Myelin Basic Protein as an Encephalitogen in Encephalomyelitis and Polyneuritis Following Rabies Vaccination

Encephalitis and polyneuritis occurring after rabies vaccination are believed to be immunologically mediated. We studied antibody responses to neural antigens in 36 patients with major neurologic complications, 25 with minor complications, and 39 with no complications after immunization with a brain-derived, Semple rabies vaccine. Patients with major complications had significantly elevated levels of antibody to brain white matter as compared with the other groups (P<0.001). Assays for antibody to selected central nervous system antigens showed that high levels of serum and cerebrospinal fluid antibody to myelin basic protein correlated with the presence of major neurologic complications (both central and peripheral nervous systems). The level of antibody to cerebroside correlated best with the number of injections of vaccine, but like antibody to myelin basic protein, the antibody to cerebroside was present in the cerebrospinal fluid of patients with major complications. Some patients with major complications also had antibodies directed to the gangliosides GD^1b and GT^1b. No antibodies to myelin-associated glycoprotein were detected in any of the samples. These data implicate myelin basic protein as an encephalitogen in these autoimmune diseases of the human nervous system, but suggest that immune responses to cerebroside and certain gangliosides may have an augmentative role in severe disease. (N Engl J Med 1987; 316:369–74.), EARLY observations of neuroparalytic accidents due to rabies vaccines provided a foundation for current concepts of immunopathological mechanisms in demyelinating diseases. The encephalomyelitis and polyneuritis complicating the use of vaccines prepared in neural tissues are inflammatory, demyelinating diseases. Early studies indicated that these diseases were not caused by attenuated or inactivated rabies virus, but by “some component of the nerve substance” in the vaccine.¹ This conclusion led Rivers and Schwentker to inoculate monkeys repeatedly with homogenates of normal rabbit brain, which resulted in the first induction of experimental allergic encephalomyelitis.² Once Kabat and his associates³ induced the disease with a…