HU ANTIGENS - REACTIVITY WITH HU ANTIBODIES, TUMOR EXPRESSION, AND MAJOR IMMUNOGENIC SITES

HuD, a human neuronal RNA-binding protein, was the first identified me mber of a family of antigens that also includes HuC and Hel-N1 (Hu ant igens). The serum of all patients with anti-Hu-associated paraneoplast ic encephalomyelitis and sensory neuronopathy react with HuD and Hel-N 1, but the reactivity with HuC is unknown. In the current study we exa mined (I) the reactivity of anti-Hu sera with HuD, HuC, and Hel-N1; (2 ) the expression of HuD, HuC, and Hel-N1 messenger RNA in small-cell l ung cancer of patients with and those without paraneoplastic encephalo myelitis/sensory neuronopathy; (3) the correlation between anti-Hu ser um reactivity with these three Hu antigens and the type of neurologica l symptoms; and (4) the major immunogenic sites of HuD. Our findings i ndicate that all anti-Hu sera react with HuD, HuC, and Hel-N1. However , only HuD is expressed in the small-cell lung cancer tumors, indicati ng that among the three Hu antigens, HuD appears to play a central rol e in triggering the anti-Hu immune response. No differences were ident ified regarding the reactivity of the anti-Hu antibodies with HuD, HuC , and Hel-N1 and the spectrum of neurological symptoms presented by th e patients. Study of the major immunogenic sites of HuD resulted in th e identification of two major immunodominant regions with at least two distinct epitopes recognized by the serum of all patients with anti-H u-associated paraneoplastic encephalomyelitis/sensory neuronopathy.