24 - Neuronal nuclear autoantibodies, type 1 (Hu)

Abstract

Antineuronal nuclear autoantibody type 1 (Hu) was initially described in two patients with sensory neuronopathy and small cell lung carcinoma (SCLC). Hu antibodies (Huab) recognize several members of the Hu family whose expression is tightly restricted to neurons and SCLC cells. Hu antigens are important for the development and maintenance of the neuronal phenotype, probably through the control of the expression of multiple neuronal genes. Hu-ab are screened by immunohistochemistry on brain sections, and confirmed by immunoblot of purified antigen (HuD). Low titers of Hu-ab are present in 16% of patients with SCLC and no neurological disease. High titers are restricted to patients with paraneoplastic neurological syndromes (PNS), almost always associated with SCLC and, in less than 20% of the cases, other tumor types. The most common PNS associated with Hu-ab are sensory neuronopathy, gastrointestinal motor dysfunction, paraneoplastic cerebellar degeneration, brainstem, and limbic encephalitis, or the combination of the above syndromes (paraneoplastic encephalomyelitis). Hu-ab (with high titers) has a high specificity for PNS (99%) and a sensitivity that ranges from 82% in sensory neuronopathy to 23% in cases of cerebellar degeneration and SCLC. Hu-ab are not found in normal subjects or patients with neurological diseases other than PNS. Up to 4% of patients with clinical syndromes identical to the PNS described above and Hu-ab never develops cancer. Hu-ab does not have prognostic value for either the PNS or tumor outcome, and they should not be used to monitor disease evolution. Hu-ab does not play a role in the pathogenesis of the PNS. The current thinking is that Hu-ab is markers of a more complex immune response against Hu antigens and that the PNS is caused by Hu-specific cytotoxic T cells.