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

Test ID: PAVAL    
Paraneoplastic, Autoantibody Evaluation, Serum

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

Serological 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

 

Monitoring the immune response of seropositive patients in the course of cancer therapy

 

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

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

 

If IFA patterns suggest ANNA-1 antibody, then ANNA-1 immunoblot is performed at an additional charge.

 

If IFA patterns suggest ANNA-2 antibody, then ANNA-2 immunoblot is performed at an additional charge.

 

If IFA patterns suggest PCA-1 antibody, then PCA-1 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 patterns suggest GAD65 antibody, then GAD65 antibody radioimmunoassay (RIA) is performed at an additional charge.

 

If IFA pattern suggest NMDA-receptor, then NMDA- receptor antibody cell-binding assay (CBA), and/or NMDA- receptor antibody titer is performed at an additional charge.

 

If IFA pattern suggest AMPA- receptor, then AMPA- receptor antibody CBA and/or AMPA- receptor antibody titer is performed at an additional charge.

 

If IFA pattern suggest GABA-B- receptor, then GABA-B- receptor antibody CBA and/or GABA-B- receptor antibody titer is performed at an additional charge.

 

If IFA pattern suggest DPPX, then DPPX antibody CBA and DPPX antibody titer is performed at an additional charge.

 

If IFA pattern suggest mGluR1, then mGluR1 antibody CBA and mGluR1 antibody titer is performed at an additional charge.

 

If VGKC is >0.00 nmol/L, then LGI1-IgG CBA and CASPR2-IgG CBA, S are performed at an additional charge.

 

If CRMP IFA is positive, then ACh receptor binding antibody, CRMP-5-IgG Western blot, and ACh receptor (muscle) modulating antibody will be performed at an additional charge.

 

If striational striated muscle antibody is 1:7,680 or greater, then ACh receptor binding antibody, CRMP-5-IgG Western blot, and ACh receptor (muscle) modulating antibody will be performed at an additional charge.

 

CRMP-5-IgG Western blot is also performed by specific request for more sensitive detection of CRMP-5-IgG. Testing should be requested in cases of subacute basal ganglionic disorders (chorea, Parkinsonism), cranial neuropathies (especially loss of vision, taste, or smell) and myelopathies.

 

The following algorithms are available in Special Instructions:

-Paraneoplastic Evaluation Algorithm

-Hereditary Peripheral Neuropathy Diagnostic Algorithm

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, 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. 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 in this evaluation:

-Neuronal nuclear (ANNA-1, ANNA-2, ANNA-3)

-Anti-glial/neuronal nuclear (AGNA-1; also known as Sox1)

-Neuronal and muscle cytoplasmic (PCA-1, PCA-2, PCA-Tr, CRMP-5, amphiphysin, and striational)

-Plasma membrane cation channel, calcium channels, P/Q-type and N-type calcium channel, dendrotoxin-sensitive potassium channels, and neuronal (ganglionic) and muscle nicotinic acetylcholine receptors (AChR). These autoantibodies are potential effectors of neurological dysfunction.

 

Seropositive patients usually present with subacute neurological symptoms and signs such as encephalopathy; cerebellar ataxia; myelopathy; radiculopathy; plexopathy; or sensory, sensorimotor, or autoimmune neuropathy, with or without a neuromuscular transmission disorder: Lambert-Eaton syndrome, 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 or environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less neurological morbidity and offer the best hope for survival.

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

GANG

AChR Ganglionic Neuronal Ab, S

Radioimmunoassay (RIA)

< or =0.02 nmol/L

AMPHS

Amphiphysin Ab, S

Immunofluorescence (IFA)

<1:240

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

<1:240

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

<1:240

ANN2S

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:240

ANN3S

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:240

CRMS

CRMP-5-IgG, S

IFA

<1:240

VGKC

Neuronal (V-G) K+ Channel Ab, S

RIA

< or =0.02 nmol/L

CCN

N-Type Calcium Channel Ab

RIA

< or =0.03 nmol/L

CCPQ

P/Q-Type Calcium Channel Ab

RIA

< or =0.02 nmol/L

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:240

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:240

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

STR

Striational (Striated Muscle) Ab, S

Enzyme-linked immunosorbent assay (ELISA)

<1:120

 

Reflex Tests:

Test ID

Reporting name

Methodology

Reference value

ARBI

ACh Receptor (Muscle) Binding Ab

RIA

< or =0.02 nmol/L

ARMO

ACh Receptor (Muscle) Modulating Ab

Live cell assay (LCA)

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

AGNBS

AGNA-1 Immunoblot, S

Immunoblot (IB)

Negative

AMPCS

AMPA-R Ab CBA, S

Cell-binding assay (CBA)

Negative

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

AMIBS

Amphiphysin Immunoblot, S

IB

Negative

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMWS

CRMP-5-IgG Western Blot, S

Western blot

Negative

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPIS

DPPX Ab IFA, S

IFA

Negative

DPPTS

DPPX Ab IFA Titer, 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

RIA

< or =0.02 nmol/L

Reference values apply to all ages

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

GL1TS

mGluR1 Ab IFA Titer, 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

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

 

Neuron-restricted patterns of IgG staining that do not fulfill criteria for amphiphysin, ANNA-1, ANNA-2, ANNA-3, AGNA-1, 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, cranial neuropathy, and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 to request CRMP-5 Western blot.

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. Conversely, a positive autoantibody profile has 80% to 90% predictive value for a specific cancer. It is not uncommon for more than one 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

Negative results do not exclude cancer.

 

This evaluation does not include Ma2 autoantibody (alias: MaTa). Ma2 autoantibody has been described in patients with brainstem and limbic encephalitis in the context of testicular germ cell neoplasms. Scrotal ultrasound is advisable in men who present with unexplained subacute encephalitis. N-methyl-D-asparate receptor antibodies have been reported in women with paraneoplastic encephalitis related to ovarian teratoma.

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

1. McKeon A, Pittock SJ: Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 2011;122:381-400

2. Horta ES, Lennon VA, Lachance DH, et al: Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res 2014;20:3862-3869

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