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HelpTest ID PAVAL Paraneoplastic Autoantibody Evaluation, Serum
Useful For
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
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PAINT | Interpretive Comments | No | Yes |
| ANN1S | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
| ANN2S | Anti-Neuronal Nuclear Ab, Type 2 | No | Yes |
| ANN3S | Anti-Neuronal Nuclear Ab, Type 3 | No | Yes |
| AGN1S | Anti-Glial Nuclear Ab, Type 1 | No | Yes |
| PCABP | Purkinje Cell Cytoplasmic Ab Type 1 | No | Yes |
| PCAB2 | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
| PCATR | Purkinje Cell Cytoplasmic Ab Type Tr | No | Yes |
| AMPHS | Amphiphysin Ab, S | No | Yes |
| CRMS | CRMP-5-IgG, S | No | Yes |
| STR | Striational (Striated Muscle) Ab, S | Yes | Yes |
| CCPQ | P/Q-Type Calcium Channel Ab | No | Yes |
| CCN | N-Type Calcium Channel Ab | No | Yes |
| ARBI | ACh Receptor (Muscle) Binding Ab | Yes | Yes |
| GANG | AChR Ganglionic Neuronal Ab, S | No | Yes |
| VGKC | Neuronal (V-G) K+ Channel Ab, S | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| GD65S | GAD65 Ab Assay, S | Yes | No |
| WBN | Paraneoplastic Autoantibody WBlot,S | No | No |
| CRMWS | CRMP-5-IgG Western Blot, S | No | No |
| ARMO | ACh Receptor (Muscle) Modulating Ab | No | No |
| ABLOT | Amphiphysin Western Blot, S | No | No |
| NMDCS | NMDA-R Ab CBA, S | No | No |
| AMPCS | AMPA-R Ab CBA, S | No | No |
| GABCS | GABA-B-R Ab CBA, S | No | No |
| NMDIS | NMDA-R Ab IF Titer Assay, S | No | No |
| AMPIS | AMPA-R Ab IF Titer Assay, S | No | No |
| GABIS | GABA-B-R Ab IF Titer Assay, S | No | No |
| NMOCS | NMO/AQP4-IgG CBA, S | Yes | No |
Testing Algorithm
If IFA (ANN1S, ANN2S, ANN3S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AGN1S) patterns are indeterminate, paraneoplastic autoantibody Western blot is performed at an additional charge.
If client requests or if IFA patterns suggest CRMP-5-IgG, CRMP-5-IgG Western blot is performed at an additional charge.
If IFA pattern suggest NMO/AQP4-IgG, NMO/AQP4-IgG CBA is performed at an additional charge.
If IFA patterns suggest amphiphysin antibody, amphiphysin Western blot is performed at an additional charge.
If IFA patterns suggest GAD65 antibody, GAD65 antibody radioimmunoassay is performed at an additional charge.
If IFA pattern suggest NMDA-R, NMDA-R Ab CBA and/or NMDA-R Ab IF Titer Assay is performed at an additional charge.
If IFA pattern suggest AMPA-R, AMPA-R Ab CBA and/or AMPA-R Ab IF Titer Assay is performed at an additional charge.
If IFA pattern suggest GABA-B-R, GABA-B-R Ab CBA and/or GABA-B-R Ab IF Titer Assay is performed at an additional charge.
If ACh receptor binding antibody is >0.02, ACh receptor modulating antibodies and CRMP-5-IgG Western blot are 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.
See Paraneoplastic Evaluation Algorithm in Special Instructions
Special Instructions
Method Name
ANN1S, ANN2S, ANN3S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AGN1S, AMPIS, NMDIS, GABIS: Indirect Immunofluorescence Assay (IFA)
STR: Enzyme Immunoassay (EIA)
CCPQ, CCN, ARBI, ARMO, GANG, VGKC: Radioimmunoassay (RIA)
WBN, CRMWS, ABLOT: Western Blot
NMOCS, NMDCS, AMPCS, GABCS: Cell-binding assay (CBA)
PAINT: Interpretive Comment
Reporting Name
Paraneoplastic Autoantibody Eval, SSpecimen Type
SerumContainer/Tube:
Preferred: Red top
Acceptable: Serum gel
Specimen Volume: 4 mL
Additional Information: Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.
General Request Form (T239) (http://www.mayomedicallaboratories.com/it-mmfiles/general-request-form.pdf)
Neurology Test Request Form (T732) (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)
Specimen Minimum Volume
2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Serum | Refrigerated (preferred) | 28 days |
| Frozen | 28 days | |
| Ambient | 72 hours |
Clinical Information
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
NEURONAL NUCLEAR ANTIBODIES
Antineuronal Nuclear Antibody-Type 1 (ANNA-1)
<1:240
Antineuronal Nuclear Antibody-Type 2 (ANNA-2)
<1:240
Antineuronal Nuclear Antibody-Type 3 (ANNA-3)
<1:240
Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)
<1:240
NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES
Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)
<1:240
Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)
<1:240
Purkinje Cell Cytoplasmic Antibody, Type Tr (PCA-Tr)
<1:240
Amphiphysin Antibody
<1:240
CRMP-5-IgG
<1:240
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 or 507-266-5700 to request CRMP-5 Western blot.
Striational (Striated Muscle) Antibodies
<1:120
CATION CHANNEL ANTIBODIES
N-Type Calcium Channel Antibody
≤0.03 nmol/L
P/Q-Type Calcium Channel Antibody
≤0.02 nmol/L
AChR Ganglionic Neuronal Antibody
≤0.02 nmol/L
Neuronal VGKC Autoantibody
≤0.02 nmol/L
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."
ACHR RECEPTOR ANTIBODIES
ACh Receptor (Muscle) Binding Antibody
≤0.02 nmol/L
AChR Receptor (Muscle) Modulating Antibody
0-20% loss of AChR
NEUROMYELITIS OPTICA (NMO)/AQUAPORIN-4-IGG CELL-BINDING ASSAY
Negative
Paraneoplastic Western Blot
Negative
CRMP-5-IgG Western Blot
Negative
Amphiphysin Western Blot
Negative
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
Cautions
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.
This test should not be requested for 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 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.
Day(s) Performed
ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, Amphiphysin, CRMP-5-IgG, NMDIS, AMPIS, GABIS: Monday through Thursday, Sunday; 12:00 p.m. and 5:00 p.m.
Striational (striated muscle) antibodies: Monday through Friday; 2:00 p.m.
P/Q-type calcium channel antibody, N-type calcium channel antibody: Monday through Friday; 6:00 a.m.
ACh receptor (muscle) binding antibody: Monday through Friday, Sunday; 2:00 p.m.
AChR ganglionic neuronal antibody, neuronal (V-G) K+ channel autoantibody: Sunday through Thursday; 10:00 p.m.
Paraneoplastic autoantibody Western blot, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday through Friday; 8:00 a.m.
GAD65 antibody assay: Monday through Friday; 2:00 a.m.
ACh receptor (muscle) modulating antibodies: Monday through Thursday, Saturday; 12:00 p.m.
NMO/AQP4-IgG CBA, NMDCS, AMPCS, GABCS: Monday through Friday; 4:00 a.m.
Report Available
10 days (negative)Performing Laboratory
Mayo Medical Laboratories in Rochester
Test Classification
This test was developed and its performance characteristics determined by Laboratory Medicine and Pathology, Mayo Clinic. This test has not been cleared or approved by the U.S. Food and Drug Administration.CPT Code Information
83519-ACh receptor (muscle) binding antibody
83519-AChR ganglionic neuronal antibody
83519-Neuronal VGKC autoantibody
83519-N-type calcium channel antibody
83519-P/Q-type calcium channel antibody
83520-Striational (striated muscle) antibodies
86255-AGNA-1
86255-Amphiphysin
86255-ANNA-1
86255-ANNA-2
86255-ANNA-3
86255-CRMP-5-IgG
86255-PCA-1
86255-PCA-2
86255-PCA-Tr
83519-ACh receptor (muscle) modulating antibodies (if appropriate)
84182-Amphiphysin Western blot (if appropriate)
84182-CRMP-5-IgG Western blot (if appropriate)
84182-Paraneoplastic autoantibody Western blot confirmation (if appropriate)
86255-NMO/AQP4-IgG CBA (if appropriate)
86255-AMPCS (if appropriate)
86255-GABCS (if appropriate)
86255-NMDCS (if appropriate)
86256-AMPIS (if appropriate)
86256-GABIS (if appropriate)
86256-NMDIS (if appropriate)
86341-GAD65 antibody assay (if appropriate)