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HELPFUL LINKS!

 

LAB COMMUNICATIONS 

 

COLLECTION & HANDLING

 

SPECIMEN TRANSPORTATION

Please call 616.774.7721 for specimen pick up

 

GENERAL INFORMATION

 

GENERAL TEST INFORMATION

 

BILLING

 

WEBSITES

Mayo Clinic Laboratories

Epic Code LAB10022 Paraneoplastic, Autoantibody Evaluation, Serum

Additional Codes

Mayo Code: PAVAL

Interface Order Alias: 11090

Epic Code: LAB 10022

Cerner: 9095

Performing 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

Specimen Type

Serum


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 healthcare professional's name, phone number, mailing address, and email address



Specimen Required


Patient Preparation: For optimal antibody detection, specimen collection is recommended before starting immunosuppressant medication or intravenous immunoglobulin (IVIg) 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.


Laboratory Test Directory | West Note:

COLLECTION NOTE: Volumes listed are in serum or plasma, draw approximately 2 1/2 times the requested volume in whole blood.

Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time
Serum Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

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

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

CRMWS

CRMP-5-IgG Western Blot, S

WB

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)

Western blot (WB)

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.

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. It should be noted that this evaluation is considered to be limited and not comprehensive (see Cautions).

 

Three 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 glial cytoplasmic antibodies (Purkinje cytoplasmic antibody [PCA]-1, PCA-2, PCA-Tr, collapsin response-mediator protein [CRMP]-5, and amphiphysin)

 

Patients who are seropositive usually present with subacute neurological signs and symptoms such as encephalopathy, cerebellar ataxia, myelopathy, nerve (including radiculopathy, plexopathy, sensory/sensorimotor, or autonomic) or neuromuscular junction disorders. Initial signs may be subtle, but a subacute multifocal and progressive syndrome usually evolves.

 

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.

Cautions

Negative results do not exclude cancer.

 

Intravenous immunoglobulin (IVIg) treatment prior to specimen collection may cause a false-positive result.

 

Immunosuppressive treatments, including plasma exchange, may lead to false-negative results.

 

This evaluation does not include a broad number of antibodies pertinent to autoimmune neurological disorders, paraneoplastic and idiopathic autoimmune. Use of phenotype specific evaluations is recommended rather than the paraneoplastic evaluation (eg, autoimmune encephalopathy evaluation for suspected autoimmune encephalitis, or autoimmune movement disorders evaluation for suspected autoimmune ataxia). In particular, several high and medium risk paraneoplastic antibodies are not included such as AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor IgG, gamma-aminobutyric acid (GABA) B receptor IgG, kelch-like protein 11- (KLHL11) IgG, Ma2-IgG, and N-methyl-D-aspartate (NMDA) receptor-IgG, among others.

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 signs and symptoms. 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.

Reporting Name

Paraneoplastic Autoantibody Eval, S

Method Name

PAINT: Technical Interpretation

 

AGN1S, AGNTS, AMPHS, APHTS, ANN1S, ANN2S, ANN3S, AN2TS, AN3TS, CRMS, CRMTS, PCABP, PC1TS, PCAB2, PC2TS, PCATR, PCTTS, AN1TS: Indirect Immunofluorescence Assay (IFA)

 

CRMWS: Western Blot (WB)

 

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS: Immunoblot (IB)

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;4(5):e385. doi:10.1212/NXI.0000000000000385)

 

Immunoblot:

All steps are performed at room temperature (18-28° C) utilizing the EUROBlot One instrument. Diluted patient sample (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 samples will bind to the purified recombinant antigen, and negative samples will not bind. Strips are washed to remove unbound antibodies and then incubated with anti-human IgG antibodies (alkaline phosphatase-labelled) 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;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)

CPT Code Information

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)

84182-CRMWS (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
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
618905 IFA Notes 48767-8

Report Available

10 to 17 days

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.

Clinical Reference

1. McKeon A, Pittock SJ. Overview and diagnostic approach in autoimmune neurology. Continuum (Minneap, Minn). 2024;30(4):960-994. doi:10.1212/CON.0000000000001447

2. Zekeridou A. Paraneoplastic neurologic disorders. Continuum (Minneap, Minn). 2024;30(4):1021-1051. doi:10.1212/CON.0000000000001449

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
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
CRMWS CRMP-5-IgG Western Blot, S Yes 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