Building Paraneoplastic and Disease-Specific Autoimmune Neurology Testing for a National Reference Laboratory
Ajay Grover1, Stanley Naides1, Andre Valcour1, Vincent Ricchiuti1, Mindy Nye1, Joseph Volpe1
1LabCorp
Objective:

Develop and validate paraneoplastic syndrome and other autoimmune neurological tests and panels based on Paraneoplastic Syndrome (PNS)-Care panel recommendations and phenotype-based focus.

Background:

Autoantibody testing for neurological diseases such as paraneoplastic disorders, encephalopathies, and myelopathies has become increasingly complex over time due to the discovery of new biomarkers. The growing number of options for antibody panel testing can create confusion amongst ordering clinicians and lead to either ordering concurrently several overlapping panels or repeat panel evaluations. There is an urgent need for the development and standardization of neurological autoimmune and paraneoplastic autoantibody testing based on new practice standards and phenotype-based selection.

Design/Methods:

We designed and validated a comprehensive paraneoplastic profile that included a combination of high-, intermediate- and low-probability antibodies associated with cancer. A “catch-all algorithm” consisting of 25 antibody markers was designed for the situation when a clear clinical presentation is absent, but a neurological condition associated with a neoplasm is suspected. A phenotype-based algorithm was designed by choosing neurological condition-specific markers and the appropriate methods for optimal sensitivity and specificity. A combination of assay methods such as immunofluorescence on multiple neural and non-neural tissue substrates, immunofluorescence on HEK293 target transfected substrate, enzyme immunoassay, radioimmunoassay, and line blot assay was used to design testing profiles suitable for different autoimmune neurological conditions.

Results:
A comprehensive autoimmune neurology/paraneoplastic profile was developed and validated for testing of the patients in a large national reference laboratory. Other phenotype-specific profiles were also validated for autoimmune conditions such as encephalopathy, epilepsy, rapid onset dementia, axonal neuropathy, and myelopathy. A follow-up study using these validated tests in our laboratory showed that for the patients who had any reactive autoantibody, the distribution was approximately 25% positive for GAD65, 20% VGKC (LGI1/CASPR2), 15% to NMDAR1, 10% to VGCC and the remaining 30% were reactive for assorted other targets.  
Conclusions:
NA
10.1212/WNL.0000000000202769