Test Catalog

Interpretive Handbook

Test 84300 :
Neuroimmunology Antibody Follow-up, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer. The cancer may be new or recurrent, is usually limited in metastatic volume, and is often occult by standard imaging procedures. Autoantibodies specific for onconeural proteins found in the plasma membrane, cytoplasm, and nucleus of neurons or muscle are generated in this immune response and serve as serological markers of paraneoplastic autoimmunity. The most commonly recognized cancers in this context are small-cell lung carcinoma (SCLC), thymoma, ovarian (or related mullerian) carcinoma, breast carcinoma, and Hodgkin's lymphoma. Pertinent childhood neoplasms recognized thus far include neuroblastoma, thymoma, Hodgkin's lymphoma, and chondroblastoma. An individual patient's autoantibody profile can predict a specific neoplasm with 90% certainty, but not the neurological syndrome.


Four classes of autoantibodies are recognized:

-Neuronal nuclear (antineuronal nuclear antibody-type 1 [ANNA-1], ANNA-2, ANNA-3)

-Neuronal and muscle cytoplasmic (Purkinje cell cytoplasmic antibody, type 1 [PCA-1], PCA-2, PCA-Tr, CRMP-5, amphiphysin, and striational)

-Glial nuclear (anti-glial nuclear antibody)

-Plasma membrane cation channel Antibodies (neuronal P/Q-type and N-type calcium channel and muscle acetylcholine receptor autoantibodies). These autoantibodies are potential effectors of neurological dysfunction.


Seropositive patients usually present with subacute neurological symptoms and signs. The patient may present with encephalopathy, cerebellar ataxia, myelopathy, radiculopathy, plexopathy, sensory, sensorimotor, or autonomic neuropathy, with or without coexisting evidence of a neuromuscular transmission disorder: Lambert-Eaton syndrome (LES), myasthenia gravis, or neuromuscular hyperexcitability. Initial signs may be subtle, but a subacute multifocal and progressive syndrome usually evolves. Sensorimotor neuropathy and cerebellar ataxia are common presentations, but the clinical picture in some patients is dominated by striking gastrointestinal dysmotility, limbic encephalopathy, basal ganglionitis, or cranial neuropathy (especially loss of vision, hearing, smell, or taste). Cancer risk factors include past or family history of cancer, history of smoking or social/environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less neurological morbidity and offer the best hope for survival.

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring patients who have previously tested positive for 1 or more antibodies in a Neuroimmunology Laboratory evaluation

Interpretation Provides information to assist in interpretation of the test results

Antibodies directed at onconeural proteins shared by neurons, muscle, and certain cancers are valuable serological markers of a patient's immune response to cancer. They are not found in healthy subjects and are usually accompanied by subacute neurological symptoms and signs. Several autoantibodies have a syndromic association, but no known autoantibody predicts a specific neurological syndrome. Conversely, a positive autoantibody profile has 80% to 90% predictive value for a specific cancer. It is not uncommon for more than 1 paraneoplastic autoantibody to be detected, each predictive of the same cancer.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test should only be utilized when the presence of paraneoplastic autoantibodies has been previously documented.


This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held one week and assayed if sufficiently decayed, or canceled if radioactivity remains.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.


Antineuronal Nuclear Antibody-Type 1 (ANNA-1)


Antineuronal Nuclear Antibody-Type 2 (ANNA-2)  


Antineuronal Nuclear Antibody-Type 3 (ANNA-3)




Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)


Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)


Purkinje Cell Cytoplasmic Antibody, Type Tr (PCA-Tr)


Amphiphysin Antibody






Paraneoplastic Autoantibody Western Blot Confirmation


CRMP-5-IgG Western Blot


Amphiphysin Western Blot





N-Type Calcium Channel Antibody

< or =0.03 nmol/L

P/Q-Type Calcium Channel Antibody

< or =0.02 nmol/L

AChR Ganglionic Neuronal Antibody

< or =0.02 nmol/L

Neuronal VGKC Autoantibody

< or =0.02 nmol/L



ACh Receptor (Muscle) Modulating Antibodies

0-20% (reported as __% loss of AChR)


N-Methyl-D-aspartate receptor (NMDA-R)

CBA: Negative

IFA: <1:120

2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl) propanoic acid receptor (AMPA-R)

CBA: Negative

IFA: <1:120

Gamma-Amino Butyric acid-type B receptor (GABA-B-R)

CBA: Negative

IFA: <1:120


Neuron-restricted patterns of IgG staining that do not fulfill criteria for amphiphysin, ANNA-1, ANNA-2, ANNA-3, PCA-1, PCA-2, PCA-Tr, or CRMP-5-IgG may be reported as "unclassified antineuronal IgG." Complex patterns that include non-neuronal elements may be reported as "uninterpretable."

Note: 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, and cranial neuropathy and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 or 507-266-5700 to request CRMP-5 Western blot.

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