Background and Aims

Onconeural antibodies are well-known markers of paraneoplastic neurological syndromes (PNS). Antibody screening plays an important role in prompt tumour diagnosis because in up to 75% of patients the neurological symptoms precede the tumour diagnosis. Antibody detection based on brain tissue followed by antigen specific techniques, such as immunoblot, have demonstrated high sensibility and specificity for PNS. For practical reasons many clinical diagnostic laboratories use only immunoblot for onconeural antibody testing.

To assess the PNS-specificity of immunoblot for onconeural antibody testing.

Methods

We reviewed all the patients tested for onconeural antibodies from October 1, 2016 until August 31, 2019 by an in-house immunohistochemistry on paraformaldehyde perfused rat cerebellum and by a commercial line blot assay (PNS12 Euroline Blot, Euroimmun). Reasons for additional testing by blot were confirmation of a suspicious positive result by immunohistochemistry or specific request to test the sample by line blot.

Results

96 patients’ sera showed positive bands for onconeural antibodies using immunoblot. Immunoblot bands matched with the brain immunohystochemical findings in 45 patients (46.9%) whereas the other 51 (53.1%) showed discordant results. Clinical information was available in 45 and 46 patients respectively. 40 (88.9%) of the 45 patients with concordant immunoblot and immunohistochemistry results had PNS, whereas only 4 (8.7%) of the 46 patients with discordant results had PNS. Discordant results were more common with Yo (70%) and Zic4 (74%) antibodies.

Conclusions

Onconeural antibody testing by immunoblot is highly sensitive but shows low specificity for the diagnosis of PNS. This low specificity is more prominent for Yo and ZIC4 antibodies.