Paraneoplastic Anti-Neuronal Nuclear IgG Autoantibodies (Type I) Localize Antigen in Small Cell Lung Carcinoma

Type I anti-neuronal nuclear autoantibodies (ANNA-I, also known as “Hu”) are a distinctive serologic marker of small cell lung carcinoma (SCLC) in patients who have peripheral neuropathies or encephalomyeloradiculopathies. A tumor antigen reactive with these antibodies has been identified by other investigators by Western blot analyses, but an antigen has not been localized in SCLC immunohistochemically. We therefore tested, by indirect immunofluorescence, the sera of 49 sequential ANNA-I-positive patients and 30 control subjects for IgG reactive with SCLC. Two tumor cell lines were tested, one established from the primary tumor of a patient with Lambert-Eaton syndrome and the second from the metastatic lesion of a patient without neurologic disease. IgG in all ANNA-I-positive sera bound to both tumors. In most instances, the pattern resembled that seen in neurons, with strong homogeneous nuclear staining, sparing of nucleoli, and faint cytoplasmic staining. A highly significant correlation was noted between endpoint dilutions obtained on SCLC substrates and on central and peripheral neurons (r = 0.863; P<0.001). IgG in 3 of 30 control sera bound in low titer to SCLC cells but not to neurons, and 9 control sera contained non-organ-specific anti-nuclear antibodies (ANA). The ANA IgG was absorbed equivalently by homogenates of SCLC or colonic adenocarcinoma cells. In contrast, the reactivity of ANNA-I IgG with cerebellar and myenteric plexus neurons was absorbed only by homogenized SCLC cells. These findings suggest that SCLC antigens account for all neuronal reactivity of ANNA-I. IgG of this specificity may serve as a useful reagent for identifying SCLC cells in surgical pathologic and cytologic specimens.