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Test Name:
Paraneoplastic Autoantibody Evaluation, Serum
- SBMF No:
42239 - Performance Lab Name:
Mayo Medical Laboratories - Test Mnemonic:
PAEVAL - ABN:
Required – Not FDA-Approved - CPT Code:
83519x5; 83520; 86256x9
If indicated, add; 83519 (AChR Modulating Ab); 84182 (Amphiphysin Western Blot); 84182 (CRMP-5-IgG Western Blot); 84182 (Paraneoplastic Ab Western Blot); 86255 (NMO-IgG); 86341 (GAD65 Ab) - LOINC Code:
19146-0 - Ref Lab Test No:
PAVAL | 83380 - Test Includes:
Anti-Neuronal Nuclear Ab, Type 1
Anti-Neuronal Nuclear Ab, Type 2
Anti-Neuronal Nuclear Ab, Type 3
Anti-Glial Nuclear Ab, Type 1
Purkinje Cell Cytoplasmic Ab Type 1
Purkinje Cell Cytoplasmic Ab Type 2
Purkinje Cell Cytoplasmc Ab Type Tr
Amphiphysin Ab
CRMP-5-IgG
Striational (Striated Muscle) Ab
P/Q-Type Calcium Channel Ab
N-Type Calcium Channel Ab
ACh Receptor (Muscle) Binding Ab
AChR Ganglionic Neuronal Ab
Neuronal (V-G) K+ Channel Ab
CRMP-5-IgG Western Blot (If Indicated)
GAD65 Ab Assay (If Indicated)
ACh Receptor (Muscle) Modulating Ab (If Indicated)
Paraneoplastic Autoantibody Western Blot (If Indicated)
Amphiphysin Western Blot (If Indicated)
NMO-IgG (If Indicated) - Also Known As:
Paraneoplastic Antibodies
Paraneoplastic Neurological Autoimmunity - Spec Type:
Serum - Spec Container:
Gold top (SST) or Red top (serum) tube - Pref Vol:
4.0 mL - Min Vol:
2.0 mL - Fasting:
No - Spec Collect:
Routine venipuncture - Spec Process:
Clot 30 minutes
Promptly centrifuge 15 minutes
Immediately transfer serum to separate plastic tube - Spec Store Transport:
Refrigerated - Spec Stability:
72 hours room temperature (20-30°C)
14 days refrigerated (2-8°C) - Spec Reject:
Plasma
Grossly hemolyzed, icteric, or lipemic specimen - Spec Remarks:
Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician - Methodology:
Indirect Immunofluorescence Assay (IFA)
Radioimmunoassay (RIA)
Enzyme Immunoassay (EIA)
Western Blot (WB) - Use:
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 - Clinical Significance:
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 (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 in this evaluation:
– Neuronal nuclear (ANNA-1, ANNA-2, ANNA-3)
– Anti-glial/neuronal nuclear (AGNA-1; aka 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 hyper-excitability. 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 Range:
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)
< 1:240NEURONAL 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
< 1:60CATION CHANNEL ANTIBODIES
N-Type Calcium Channel Antibody
< or = 0.03 nmol/L
P/Q-Type Calcium Channel Antibody
< or = 0.02 nmol/L
ACh Receptor (Muscle) Binding Antibody
< or = 0.02 nmol/L
AChR Ganglionic Neuronal Antibody
< or = 0.02 nmol/L
Neuronal VGKC Autoantibody
< or = 0.02 nmol/LNeuron-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."
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 1 paraneoplastic autoantibody to be detected, each predictive of the same cancer.Negative results do not exclude cancer.
The neuronal voltage-gated potassium channel antibody assay will not be performed for children (aged 18 years or younger) because normal values are not yet established for the pediatric population.
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 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.
Testing Algorithm:
– If IFA 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 is suggestive of neuromyelitis optica (NMO), NMO-IgG 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 ACh receptor binding antibody is > 0.02 or if striational antibodies are > or = 1:60, 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.
Reference:
"Paraneoplastic Autoantibody Evaluation, Serum." 2011 Online Test Catalog, Mayo Medical Laboratories, 2011. Web. 18 November 2011 <http://www.mayomedicallaboratories.com/test-catalog/Overview/83380> - Additional Test Info:
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. - Day Run:
Varies - Time Reported:
11-18 days - Test Type:
IMMUNOLOGY
