Year-end Sale % OFF 
Abstract
The goal of this study is to determine whether patients with paraneoplastic cerebellar degeneration (PCD) and small-cell lung cancer (SCLC) have a specific repertoire of antibodies, if SOX1 antibodies (SOX1-ab) can predict the presence of SCLC, and if antibodies to cell surface antigens occur in this syndrome. Antibody analysis was done using immunohistochemistry on rat brain, immunoblot with recombinant antigens, screening of cDNA expression libraries, and immunolabeling of live neurons in 39 patients with PCD and SCLC. VGCC-ab were measured by RIA, and SOX1-ab, Hu-ab, and ZIC4-ab by immunoblot. Lambert-Eaton myastenic syndrome (LEMS) was present in 10 of 23 patients with electrophysiological studies. At least one antibody was detected in 72% of patients. The individual frequencies were: 49% SOX1-ab, 44% VGCC-ab, 31% Hu-ab, and 13% ZIC4-ab. SOX1-ab occurred in 76% of patients with VGCC-ab and 27% of those without VGCC-ab (p = 0.0036). SOX1-ab were not found in 39 patients with sporadic late-onset cerebellar ataxia, 23 with cerebellar ataxia and glutamic acid decarboxylase antibodies, and 73 with PCD and cancer types other than SCLC (31 without onconeural antibodies, 25 with Yo-ab , 17 with Tr-ab). Five patients (13%) had antibodies against unknown neuronal cell surface antigens but none of them improved with immunotherapy. One serum immunoreacted against the axon initial segment of neurons and another serum against ELKS1, a protein highly expressed in the cerebellum that interacts with the beta4-subunit of the VGCC. In conclusion, 72% of patients with PCD and SCLC had one or more antibodies that indicate the presence of this tumor. In these patients, VGCC-ab and SOX1-ab occur tightly associated. SOX1-ab are predictors of SCLC in ataxia patients with a specificity of 100% and sensitivity of 49%. Unlike limbic encephalitis with SCLC, antibodies to cell surface antigens other than VGCC-ab, are infrequent and do not predict response to treatment.
Highlights
The Purkinje cell is one of the most common targets of the immune response that some patients with cancer built up against antigens shared by the tumor and the nervous system [1]
In the current study we wanted to determine if patients with paraneoplastic cerebellar degeneration (PCD) and Small-cell lung cancer (SCLC) had antibodies other than voltage-gated calcium channels (VGCC)-ab that could explain the cerebellar ataxia or at least to help in the diagnosis of PCD
The isolated determination of VGCC-ab in a patient with cerebellar ataxia with or without LambertEaton myasthenic syndrome (LEMS) almost always confirms a paraneoplastic origin because the clinical association of cerebellar ataxia and LEMS very rarely occur in absence of cancer [12,13]
Summary
The Purkinje cell is one of the most common targets of the immune response that some patients with cancer built up against antigens shared by the tumor and the nervous system [1]. The death of Purkinje cells results in a pancerebellar syndrome called paraneoplastic cerebellar degeneration (PCD) [1]. Small-cell lung cancer (SCLC) is one of the most common tumors that associate with PCD [2]. Whereas many patients (.80%) with other paraneoplastic neurological syndromes and SCLC harbor Hu antibodies (Hu-ab), the frequency of Hu-ab in PCD is low (23%) [3]. 40% of PCD patients with SCLC have antibodies to voltage-gated calcium channels (VGCC), and some present clinical or neurophysiological evidence of LambertEaton myasthenic syndrome (LEMS) [3]. Up to 60% of patients with LEMS and SCLC have SOX1-ab, a serologic marker of SCLC [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
