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Published on: June 29, 2016
Antibodies against cell adhesion molecules and neural structures in paraneoplastic neuropathies
Ana M Siles1,2, Eugenia Martínez-Hernández2,3, Josefa Araque1,2
1Neuromuscular Diseases Unit Neurology Department Hospital de la Santa Creu i Sant Pau Universitat Autònoma de Barcelona Barcelona Spain.
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.
Insights
Nearly 30% of paraneoplastic neuropathy patients have antibodies targeting neural structures. This suggests new tumor-associated antigens await discovery in these rare autoimmune disorders.
Area of Science:
- Neurology
- Immunology
- Oncology
Background:
- Paraneoplastic neurological syndromes (PNS) are rare autoimmune disorders triggered by cancer.
- Onconeural antibodies aid in diagnosing PNS and detecting underlying malignancies.
- Identifying novel antibodies is crucial for understanding and diagnosing paraneoplastic neuropathies (PN).
Purpose of the Study:
- To uncover new potential antibodies in patients with paraneoplastic neuropathies (PN).
- To investigate novel IgG and IgM reactivities against nerve components in PN patients.
Main Methods:
- Sera from 34 PN patients and 28 healthy controls were tested.
- Screening included novel reactivities against dorsal root ganglia (DRG) neurons, motor neurons, and Schwann cells.
- Immunoprecipitation (IP) studies were performed on patients with autoantibodies.
Main Results:
- Nine (26.5%) PN patients showed significant reactivity against neural structures.
- A higher frequency of IgM antibodies against Schwann cells was observed in PN patients compared to controls (40% vs. 0%).
- No novel antigens were identified via IP; known neural adhesion molecule antibodies were not detected.
Conclusions:
- Approximately 30% of PN patients possess antibodies targeting neural structures.
- The findings indicate that novel neoplasm-associated antigens remain to be discovered.
- Further research is needed to identify these novel antigens and improve diagnostic strategies for PN.
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