Rxivist logo

Exploration of Anti-Yo and Anti-Hu paraneoplastic neurological disorders by PhIP-Seq reveals a highly restricted pattern of antibody epitopes

By Brian O’Donovan, Caleigh Mandel-Brehm, Sara E Vazquez, Jamin Liu, Audrey V. Parent, Mark S Anderson, Travis Kassimatis, Anastasia Zekeridou, Stephen L. Hauser, Sean J Pittock, Eric Chow, Michael R Wilson, Joseph L. DeRisi

Posted 20 Dec 2018
bioRxiv DOI: 10.1101/502187 (published DOI: 10.1093/braincomms/fcaa059)

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.

Download data

  • Downloaded 1,495 times
  • Download rankings, all-time:
    • Site-wide: 18,331
    • In immunology: 650
  • Year to date:
    • Site-wide: 53,961
  • Since beginning of last month:
    • Site-wide: 50,993

Altmetric data


Downloads over time

Distribution of downloads per paper, site-wide

PanLingua

News