Analyses Of Neural Autoantibodies By a Clinical Laboratory For The Evaluation Of Paraneoplastic And Non-Paraneoplastic Neuronal Disorders (P6.001)

OBJECTIVE: To determine the frequency of a subset of neural autoantibodies (NA) associated with non-specific paraneoplastic disorders (NPD), cerebellar degeneration (CD), and autoimmune encephalitis (AE). BACKGROUND: Early identification of NA may improve patient prognosis by prompting the early treatment of an underlying malignancy. The nonspecific and overlapping nature of neurological symptoms necessitates an analysis of several autoantibodies to improve diagnostic accuracy. DESIGN/METHODS: We calculated the frequency of 16 autoantibodies from panels ordered for NPD, CD, and AE using de-identified test results (n=4,024) reported by a CLIA-certified clinical laboratory between 2011 and 2012. RESULTS: The AE panel (n=704) had the highest positive rate (6.3%), the majority being NR1 (29.5%) and LGI1/VGKC (18.2%). Hu, GAD65, LGI1, VGKC, and CASPR2 were equal at 9.1%. CV2, MaTa, and Amphiphysin were less common (6.8%). The CD panel (n=978) had the lowest frequency of autoantibodies (3.2%) composed of GAD65 (41.9%), Yo (25.8%) Hu (9.7%), Ri (9.7%), Amphiphysin (6.5%), Zic4/GAD65 (3.2%) and CV2 (3.2%). The 16 autoantibody NPD panel had a 4.6% positive rate. Most were explained by nAChR (23.1%), LG1/VGKC alone or in combination (19.5%), GAD65 (13.9%), NR1 (10.2%), Hu (6.5%), and CASPR2 (6.5%). The other autoantibodies were less than 4% each. Autoantibodies were found in 4.9% of all panels with GAD65 being the most frequent single marker (16.3%), followed by nAChR (12.8%), NR1 (12.2%), VGKC (9.7%), LGI1 (9.2%), Hu (7.1%), Yo (6.1%), and CASPR2 (5.6%). Other autoantibodies (Ri, CV2, Amphiphysin, MaTa, recoverin, VGCC, Zic4) and their combinations constituted the remaining 21%. CONCLUSIONS: Autoantibodies associated with NPD, AE, or CD were twice as likely to react with GAD65 or antigens of the neuron cell surface (nAChR, NR1, VGKC, and LGI1) as compared to classical onconeural antigens (Hu, Yo, Ri, Amphiphysin, MaTa, recoverin). These findings underscore the importance of multiparametric antibody diagnostics. Study Supported by: Quest Diagnostics Disclosure: Dr. Brachet has received personal compensation for activities with Quest Diagnostics. Dr. Jaremko has received personal compensation for activities with Quest Diagnostics. Dr. Sansoucy has received personal compensation for activities with Quest Diagnostics. Dr. Batish has received personal compensation for activities with Quest Diagnostics. Dr. Batish holds stock and/or stock options in Quest Diagnostics, which sponsored research in which Dr. Batish was involved as an investigator. Dr. Batish has received research support from Quest DIagnostics. Dr. Morneau has received personal compensation for activities with Quest Diagnostics. Dr. Wang has received personal compensation for activities with Quest Diagnostics. Dr. Levy has received personal compensation for activities with ApoPharma Inc. as a speaker. Dr. Levy has received research support from ApoPharma Inc. Dr. Burnham has received personal compensation for activities with Quest Diagnostics. Dr. Higgins has received personal compensation for activities with Quest Diagnostics. Dr. Higgins has received license fee payments from Jackson Laboratories. Dr. Higgins has received research support from Quest Diagnostics.