Paraneoplasia and Autoimmunologic Injury of the Nervous System: The Anti‐Hu Syndrome

Abstract

In recent years, antineuronal autoantibodies of varying antigenic specificity have come to be associated with a number of paraneoplastic neurologic disorders. Anti-Hu is a polyclonal complement-fixing IgG directed against a 35 to 40 kilodalton protein concentrated in the nuclei of neurons throughout the central and peripheral neuraxes. Its elaboration at high titer in serum and cerebrospinal fluid is invariably associated with a neurologic syndrome characterized chiefly by subacutely evolving sensory neuropathy and an array of central disturbances that include bulbar and cerebellar dysfunction, limbic encephalitis and motor neuron disease. The manufacture of anti-Hu IgG is triggered in a great majority of cases by underlying small cell carcinomas of pulmonary origin, typically limited in stage and otherwise silent, that aberrantly express the native neuronal antigen or an antigenically indistinguishable epitope. Both neoplastic and diseased neural tissues contain lymphocytes of B and T lineage specifically cognizant of the Hu antigen as well as concentrated anti-Hu IgG bound to tumor cells and neurons, respectively. These observations suggest that an immune response serving initially to limit the growth and spread of its inciting neoplasm comes subsequently to be misdirected against the nervous system of the host, resulting in autoimmunologically-mediated neurologic injury. Clinical, neuropathologic and immunologic data derived from a series of 71 sero-confirmed cases of the anti-Hu-associated paraneoplastic sensory neuronopathy/encephalomyelitis complex are reviewed.