Autoantibodies against the Hel-N1 RNA-binding protein among patients with lung carcinoma: An association with type I anti-neuronal nuclear antibodies

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Abstract
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.