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

ABSTRACT: 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).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.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.Almost 30% of patients with PN harbor antibodies targeting neural structures, suggesting that novel neoplasm-associated antigens remain to be discovered.

SUBMITTER: Siles AM

PROVIDER: S-EPMC5945957 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background and objectiveParaneoplastic neurological syndromes (PNS) are a group of rare syndromes associated with immunopathological process and tumors. Paraneoplastic autoantibodies are important for the diagnosis of PNS and for searching for underlying tumors. With the development of detection methods and discovery of new autoantibodies, the 2004 guidelines on PNS have recently been updated by a worldwide PNS-Care expert group. For clinicians, proper testing methods and testing results explanation are important for the diagnosis and treatment of PNS. This review aims to review the detection of paraneoplastic autoantibodies and the significance of testing results.MethodsWe summarize the studies on detection methods, association of autoantibodies and PNS or tumors, particularly the guidelines of PNS.Key content and findingsAntibodies are divided into 3 groups in the context of PNS according to the frequency of cancer association regardless of their eventual pathogenic effect. Instead of well-characterized antibodies and partially-characterized antibodies, high-risk antibodies, intermediate risk antibodies and lower risk antibodies were applied. According to the location of recognized antigens, these autoantibodies are divided as anti-intracellular antigen antibodies and neuronal surface antibodies (NSAbs). Tissue-based assays is recommended as screening method for paraneoplastic antibodies. Moreover, this method is helpful to discover new autoantibodies. A combination of a screening method [tissue-based assays (TBA)] and a confirmatory test [immunoblot and cell-based assay (CBA)] can improve sensitivity and specificity of the tests. Many PNSs are associated with specific antineuronal antibodies, but there is considerable diversity. Some autoantibodies are markers of specific neurological syndromes. Paraneoplastic antibodies are often specific for the PNS-associated tumor rather than for a particular neurological syndrome.ConclusionsDiagnosis of PNS depends on integrated analysis of clinical manifestations and auxiliary examinations. During diagnosis, selection of candidate antibodies for testing is challenging due to the varying clinical phenotypes and tumors associated with a given antibody. Broad antibody panels are more likely to capture causative antibodies and should be considered. According to different subtypes of autoantibodies, specific tumors or PNS should be considered. However, antibody titers, including cerebrospinal fluid (CSF) titers, should not be the primary driver of treatment decisions.

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

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