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Test Code PAVAL Paraneoplastic, Autoantibody Evaluation, Serum

Reporting Name

Paraneoplastic Autoantibody Eval, S

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
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
NMOFS NMO/AQP4 FACS, S Yes No
NMOTS NMO/AQP4 FACS Titer, S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No
LG1CS LGI1-IgG CBA, S No No
CS2CS CASPR2-IgG CBA, S No 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 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 FACS is performed at an additional charge.

 

If NMO/AQP4-IgG FACS screen assay requires further evaluation, then NMO/AQP4-IgG FACS titration assay 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.

 

If VGKC >0.00, LGI1-IgG CBA, S and CASPR2-IgG CBA, S are performed at an additional charge.

 

See Paraneoplastic Evaluation Algorithm in Special Instructions

Performing Laboratory

Mayo Medical Laboratories in Rochester

Specimen Type

Serum


Necessary Information


Include relevant clinical information, name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.



Specimen Required


Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 4 mL


Specimen Minimum Volume

2 mL

Specimen Stability Information

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

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.

 

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."

 

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

  

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 FACS 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

Leucine-Rich Glioma Inactivated Protein-1 IgG (LGI1) CBA

Negative

Contactin-Associated Protein-Like-2 IgG (CASPR2) CBA

Negative

Day(s) and Time(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 Friday; 11:30 a.m. and 8 p.m.; Saturday and Sunday; 8 a.m.

Striational (striated muscle) antibodies: Monday through Friday; 4 a.m. and 3 p.m.; Saturday; 6 a.m.

P/Q-type calcium channel antibody, N-type calcium channel antibody, AChR ganglionic neuronal antibody, neuronal (V-G) K+ channel autoantibody: Monday through Friday; 11 a.m. and 6 p.m.; Saturday and Sunday; 6 a.m.

ACh receptor (muscle) binding antibody: Monday through Friday;11 a.m., 6 p.m., and 10 p.m.; Saturday; 6 a.m.; Sunday; 6 a.m. and 10 a.m.

Paraneoplastic autoantibody Western blot, CRMP-5-IgG Western blot, Amphiphysin Western blot: Monday, Wednesday, Friday; 8 a.m.

GAD65 antibody assay: Monday through Friday; 6 a.m. and 4 p.m.

ACh receptor (muscle) modulating antibodies: Monday through Thursday; 2 p.m., Saturday; 8 a.m.

NMO/AQP4 IgG FACS; Monday, Tuesday, Thursday; 6:00 p.m.

NMDCS, AMPCS, GABCS, LGICS, CS2CS: Monday through Friday; 6 a.m.

Test Classification

See Individual Test IDs

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 FACS (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)

86256-NMO/AQP4-IgG FACS titer (if appropriate)

86341-GAD65 antibody assay (if appropriate)

86255-LG1CS (if appropriate)

86255-CS2CS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PAVAL Paraneoplastic Autoantibody Eval, S In Process

 

Result ID Test Result Name Result LOINC Value
80776 ANNA-2, S 43188-2
83137 ANNA-3, S 33924-2
8338 ACh Receptor (Muscle) Binding Ab 11034-6
81184 N-Type Calcium Channel Ab 33979-6
81185 P/Q-Type Calcium Channel Ab 33980-4
83077 CRMP-5-IgG, S 35386-2
84321 AChR Ganglionic Neuronal Ab, S 42233-7
29347 Interpretive Comments 69048-7
83138 PCA-2, S 33925-9
9477 PCA-1, S 53717-5
83076 PCA-Tr, S 33926-7
8746 Striational (Striated Muscle) Ab, S 8097-8
89165 Neuronal (V-G) K+ Channel Ab, S 41871-5
89080 AGNA-1, S 53709-2
81722 Amphiphysin Ab, S 33927-5
80150 ANNA-1, S 13997-2
36349 Reflex Added No LOINC Needed

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.

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.

Clinical Reference

1. Lennon VA: Calcium channel and related paraneoplastic disease autoantibodies. In Textbook of Autoantibodies. Edited by JB Peter, Y Schoenfeld. The Netherlands, Elsevier Science Publishers, B.V., 1996, pp 139-147

2. Voltz R, Gultekin SH, Rosenfeld MR, et al: A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med 1999 June 10;340(23):1788-1795

3. Vernino S, Tuite P, Adler CH, et al: Paraneoplastic chorea associated with CRMP-5 neuronal antibody and lung carcinoma. Ann Neurol 2002 May;51(1):625-630

4. Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol 2004;56(5):715-719

5. Sabater L, Saiz A, Titulaer MG, et al: Sox 1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology 2007;68(Suppl 1):A290-A291

6. Dalmau J, Tuzun E, Wu H-Y, et al: Paraneoplastic anti-N-methyl-D-asparate receptor encephalitis associated with ovarian teratome. Ann Neurol 2007;61:25-36

7. Tan K. Lennon V, Pittock S: Voltage-gated potassium channel (VGKC) autoimmunity, Abstract, Annual Meeting of American Neurological Association, Washington DC, (October) 2007

8. Pittock SJ, Lucchinetti DF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005:58(1):96-107

Analytic Time

10 days (Negative)

Reject Due To

Hemolysis

Mild OK; Gross reject

Lipemia

Mild OK; Gross reject

Icterus

Mild OK; Gross reject

Other

NA

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, ABLOT: Western Blot

NMDCS, AMPCS, GABCS, LG1CS, CS2CS: Cell-Binding Assay (CBA)

NMOTS: Flow Cytometry

Forms

If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

General Request Form (T239) (http://www.mayomedicallaboratories.com/it-mmfiles/general-request-form.pdf))

Neurology Specialty Testing Client Test Request (T732) (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)