Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies

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 CNTN 1, NF 155, NF 140, NF 186, NCAM 1, L1 CAM , and the CNTN 1/ CASPR 1 complex were not detected in patients with PN . One (2.9%) patient with CIDP and thymoma had CASPR 2 antibodies. Interpretation Almost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm‐associated antigens remain to be discovered.