components of autologous peripheral nerve. In outbreaks of Zika virus infection, there is a rise in cases of GBS as in the French Polynesian series reported by Cao-Lormeau and coworkers. The occurrence of GBS in patients with AIDS or with EBV or CMV infections simply indicates that these agents induce an autoimmune response without implicating a direct viral infection of nerve. However, the high frequency of the association with viruses such as these, and particularly Zika, suggests special antigen characteristics of organisms that cross-react with neural antigens.
The observation that only one of many individuals who are infected with a particular pathogen go on to develop GBS suggests that host factors are significant (there is, however, little consistency of human leukocyte antigen [HLA] types in GBS patients). Whether the aforementioned antibodies against various gangliosides of peripheral nerve are pathogenically active is also uncertain.
Several animal diseases—namely coonhound paralysis of dogs, Marek disease of chickens (a viral neuritis), and cauda equina neuritis of horses—resemble GBS superficially but do not share its main clinical or pathologic features.