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Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

Lookup NU author(s): Professor Jordi Diaz ManeraORCiD

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

© 2018 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. Objective: Paraneoplastic neurological syndromes (PNS) are rare neurological disorders in which ectopic expression of neural antigens by a tumor results in an autoimmune attack against the nervous system. Onconeural antibodies not only guide PNS diagnosis but may also help detecting underlying malignancies. Our project aims to uncover new potential antibodies in paraneoplastic neuropathies (PN). Methods: Thirty-four patients fulfilling diagnostic criteria of possible (n = 9; 26.5%) and definite (n = 25; 73.5%) PN without onconeural antibodies and 28 healthy controls were included in our study. Sera were tested for known antibodies against neural cell adhesion molecules and screened for novel IgG and IgM reactivities against nerve components: dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells. Patients showing autoantibodies against any of these cell types were used for immunoprecipitation (IP) studies. Results: Overall, 9 (26.5%) patients showed significant reactivity against DRG neurons, motor neurons, or Schwann cells, whereas 5 (17.9%) healthy controls only showed moderate reactivity. Compared with control sera, serum samples from patients with paraneoplastic sensory-motor neuropathies had a higher frequency of IgM antibodies against Schwann cells (0% vs. 40%; P = 0.0028). No novel antigens were identified from our IP experiments. Antibodies against the neural adhesion molecules CNTN1, NF155, NF140, NF186, NCAM1, L1CAM, and the CNTN1/CASPR1 complex were not detected in patients with PN. One (2.9%) patient with CIDP and thymoma had CASPR2 antibodies. Interpretation: Almost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm-associated antigens remain to be discovered.


Publication metadata

Author(s): Siles AM, Martinez-Hernandez E, Araque J, Diaz-Manera J, Rojas-Garcia R, Gallardo E, Illa I, Graus F, Querol L

Publication type: Article

Publication status: Published

Journal: Annals of Clinical and Translational Neurology

Year: 2018

Volume: 5

Issue: 5

Pages: 559-569

Print publication date: 01/05/2018

Online publication date: 26/03/2018

Acceptance date: 22/02/2018

Date deposited: 27/02/2020

ISSN (electronic): 2328-9503

Publisher: Wiley-Blackwell

URL: https://doi.org/10.1002/acn3.554

DOI: 10.1002/acn3.554


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Funding

Funder referenceFunder name
FIS16/00627

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