Abstract 1277: Antigen-specific markers for paraneoplastic neurological syndromes obtained by proteomic analysis of patient immunoglobulins

Abstract

Abstract In the antibody response, as occurs in antitumor immunity, germline sequences are rearranged and mutated to generate a sequence with specificity for an antigen. In earlier work, it was shown that the antigen specificity of immune sera from rats can be distinguished by the proteomic analysis of immunoglobulins. It is hypothesized that the sequence of the antigen binding sites converges to a similar subset in individuals exposed to a given antigen. We therefore tested the applicability of our approach in patients with Paraneoplastic Neurological Syndrome (PNS). In these patients, a tumor triggers a well-characterized auto-immune response against onconeural antigens expressed in tumor and the affected part of the nervous system. These antibodies serve as markers for both the underlying tumor and specific neurological syndromes. Sera of 60 patients with PNS associated with paraneoplastic antibodies were analysed: 20 anti-HuD (18 lung cancer), 20 anti-Yo (6 breast, 9 gynecological and one other cancer), 10 anti-amphiphysin (4 lung, one breast and one other cancer), and anti-CV2 (6 lung cancer) antibodies. Antigen-specific immunoglobulins were collected by affinity enrichment on beads coated with recombinant antigen. The antigen-specific immunoglobulins were digested with trypsin and analyzed by nano-LC and mass spectrometry. From the resulting dataset, peptides were selected that uniquely identified one of the patient groups, and the peptide sequence was deduced from fragmentation spectra. 28 specific and unique peptides were found; 0 specific for amphiphysin, 2 specific for CV2, 11 for HuD and 15 for Yo. Several marker peptide sequences showed homology to known immunoglobulin sequences, and no relations were found to other known proteins from the NCBInr protein database. The data show that immunoglobulin-derived biomarkers can indeed be found in samples from patients and can serve as early markers of cancer and auto-immunity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1277. doi:1538-7445.AM2012-1277