THE HUD PARANEOPLASTIC PROTEIN SHARES IMMUNOGENIC REGIONS BETWEEN PEMPSN PATIENTS AND SEVERAL STRAINS AND SPECIES OF EXPERIMENTAL-ANIMALS/

Patients with small-cell carcinoma of the lung and paraneoplastic ence phalomyelitis develop antibodies (anti-Hu) against HuD, a member of a family of neuronal specific RNA-binding proteins, which are also expre ssed by the tumor. In order to determine if the human HuD paraneoplast ic antigen shares immunogenic regions between patients and several str ains and species of animals, we immunized animals with HuD and several deletion constructs of this protein. All immunized animals developed high titers of anti-HuD antibodies, comparable to the antibody titers found in paraneoplastic patients. Using immunohistochemistry and Weste rn blot analysis of human and mouse cerebral cortex, the pattern of re activity of these antibodies could not be differentiated from the huma n paraneoplastic anti-Hu antibodies. None of the immunized animals dev eloped neurologic symptoms. Western blot analysis of HuD deletion cons tructs demonstrated that the first and second RNA binding domains were the main immunodominant regions, and that the animal immune response was both strain and species dependent.