Autoimmune Encephalitis Panel, Serum (Sendout)

Test Information:

The Mayo Autoimmune Encephalitis Panel (serum) includes tests for 27 autoantibodies (as of 10/13/26), listed in the Mayo Autoimmune Neurology Antibody Matrix. This panel includes all 9 antibodies previously included in the serum paraneoplastic autoantibody panel (RPNPV, PAVAL). Oncologic associations for the autoantibodies in this panel are displayed in a table in the Antibody Matrix document.

Encephalitis is a debilitating neurologic condition caused by infectious and autoimmune conditions that result in inflammation of the brain parenchyma. The identification of autoantibodies may augment a diagnosis of autoimmune encephalitis, but is not required for the diagnosis or initiation of therapy. The most frequently identified antibodies target NMDA-R. NMDA Receptor IgG Antibody with Reflex, Serum (Sendout) [RNMDA] is recommended as first-line testing for autoimmune encephalitis prior to ordering this full panel, as outlined in the Autoimmune Encephalitis Testing Recommendations.

Monitoring titers over time for these antibodies is not recommended; however, this recommendation is based on limited currently available literature.

Test Algorithm: Refer to Mayo's algorithm (linked below) for additional detail on tests and potential reflex tests included in this panel. Reflex testing may be performed at additional charge.

• Mayo Autoimmune/Paraneoplastic Encephalopathy Evaluation Algorithm, Serum

Ordering Guidance: Refer to Autoimmune Encephalitis Testing Recommendations or consult the Laboratory Medicine Resident on-call.

• The Mayo Antibody Prevalence in Epilepsy and Encephalopathy (APE²) Scorecard may be used to determine the likelihood of neural antibody positivity in patients with encephalopathy and/or seizures.
• For a list of antibodies performed in each phenotype-specific autoimmune neurology panel, refer to the Mayo Autoimmune Neurology Antibody Matrix.

Ordering Requirements: Orders from UW Medicine Neurology Clinics are pre-approved. For all other orders, Laboratory Medicine Resident (LMR) approval is required.

***Note: Effective 10/13/26, the Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum profile will undergo the following component changes at Mayo Clinic Laboratories:

• Tests Added to Profile: AK5 IFA, GABA-A-R CBA, KLHL11 CBA, mGlur5 IFA, and Ma2
• Tests Removed from Profile: GFAP IFA, NIF IFA

Additional antibodies will be reported under the Encephalopathy Interpretation, Serum [RAEESI] component until a battery revision is completed on December 1st, 2026.***

Reference Values:

Note: Includes reference values for panel tests only.

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, CRMP-5-IgG, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

CRMP-5 titers lower than 1:240 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored serum (held 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 to request CRMP-5 Western blot.

Interpretation: Neuronal, glial, and muscle autoantibodies are valuable serological markers of autoimmune encephalopathy and of a patient's immune response to cancer. These autoantibodies are usually accompanied by subacute neurological symptoms and signs are not found in healthy subjects. It is not uncommon for more than 1 of the following autoantibody specificities to be detected in patients with an autoimmune encephalopathy:

• Plasma membrane autoantibodies: N-methyl-D-aspartate (NMDA) receptor; 2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid (AMPA) receptor; gamma-amino butyric acid (GABA-B) receptor; neuronal ACh receptor. These are all potential effectors of neurological dysfunction.

• Neuronal nuclear autoantibodies, type 1 (ANNA-1), type 2 (ANNA-2), or type 3 (ANNA-3)

• Neuronal or muscle cytoplasmic antibodies: amphiphysin, Purkinje cell antibodies (PCA-1) and PCA-2, CRMP-5, GAD65, or striational

Cautions:

Negative results do not exclude autoimmune encephalopathy or cancer.

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

Outside Laboratories: Centrifuge samples and transfer serum to a separate plastic vial. Refrigerate serum while awaiting shipment. Transport with a cold pack.

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 72 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, insufficient sample volume.

Centrifuge samples and transfer 4 mL serum (2.5 mL minimum) to a separate plastic aliquot. Refrigerate serum.

Sendouts:

• Order Mayo Test: ENS2
• Interfaced: Yes [Interface: 601; Worksheet: MARF]

Stability: Refrigerated (preferred): 28 days; Frozen: 28 days; Ambient: 72 hours.

Reject Due To: Gross hemolysis, gross lipemia, gross icterus, insufficient sample volume.