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Test Code 9410 Paraneoplastic, Autoantibody Evaluation, Serum

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Serum


Necessary Information


Provide the following information:

-Relevant clinical information

-Ordering Provider name, phone number, mailing address, and e-mail address



Specimen Required


Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication.

2. 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 1 week and assayed if sufficiently decayed, or canceled if radioactivity remains.

3. Patient should have no general anesthetic or muscle-relaxant drugs in the previous 24 hours.

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

Test ID

Reporting Name

Methodology

Reference Value

GANG

AChR Ganglionic Neuronal Ab, S

Radioimmunoassay (RIA)

≤0.02 nmol/L

AMPHS

Amphiphysin Ab, S

Immunofluorescence (IFA)

<1:240

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

<1:240

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

<1:240

ANN2S

Anti-Neuronal Nuclear Ab, Type 2

IFA

<1:240

ANN3S

Anti-Neuronal Nuclear Ab, Type 3

IFA

<1:240

CRMS

CRMP-5-IgG, S

IFA

<1:240

VGKC

Neuronal (V-G) K+ Channel Ab, S

RIA

≤0.02 nmol/L

CCN

N-Type Calcium Channel Ab

RIA

≤0.03 nmol/L

CCPQ

P/Q-Type Calcium Channel Ab

RIA

≤0.02 nmol/L

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

<1:240

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

<1:240

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

<1:240

STR

Striational (Striated Muscle) Ab, S

Enzyme-linked immunosorbent assay (ELISA)

<1:120

 

Reflex Tests:

Test ID

Reporting Name

Methodology

Reference Value

ARBI

ACh Receptor (Muscle) Binding Ab

RIA

≤0.02 nmol/L

ARMO

ACh Receptor (Muscle) Modulating Ab

Live-cell assay (LCA)

0-20%

AMPCS

AMPA-R Ab CBA, S

Cell-binding assay (CBA)

Negative

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

ABLOT

Amphiphysin Western Blot, S

Western blot (WB)

Negative

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMWS

CRMP-5-IgG Western Blot, S

WB

Negative

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPIS

DPPX Ab IFA, S

IFA

Negative

DPPTS

DPPX Ab IFA Titer, S

IFA

<1:240

GABCS

GABA-B-R Ab CBA, S

CBA

Negative

GABIS

GABA-B-R Ab IF Titer Assay, S

IFA

<1:120

GD65S

GAD65 Ab Assay, S

RIA

≤0.02 nmol/L

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

GL1TS

mGluR1 Ab IFA Titer, S

IFA

<1:240

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

NMDIS

NMDA-R Ab IF Titer Assay, S

IFA

<1:120

WBN

Paraneoplastic Autoantibody WBlot,S

WB

Negative

 

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: 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 to request CRMP-5 Western blot.

Day(s) and Time(s) Performed

ANN1S, ANN2S, ANN3S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AGN1S, DPPTS, DPPIS, GL1IS, GL1TS, AMPIS, GABIS, NMDIS:

Monday through Friday; 5 a.m., 7 a.m., 5 p.m.

Saturday, Sunday; 6 a.m.

 

STR:

Monday through Friday; 4 a.m., 3 p.m.

Saturday, Sunday; 6 a.m.

 

ARBI, CCN, CCPQ, GANG, VGKC:

Monday through Friday; 6 a.m., 8 a.m., 6 p.m.

Saturday, Sunday; 7 a.m.

 

ABLOT, CRMWS, WBN:

Monday through Thursday; 8 a.m.

 

GD65S:

Monday through Friday; 5 a.m. and 2 p.m.

Saturday, Sunday; 7 a.m.

           

ARMO:

Monday through Thursday; 2 p.m.

Saturday; 8 a.m.

 

AMPCS, CS2CS, GABCS, LG1CS, NMDCS:

Monday through Thursday; 10 p.m.       

Sunday; 3 p.m.

 

DPPCS, GL1CS:

Wednesday; 6 p.m.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

83519x4

86255x9

83520

 

83519-ACh receptor (muscle) binding antibody (if appropriate)

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-AMPCS (if appropriate)

86255-GABCS (if appropriate)

86255-NMDCS (if appropriate)

86256-AMPIS (if appropriate)

86256-GABIS (if appropriate)

86256-NMDIS (if appropriate)

86341-GAD65 antibody assay (if appropriate)

86255-LG1CS (if appropriate)

86255-CS2CS (if appropriate)

86255-DPPCS (if appropriate)

86255-DPPIS (if appropriate)

86256-DPPTS (if appropriate)

86255-GL1CS (if appropriate)

86255-GL1IS (if appropriate)

86256-GL1TS (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
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 56550-7
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 77202-0

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. McKeon A, Pittock SJ: Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol 2011;122:381-400

2. Horta ES, Lennon VA, Lachance DH, et al: Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res 2014;20:3862-3869

Method Name

ANN1S, ANN2S, ANN3S, PCABP, PCAB2, PCATR, AMPHS, CRMS, AGN1S, AMPIS, NMDIS, GABIS, DPPIS, DPPTS, GL1IS, GL1TS: Indirect Immunofluorescence Assay (IFA)

STR: Enzyme-Linked Immunosorbent Assay (ELISA)

CCPQ, CCN, ARBI, GANG, VGKC, GD65S: Radioimmunoassay (RIA)

WBN, ABLOT, CRMWS: Western Blot

NMDCS, AMPCS, GABCS, LG1CS, CS2CS, DPPCS, GL1CS: Cell-Binding Assay (CBA)

ARMO: Live Cell Assay (LCA)

Profile Information

Test ID Reporting Name Available Separately Always Performed
PAINT Interpretive Comments No Yes
GANG AChR Ganglionic Neuronal Ab, S 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
CCN N-Type Calcium Channel Ab 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
STR Striational (Striated Muscle) Ab, S Yes Yes

Testing Algorithm

If immunofluorescence assay (IFA) (ANN1S, ANN2S, PCABP, PCAB2) patterns are indeterminate, then paraneoplastic autoantibody Western blot is performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin Western blot is performed at an additional charge.

 

If IFA patterns suggest GAD65 antibody, then GAD65 antibody radioimmunoassay is performed at an additional charge.

 

If IFA pattern suggest NMDA-R, then NMDA-R antibody cell-binding assay (CBA), and/or NMDA-R antibody titer is performed at an additional charge.

 

If IFA pattern suggest AMPA-R, then AMPA-R antibody CBA and/or AMPA-R antibody titer is performed at an additional charge.

 

If IFA pattern suggest GABA-B-R, then GABA-B-R antibody CBA and/or GABA-B-R antibody titer is performed at an additional charge. 

 

If IFA pattern suggest DPPX, then DPPX antibody CBA and DPPX antibody titer is performed at an additional charge.

 

If IFA pattern suggest mGluR1, then mGluR1 antibody CBA and mGluR1 antibody titer is performed at an additional charge.

 

If VGKC is >0.00 nmol/L, then LGI1-IgG CBA and CASPR2-IgG CBA, S are performed at an additional charge.

 

If CRMP IFA is positive, then ACh receptor binding antibody, CRMP-5-IgG Western blot, and ACh receptor (muscle) modulating antibody will be performed at an additional charge.

 

If striational striated muscle antibody is 1:7,680 or greater, then ACh receptor binding antibody, CRMP-5-IgG Western blot, and ACh receptor (muscle) modulating antibody 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 in Special Instructions

-Paraneoplastic Evaluation Algorithm

-Hereditary Peripheral Neuropathy Diagnostic Algorithm

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
ARBI ACh Receptor (Muscle) Binding Ab Yes No
ARMO ACh Receptor (Muscle) Modulating Ab No No
AMPCS AMPA-R Ab CBA, S No No
AMPIS AMPA-R Ab IF Titer Assay, S No No
ABLOT Amphiphysin Western Blot, S No No
CS2CS CASPR2-IgG CBA, S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No
DPPCS DPPX Ab CBA, S No No
DPPIS DPPX Ab IFA, S No No
DPPTS DPPX Ab IFA Titer, S No No
GABCS GABA-B-R Ab CBA, S No No
GABIS GABA-B-R Ab IF Titer Assay, S No No
GD65S GAD65 Ab Assay, S Yes No
LG1CS LGI1-IgG CBA, S No No
GL1CS mGluR1 Ab CBA, S No No
GL1IS mGluR1 Ab IFA, S No No
GL1TS mGluR1 Ab IFA Titer, S No No
NMDCS NMDA-R Ab CBA, S No No
NMDIS NMDA-R Ab IF Titer Assay, S No No
WBN Paraneoplastic Autoantibody WBlot,S No No

Forms

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

-General Request (T239)

-Neurology Specialty Testing Client Test Request (T732)