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Ann Clin Transl Neurol. 2018 Mar 26;5(5):559-569. doi: 10.1002/acn3.554. eCollection 2018 May.

Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies.

Author information

1
Neuromuscular Diseases Unit Neurology Department Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.
2
Centro para la Investigación Biomédica en Red en Enfermedades Raras (CIBERER) Madrid Spain.
3
Service of Neurology and Neuroimmunology August Pi Sunyer Biomedical Research Institute (IDIBAPS) Hospital Clínic University of Barcelona Spain.

Abstract

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.

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