Neuronal Nuclear Autoantibodies, Type 1 (Hu)

Antineuronal nuclear autoantibody type 1 (Hu) was initially described in two patients with sensory neuronopathy (SN) and small cell lung carcinoma (SCLC). Hu antibodies (Hu-ab) recognize nuclear antigens called Hu, which are members of a family of human neuronal ribonucleic acid (RNA)-binding proteins probably necessary for development and maintenance of the neuronal phenotype through the control of the expression of multiple neuronal genes. Hu antigens are 35-40-kDa proteins mostly expressed by the nuclei of neurons of the central nervous system (CNS) and peripheral nervous system and by SCLC cells. Hu-ab is a polyclonal, complement-fixing immunoglobulin (Ig)G. It is present in the serum and cerebrospinal fluid of patients with particular types of paraneoplastic neurologic syndromes (PNS) and SCLC. It is detected by immunohistochemistry on brain sections and confirmed by immunoblot of purified antigen (HuD). Normal subjects are seronegative. Hu-ab can be detected at low titer in the sera of about 15% of patients with SCLC in absence of a specific neurologic syndrome. High titers are restricted to patients with PNS, almost always associated with SCLC and less with other tumor types. Hu-ab have a specificity of 99% and a sensitivity of 82% in detecting PNS (sensitivity changes for different PNS).