TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: AIAES    
Autoimmune Axonal Evaluation, Serum

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

Evaluation of patients who present with a subacute neurological disorder of undetermined etiology, especially those with known risk factors for cancer

 

Directing a focused search for cancer

 

Investigating neurological symptoms that appear in the course of, or after, cancer therapy, and are not explainable by metastasis

 

Differentiating autoimmune neuropathies from neurotoxic effects of chemotherapy

 

Detecting early evidence of cancer recurrence in previously seropositive patients

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

If indirect immunofluorescence assay (IFA) patterns suggest antiglial nuclear antibody-1 (AGNA-1) antibody, then AGNA-1 antibody immunoblot is performed at an additional charge.

 

If IFA patterns suggest antineuronal nuclear antibodies (ANNA)-1, then ANNA-1 immunoblot and ANNA-2 immunoblot are performed at an additional charge.

 

If IFA patterns suggest ANNA-2 antibody, then ANNA-2 immunoblot, ANNA-1 immunoblot, and ANNA-2 antibody IFA are performed at an additional charged.

 

If IFA patterns suggest glutamic acid decarboxylase-65 (GAD65) antibody, then GAD65 radioimmunoassay is performed at an additional charge.

 

If IFA patterns suggest Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 antibody immunoblot is performed at an additional charge.

 

If IFA patterns suggest PCA-Tr antibody, then PCA-Tr immunoblot is performed at an additional charge.

 

If IFA pattern suggests amphiphysin antibody, then amphiphysin antibody immunoblot is performed at an additional charge.

 

If IFA pattern suggests dipeptidyl-peptidase-like protein-6 antibody (DPPX) antibody, then DPPX antibody cell-binding assay (CBA) and DPPX antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1antibody CBA and mGluR1 antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then GFAP antibody CBA and GFAP antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests N-methyl-D-aspartate receptor (NMDAR) antibody, then NMDAR antibody CBA and NMDAR antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-R) antibody, then AMPA-R antibody CBA and AMPA-R antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B receptor (GABA-B-R) antibody, then GABA-B-R antibody CBA and GABA-B-R antibody IFA titer are performed at an additional charge.

 

See Autoimmune Axonal Evaluation Algorithm in Special Instructions.

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

Neuropathy patients have variable sensory disturbance (loss or exaggerated sensation) with pain, weakness, and autonomic involvements such as sweat abnormalities, gastrointestinal dysfunction, and lightheadedness on standing. These symptoms are as a result of injury to the distal nerves, roots, ganglia or their gathering points (nerve plexus in the thighs and arms). Patients may have symmetric or asymmetric involvements of the extremities, trunk, and head including extraocular muscles. Subacute onsets and asymmetric involvements favor inflammatory or immune causes over inherited or metabolic forms. Depending on the specific inflammatory or immune mediated causes other parts of the nervous system may also be affected (brain, cerebellum, spinal cord).

 

In the evaluation of patients with immune mediated autoantibody neuropathies, nerve conduction studies and needle electromyography can help to classify the neuropathy as either: 1) primary axonal; 2) primary demyelinating; or 3) mixed axonal and demyelinating. This evaluation focuses on persons with primary axonal forms.

 

Well established neuronal autoantibodies responsible for axonal neuropathies include: antineuronal nuclear antibodies (ANNA1 and 3), Purkinje cytoplasmic antibody (PCA1 and 2), amphiphysin antibody, collapsin response mediator protein 5 (CRMP5) antibody, leucine-rich glioma inactivated 1 protein (LGI1) antibody, and contactin-associated response protein 2 (CASPR2) antibody. Other autoantibodies have preliminary evidence to support their association with neuropathy including: alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) antibody, antiglial nuclear antibody (AGNA); antineuronal nuclear type 2 antibody (ANNA2), gamma-aminobutyric acid B receptor (GABABR) antibody, glutamic acid decarboxylase 65 (GAD65) receptor antibody, glial fibrillary acidic protein (GFAP) antibody, N-methyl-D-aspartate receptor (NMDAR) antibody, Purkinje cell cytoplasmic Tr (PCA-Tr) antibody, dipeptidyl-peptidase-like protein-6 (DPPX) antibody, and metabotropic glutamate receptor 1 (mGluR1).

 

A patient's humoral and cellular immune response leads to the neurological syndrome. This may be related to an underlying cancer or unidentified antigen trigger. If related to cancer it may be a new or recurrent malignancy, 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, glia, or muscle are generated in this immune response and serve as serological markers of paraneoplastic autoimmunity. Cancers recognized in this context most commonly are small-cell lung carcinoma, thymoma, ovarian (or related Mullerian) carcinoma, breast carcinoma, and Hodgkin lymphoma. Pertinent childhood neoplasms recognized thus far include neuroblastoma, thymoma, Hodgkin lymphoma, and chondroblastoma.

 

This evaluation focuses on those antibodies with known associations with varied forms of peripheral axonal neuropathy. Seropositive patients usually present with subacute neurological symptoms of radiculopathy; plexopathy; or sensory, sensorimotor, or autonomic neuropathy, with or without a neuromuscular transmission disorder such as neuromuscular hyperexcitability. Other peripheral manifestation includes cranial neuropathies, especially loss of vision, hearing, smell, or taste. Commonly beyond the peripheral manifestation are encephalopathy, seizures, cerebellar ataxia, and myelopathy. 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, and limbic encephalopathy.

 

Cancer risk factors include past or family history of cancer, history of smoking, or social or environmental exposure to carcinogens.

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.

Test ID

Reporting name

Methodology

Reference value

AIAEI

Autoimmune Axonal Interp, S

Interpretation

NA

AGN1S

Anti-Glial Nuclear Ab, Type 1

Indirect Immunofluorescence  (IFA)

<1:240

AMPHS

Amphiphysin Ab, S

IFA

<1:240

ANN1S

ANNA-1, S

IFA

<1:240

ANN3S

ANNA-3, S

IFA

<1:240

CRMS

CRMP-5-IgG, S

IFA

<1:240

CRMWS

CRMP-5-IgG Western Blot, S

Western Blot (WB)

Negative (reported as positive or negative)

CS2CS

CASPR2-IgG CBA, S

Cell Binding Assay (CBA)

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

PCAB2

PCA-2, S

IFA

<1:240

PCABP

PCA-1, S

IFA

<1:240

 

Reflex Information:

Test ID

Reporting name

Methodology

Reference value

AGNBS

AGNA-1 Immunoblot, S

Immunoblot (IB)

Negative

AMIBS

Amphiphysin Immunoblot, S

IB

Negative

AMPCS

AMPA-R Ab CBA, S

CBA

Negative

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

ANN2S

ANNA-2, S

IFA

<1:240

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPTS

DPPX Ab IFA, S

IFA

<1:240

GABCS

GABA-B-R Ab CBA, S

CBA

Negative

GABIS

GABA-B-R Ab IF Titer Assay, S

IFA

<1:120

GD65S

GAD65 Ab Assay, S

Radioimmunoassay (RIA)

<0.02 nmol/L

Reference values apply to all ages

GFACS

GFAP CBA, S

CBA

Negative

GFATS

GFAP IFA Titer, S

IFA

<1:240

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1TS

mGluR1 Ab IFA, S

IFA

<1:240

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

NMDIS

NMDA-R Ab IF Titer Assay, S

IFA

<1:120

PC1BS

PCA-1 Immunoblot, S

IB

Negative

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

 

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."

Interpretation Provides information to assist in interpretation of the test results

Antibodies directed at onconeural proteins shared by neurons, glia, 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 autoantibody predicts a specific neurological syndrome. More than one paraneoplastic autoantibody may be detected and associated with specific cancers.

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

Negative results do not exclude the possibility of a cancer diagnosis.

 

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

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Klein CJ: Autoimmune-mediated peripheral neuropathies and autoimmune pain. In: Pittock SJ, Vincent A, eds. Handbook of Clinical Neurology; Autoimmune Neurology. Elsevier; 2016:417-446

2. Cutsforth-Gregory JK, McKeon A, Coon EA, et al: Ganglionic antibody level as a predictor of severity of autonomic failure. Mayo Clin Proc. 2018;93:1440-1447

3. Wei YC, Huang CC, Liu CH, Kuo HC, Lin JJ: Peripheral neuropathy in limbic encephalitis with anti-glutamate receptor antibodies: Case report and systematic literature review. Brain Behav. 2017;7:e00779

4. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncologic profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998;50:652-657

5. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol. 2003;53:580-587

6. Chan KH, Vernino S, Lennon VA: ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol. 2001;50:301-311

7. Dubey D, Lennon VA, Gadoth A, et al. Autoimmune CRMP5 neuropathy phenotype and outcome defined from 105 cases. Neurology. 2018;90:e103-e110

8. Gadoth A, Pittock SJ, Dubey D, et al: Expanded phenotypes and outcomes among 256 LGI1/CASPR2-IgG-positive patients. Ann Neurol. 2017;82:79-92

9. Honnorat J, Trouillas P, Thivolet C, Aguera M, Belin MF: Autoantibodies to glutamate decarboxylase in a patient with cerebellar cortical atrophy, peripheral neuropathy, and slow eye movements. Arch Neurol. 1995;52:462-468

10. McKeon A, Tracy JA: GAD65 neurological autoimmunity. Muscle Nerve. 2017;56:15-27

11. Bradshaw MJ, Haluska P, McKeon A, Klein CJ: Multifocal neuropathy as the presenting symptom of Purkinje cell cytoplasmic autoantibody-1. Muscle Nerve. 2013;48:827-831

12. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005;58:96-107

Special Instructions Library of PDFs including pertinent information and forms related to the test