Home
HelpTest ID: PAVAL Paraneoplastic, Autoantibody Evaluation, Serum
Reporting Name
Paraneoplastic Autoantibody Eval, SUseful 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 during, 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 during cancer therapy
Detecting early evidence of cancer recurrence in previously seropositive patients
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:
-Antineuronal nuclear antibodies (ANNA-1, ANNA-2, ANNA-3)
-Anti-glial/neuronal nuclear antibodies (AGNA-1; also known as Sox1)
-Neuronal and muscle cytoplasmic antibodies (Purkinje cytoplasmic antibody [PCA]-1, PCA-2, PCA-Tr, collapsin response-mediator protein [CRMP]-5, and amphiphysin)
-Plasma membrane cation channel, P/Q-type calcium channel, and dendrotoxin-sensitive potassium channels. These autoantibodies are potential effectors of neurological dysfunction.
Patients who are seropositive usually present with subacute neurological signs and symptoms, 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 previous 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.
Interpretation
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.
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PAINT | Interpretive Comments | No | Yes |
| AMPHS | Amphiphysin Ab, S | No | Yes |
| AGN1S | Anti-Glial Nuclear Ab, Type 1 | 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 |
| CRMS | CRMP-5-IgG, S | No | Yes |
| VGKC | Neuronal (V-G) K+ Channel Ab, S | No | Yes |
| CCPQ | P/Q-Type Calcium Channel Ab | 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 |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| AGNBS | AGNA-1 Immunoblot, S | No | No |
| AMIBS | Amphiphysin Immunoblot, S | No | No |
| AN1BS | ANNA-1 Immunoblot, S | No | No |
| AN2BS | ANNA-2 Immunoblot, S | No | No |
| CS2CS | CASPR2-IgG CBA, S | No | No |
| CRMWS | CRMP-5-IgG Western Blot, S | Yes | No |
| LG1CS | LGI1-IgG CBA, S | No | No |
| PC1BS | PCA-1 Immunoblot, S | No | No |
| PCTBS | PCA-Tr Immunoblot, S | No | No |
| AGNTS | AGNA-1 Titer, S | No | No |
| APHTS | Amphiphysin Ab Titer, S | No | No |
| AN1TS | ANNA-1 Titer, S | No | No |
| AN3TS | ANNA-3 Titer, S | No | No |
| CRMTS | CRMP-5-IgG Titer, S | No | No |
| PC1TS | PCA-1 Titer, S | No | No |
| PC2TS | PCA-2 Titer, S | No | No |
| PCTTS | PCA-Tr Titer, S | No | No |
| AN2TS | ANNA-2 Titer, S | No | No |
Testing Algorithm
If the immunofluorescence assay (IFA) patterns suggest antiglial nuclear antibody-1 (AGNA-1) antibody, then AGNA-1 immunoblot and AGNA-1 IFA titer will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot and amphiphysin IFA titer will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then ANNA-1 immunoblot (IB), ANNA-1 IFA titer, and ANNA-2 IB will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then ANNA-2 IB, ANNA-2 IFA titer, and ANNA-1 IB will be performed at an additional charge.
If the IFA pattern suggests ANNA-3 antibody, then ANNA-3 IFA titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1) antibody, then PCA-1 IB and PCA-1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr IB and PCA-Tr IFA titer will be performed at an additional charge.
If voltage-gated potassium channel (VGKC) is above 0.00 nmol/L, then leucine-rich, glioma inactivated 1 (LGI1)-IgG cell-binding assay (CBA) and contactin-associated protein-like 2 (CASPR2)-IgG will be performed at an additional charge.
If the collapsin response-mediator protein (CRMP) IFA is positive, then CRMP-5-IgG Western blot and CRMP-5-IgG IFA titer 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:
Report Available
10 to 17 daysDay(s) Performed
Profile tests: Monday through Sunday; Reflex tests: Varies
Clinical Reference
1. McKeon A, Pittock SJ: Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol. 2011 Oct;122(4):381-400
2. Horta ES, Lennon VA, Lachance DH, et al: Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014 Jun;20(14):3862-3869
Method Name
PAINT: Medical Interpretation
AGN1S, AGNTS, AMPHS, APHTS, ANN1S, ANN2S, ANN3S, AN2TS, AN3TS, CRMS, CRMTS, PCABP, PC1TS, PCAB2, PC2TS, PCATR, PCTTS, AN1TS: Indirect Immunofluorescence Assay (IFA)
CCPQ, VGKC: Radioimmunoassay (RIA)
CRMWS: Western Blot (WB)
AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)
CS2CS, LG1CS: Cell-Binding Assay (CBA)
Specimen Type
SerumOrdering Guidance
This test no longer contains all known, clinically relevant antibodies for patients suspected of autoimmune neurological disorders. Instead, consider a comprehensive neurological phenotype-specific autoimmune/paraneoplastic evaluation (eg, encephalopathy, movement disorders, myelopathy, axonal neuropathy). For more information as well as phenotype-specific testing options, refer to Autoimmune Neurology Test Ordering Guide or the Neurology specialty website.
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.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering provider name, phone number, mailing address, and e-mail address
Specimen Required
Patient Preparation: For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 4 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Specimen Minimum Volume
2 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 28 days | |
| Frozen | 28 days | ||
| Ambient | 72 hours |
Special Instructions
Reference Values
|
Test ID |
Reporting name |
Methodology* |
Reference value |
|
PAINT |
Interpretive Comments |
Medical interpretation |
Not applicable |
|
AMPHS |
Amphiphysin Ab, S |
IFA |
Negative |
|
AGN1S |
Anti-Glial Nuclear Ab, Type 1 |
IFA |
Negative |
|
ANN1S |
Anti-Neuronal Nuclear Ab, Type 1 |
IFA |
Negative |
|
ANN2S |
Anti-Neuronal Nuclear Ab, Type 2 |
IFA |
Negative |
|
ANN3S |
Anti-Neuronal Nuclear Ab, Type 3 |
IFA |
Negative |
|
CRMS |
CRMP-5-IgG, S |
IFA |
Negative |
|
VGKC |
Neuronal (V-G) K+ Channel Ab, S |
RIA |
≤0.02 nmol/L |
|
CCPQ |
P/Q-Type Calcium Channel Ab |
RIA |
≤0.02 nmol/L |
|
PCABP |
Purkinje Cell Cytoplasmic Ab Type 1 |
IFA |
Negative |
|
PCAB2 |
Purkinje Cell Cytoplasmic Ab Type 2 |
IFA |
Negative |
|
PCATR |
Purkinje Cell Cytoplasmic Ab Type Tr |
IFA |
Negative |
Reflex Tests:
|
Test ID |
Reporting name |
Methodology* |
Reference value |
|
AGNBS |
AGNA-1 Immunoblot, S |
IB |
Negative |
|
AGNTS |
AGNA-1 Titer, S |
IFA |
<1:240 |
|
AMIBS |
Amphiphysin Immunoblot, S |
IB |
Negative |
|
AN1BS |
ANNA-1 Immunoblot, S |
IB |
Negative |
|
AN1TS |
ANNA-1 Titer, S |
IFA |
<1:240 |
|
AN2BS |
ANNA-2 Immunoblot, S |
IB |
Negative |
|
AN2TS |
ANNA-2 Titer, S |
IFA |
<1:240 |
|
AN3TS |
ANNA-3 Titer, S |
IFA |
<1:240 |
|
APHTS |
Amphiphysin Ab Titer, S |
IFA |
<1:240 |
|
CRMTS |
CRMP-5-IgG Titer, S |
IFA |
<1:240 |
|
CS2CS |
CASPR2-IgG CBA, S |
CBA |
Negative |
|
CRMWS |
CRMP-5-IgG Western Blot, S |
WB |
Negative |
|
LG1CS |
LGI1-IgG CBA, S |
CBA |
Negative |
|
PC1BS |
PCA-1 Immunoblot, S |
IB |
Negative |
|
PC1TS |
PCA-1 Titer, S |
IFA |
<1:240 |
|
PC2TS |
PCA-2 Titer, S |
IFA |
<1:240 |
|
PCTBS |
PCA-Tr Immunoblot, S |
IB |
Negative |
|
PCTTS |
PCA-Tr Titer, S |
IFA |
<1:240 |
*Methodology abbreviations:
Immunofluorescence assay (IFA)
Cell-binding assay (CBA)
Western blot (WB)
Radioimmunoassay (RIA)
Immunoblot (IB)
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: 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 800-533-1710 to request CRMP-5 Western blot.
Test Classification
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.CPT Code Information
83519
86596
86255 x 9
84182-AGNBS (if appropriate)
86256-AGNTS (if appropriate)
84182-AMIBS (if appropriate)
86256-APHTS (if appropriate)
84182-AN1BS (if appropriate)
86256 AN1TS (if appropriate)
84182-AN2BS (if appropriate)
86256 AN2TS (if appropriate)
86256 AN3TS (if appropriate)
86256 CRMTS (if appropriate)
86255-CS2CS (if appropriate)
84182-CRMWS (if appropriate)
86255-LG1CS (if appropriate)
84182-PC1BS (if appropriate)
86256 PC1TS (if appropriate)
86256 PC2TS (if appropriate)
84182-PCTBS (if appropriate)
86256 PCTTS (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PAVAL | Paraneoplastic Autoantibody Eval, S | 43104-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 89080 | AGNA-1, S | 84927-3 |
| 81722 | Amphiphysin Ab, S | 72327-0 |
| 80150 | ANNA-1, S | 33615-6 |
| 80776 | ANNA-2, S | 43187-4 |
| 83137 | ANNA-3, S | 43102-3 |
| 81185 | P/Q-Type Calcium Channel Ab | 94349-8 |
| 83077 | CRMP-5-IgG, S | 72504-4 |
| 29347 | Interpretive Comments | 57771-8 |
| 83138 | PCA-2, S | 84925-7 |
| 9477 | PCA-1, S | 84924-0 |
| 83076 | PCA-Tr, S | 84926-5 |
| 89165 | Neuronal (V-G) K+ Channel Ab, S | 97560-7 |
| 618905 | IFA Notes | 48767-8 |
mml-Behavioral, mml-Epilepsy, mml-Movement-Disorders, mml-Demyelinating-Diseases, mml-Neuroimmunology, mml-Neuromuscular, mml-Neuro-oncology, mml-Pediatric, mml-Pain, mml-Spinal-Cord, mml-Neuro-ophthalmology, mml-Neuroimmunology-Evals