Hel‐N1 is a novel human complementary DNA encoding a neuronal RNA‐binding protein which shares considerable sequence homology with the HuD protein, a target of type I anti–neuronal nuclear antibodies in patients with paraneoplastic encephalomyelitis. The aim of the present study was to determine the prevalence of antibodies against the Hel‐N1 protein among patients with lung carcinoma, including those with paraneoplastic disorders. Sera from 45 patients with lung cancer (42 with small‐cell carcinoma) and from 28 control patients with other neurological diseases were studied by enzyme‐linked immunosorbent assay (ELISA) and by immunoblotting with recombinant Hel‐N1 protein. Sixteen of the 45 lung cancer patients (14 with small‐cell and 2 with undifferentiated carcinoma) had paraneoplastic encephalomyelitis and high‐titer type I anti–neuronal nuclear antibodies; sera from each of these 16 patients also showed strong reactivity with Hel‐N1 protein. The other 29 lung cancer patients, all of whom had neurological dysfunction and 24 of whom had known or suspected paraneoplastic disorders, lacked the type I antibody by standard testing. The mean anti–Hel‐N1 titer (by ELISA) of sera from patients negative for type I anti–neuronal nuclear antibody was significantly less than that of the patients positive for the type I antibody, but exceeded that of the control patients with other neurological diseases (p < 0.001). Fifteen (52%) of the 29 type I antibody–negative patients had positive serum anti–Hel‐N1 titers which did not overlap the high anti–Hel‐N1 titers of the 16 type I antibody–positive patients. These findings support the theory that type I anti–neuronal nuclear antibodies react with a family of neuronal RNA‐binding proteins, and suggest that these proteins share one or more epitopes. High titers of circulating anti–Hel‐N1 antibodies correlate with paraneoplastic encephalomyelitis, while lower anti–Hel‐N1 titers are present in a sizeable proportion of patients with small‐cell lung cancer without a clear association with their clinical condition.
ASJC Scopus subject areas
- Clinical Neurology