Exploration of Anti-Yo and Anti-Hu paraneoplastic neurological disorders by PhIP-Seq reveals a highly restricted pattern of antibody epitopes
Exploration of Anti-Yo and Anti-Hu paraneoplastic neurological disorders by PhIP-Seq reveals a highly restricted pattern of antibody epitopes
ABSTRACT Paraneoplastic neurological disorders (PNDs) are immune-mediated diseases of the nervous system understood to manifest as part of a misdirected anti-tumor immune response. Identifying PND-associated autoantibodies and their cognate antigens can assist with proper diagnosis and treatment while also enhancing our understanding of tumor-associated immune processes, triggers for autoimmune disease, and the functional significance of onconeuronal proteins. Here, we employed an enhanced version of phage display immunoprecipitation and sequencing (PhIP-Seq) leveraging a library of over 731,000 unique phage clones tiling across the entire human proteome to detect autoantibodies and create high-resolution epitope profiles in serum and CSF samples from patients suffering from two common PNDs, the anti-Yo (n = 36 patients) and anti-Hu syndromes (n = 44 patients). All patient samples positive for anti-Yo antibody by a validated clinical assay yielded polyspecific enrichment of phage presenting peptides from the canonical anti-Yo (CDR2 and CDR2L) antigens, while 38% of anti-Hu patients (17/44) had a serum and/or CSF sample that significantly enriched peptides deriving from the ELAVL family of proteins, the anti-Hu autoantigenic target. The anti-Hu antibodies showed a remarkably convergent antigenic signature across 15/17 patients corresponding to residues surrounding and including the degenerate motif, RLDxLL, shared by ELAVL2, 3 and 4. Lastly, PhIP-Seq identified several known and novel autoantigens in these same patient samples, representing potential biomarkers that could aid in the diagnosis and prognosis of PND and cancer.
Vazquez Sara E.、Anderson Mark S.、Zekeridou Anastasia、O?ˉDonovan Brian、Liu Jamin、Kassimatis Travis、Parent Audrey V.、Pittock Sean J、Mandel-Brehm Caleigh、Chow Eric、Hauser Stephen L.、DeRisi Joseph L.、Wilson Michael R.
Department of Biochemistry and Biophysics, University of CaliforniaDiabetes Center, University of CaliforniaDepartment of Neurology, Department of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Biochemistry and Biophysics, University of CaliforniaDepartment of Biochemistry and Biophysics, University of California||UC Berkeley-UCSF Graduate Program in Bioengineering, University of CaliforniaDepartment of Biochemistry and Biophysics, University of CaliforniaDiabetes Center, University of CaliforniaDepartment of Neurology, Department of Laboratory Medicine and Pathology, Mayo ClinicDepartment of Biochemistry and Biophysics, University of CaliforniaDepartment of Biochemistry and Biophysics, University of CaliforniaWeill Institute for Neurosciences, Department of Neurology, University of CaliforniaDepartment of Biochemistry and Biophysics, University of California||Chan Zuckerberg Biohub, University of CaliforniaWeill Institute for Neurosciences, Department of Neurology, University of California
神经病学、精神病学基础医学医学研究方法
Vazquez Sara E.,Anderson Mark S.,Zekeridou Anastasia,O?ˉDonovan Brian,Liu Jamin,Kassimatis Travis,Parent Audrey V.,Pittock Sean J,Mandel-Brehm Caleigh,Chow Eric,Hauser Stephen L.,DeRisi Joseph L.,Wilson Michael R..Exploration of Anti-Yo and Anti-Hu paraneoplastic neurological disorders by PhIP-Seq reveals a highly restricted pattern of antibody epitopes[EB/OL].(2025-03-28)[2025-04-29].https://www.biorxiv.org/content/10.1101/502187.点此复制
评论