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HelpTest Code Epic LAB3220 Paraneoplastic, Autoantibody Evaluation, Serum
Additional Codes
SQ code PAVAL
Mayo code PAVAL
Reporting Name
Paraneoplastic Autoantibody Eval, SSpecimen Type
SerumPerforming Laboratory
Mayo Clinic Laboratories in Rochester
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 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
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:
Ordering 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.
Day(s) Performed
Profile tests: Monday through Sunday; Reflex tests: Varies
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 |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
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)
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 |
Method Description
Indirect Immunofluorescence Assay:
The patient's specimen is tested by a standardized indirect immunofluorescence assay (IFA) that uses a composite frozen section of mouse cerebellum, kidney, and gut tissues. After incubation with specimen and washing, fluorescein-conjugated goat-antihuman IgG is applied. Neuron-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Samples that are scored positive for any neuronal nuclear or cytoplasmic autoantibody are titrated to an endpoint. Interference by coexisting non-neuron-specific autoantibodies can usually be eliminated by serologic absorption.(Honorat JA, Komorowski L, Josephs KA, et al: IgLON5 antibody: neurological accompaniments and outcomes in 20 patients. Neurol Neuroimmunol Neuroinflamm. 2017 Jul 18;4(5):e385. doi: 10.1212/NXI.0000000000000385
Radioimmunoassay:
(125)I-labeled recombinant human antigens or labeled receptors are incubated with patient sample. After incubation, anti-human IgG is added to form an immunoprecipitate. The amount of (125)I-labeled antigen in the immunoprecipitate is measured using a gamma-counter. The amount of gamma emission in the precipitate is proportional to the amount of antigen-specific IgG in the sample. Results are reported as units of precipitated antigen (nMol) per L of patient sample.(Vernino S, Kryzer TJ, Lennon AV: Autoimmune autonomic neuropathy and neuromuscular hyperexcitability disorders. In: Rose NR, Hamilton RG, Detrick B, eds. Manual of Clinical and Laboratory Immunology. 6th ed. ASM Press; 2002:1013-1017; Jones AL, Flanagan EP, Pittock SJ, et al. Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol. 2015;72[11]:1304-1312 doi:10.1001/jamaneurol.2015.2378)
Cell-Binding Assay:
Patient serum is applied to a composite slide containing transfected and nontransfected HEK-293 cells. After incubation and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the presence of patient IgG binding.(Package insert: IIFT: Neurology Mosaics, Instructions for the indirect immunofluorescence test. EUROIMMUN; FA_112d-1_A_UK_C13, 02/2019)
Immunoblot:
All steps are performed at room temperature (18-28° C) utilizing the EUROBlot One instrument. Diluted patient serum (1:101) is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive serums will bind to the purified recombinant antigen, and negative serums will not bind. Strips are washed to remove unbound serum antibodies and then incubated with anti-human IgG antibodies (alkaline phosphatase-labelled) and incubated for 30 minutes. The strips are again washed to remove unbound anti-human IgG antibodies, and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produce a black band. Strips are digitized via picture capture on the EUROBlot One instrument and evaluated with the EUROLineScan software.(O'Connor K, Waters P, Komorowski L, et al. GABAA receptor autoimmunity: A multicenter experience. Neurol Neuroimmunol Neuroinflamm. 2019;6[3]:e552. doi:10.1212/NXI.0000000000000552)
Western Blot:
Neuronal antigens extracted aqueously from adult rat cerebellum, full-length recombinant human collapsin response-mediator protein-5 (CRMP-5), or full-length recombinant human amphiphysin protein is denatured, reduced, and separated by electrophoresis on 10% polyacrylamide gel. IgG is detected autoradiographically by enhanced chemiluminescence. (Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 Feb;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al: Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019;93(20):e1873-e1880. doi:10.1212/WNL.0000000000008472)