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Order Code LAB2889 Paraneoplastic, Autoantibody Evaluation, Serum

Important Note

INCLUDES REFLEX TO :

 

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

 

Additional Codes

Mayo Test ID
PAVAL


EPIC Test Code: LAB2889
 

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 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 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.


Ridgeview Laboratory Note:

When ordering #83107 “CRMP-5-IgG Western Blot,” use RMC #40192; for #83379 “ACh Receptor (Muscle) Blocking Ab”, use RMC #40463; and for #83378 “ACh Receptor (Muscle) Modulating Ab”, use RMC #40042.

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

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

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.

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

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)

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)

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

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:

-Paraneoplastic Evaluation Algorithm-Serum

-Hereditary Peripheral Neuropathy Diagnostic Algorithm

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)