Abstract
Detection of onconeural antibodies is important because establishes a definitive diagnosis of paraneoplastic neurological syndrome (PNS). The recommended method for diagnosis of onconeural antibodies is by immunohistochemistry on rodent brain sections and confirmation of results by immunoblot. However, in many diagnostic laboratories samples are only tested with commercial line blots. In this study we inquired whether this change in diagnostic methodology (line blot alone vs. combined immunohistochemistry and line blot) would affect the results. Among 439 samples examined by immunohistochemistry and a commercial line blot (Euroimmun, Lübeck, Germany) 96 (22%) were positive by line blot, and their clinical information was reviewed. Onconeural antibodies were detected by both assays in 46/96 (48%) patients (concordant group) whereas 50 (52%) were only positive by line blot (discordant group). In the concordant group 42/46 (91%) patients had a definite diagnosis of PNS whereas in the discordant group only 4/50 (8%) had PNS (p < 0.00001). None of the 14 patients with ZIC4 antibodies and 1/13 (8%) with Yo antibodies demonstrated only by line blot had PNS. These findings show a robust diagnostic value of combined diagnostic techniques, and both should be used to demonstrate onconeural antibodies, If antibody testing is performed only with line blot assay, positive bands should be confirmed by rodent brain immunohistochemistry. For ZIC4 or Yo antibody testing, line blot positivity with negative immunohistochemistry has no diagnostic significance, and for the rest of onconeural antibodies the predictive diagnostic value is low.
Highlights
Paraneoplastic neurological syndromes (PNS) include a group of neurological disorders in which an immune response against an underlying systemic tumor is misdirected to the nervous system causing the clinical manifestations (1)
Our study shows that the type of approach to onconeural antibody testing using line blot, immunohistochemistry, or both techniques strongly influences the accuracy in diagnosing PNS
91% of patients with onconeural antibodies demonstrated by line blot and rat immunohistochemistry had PNS compared to 8% of those with antibodies detected only by line blot
Summary
Paraneoplastic neurological syndromes (PNS) include a group of neurological disorders in which an immune response against an underlying systemic tumor is misdirected to the nervous system causing the clinical manifestations (1). Most PNS associate with onconeural antibodies against intracellular antigens (2) Since their initial description it was acknowledged that onconeural antibodies could occur in 5–15% of patients without cancer or in cancer patients without PNS (2). Initial studies on onconeural antibodies showed high specificity for distinct syndromes and tumors. These studies recommended onconeural antibody testing with rat brain immunohistochemistry and confirmation of results by immunoblot (2). We postulated that this limited testing approach greatly contributes to false positive results For this we assessed the frequency of PNS in patients with onconeural antibodies only demonstrated by line blot and compared it with the frequency of PNS in patients in whom the onconeural antibodies were confirmed by two diagnostic tests, line blot, and brain immunohistochemistry
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