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Test Code DYS2 Dysautonomia, Autoimmune/Paraneoplastic Evaluation, Serum


Ordering Guidance


Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, refer to Autoimmune Neurology Test Ordering Guide.

 

When more than one evaluation is ordered on the same order number, the duplicate test will be canceled.

 

For a list of antibodies performed with each evaluation, see Autoimmune Neurology Antibody Matrix.

 

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 before 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.


Useful For

Investigating idiopathic dysautonomic symptoms

 

Directing a focused search for cancer in patients with idiopathic dysautonomia

 

Investigating autonomic symptoms that appear in the course or wake of cancer therapy and are not explainable by recurrent cancer or metastasis (detection of autoantibodies in this profile helps differentiate autoimmune dysautonomia from the effects of chemotherapy)

Profile Information

Test ID Reporting Name Available Separately Always Performed
ADEI Dysautonomia, Interpretation, S No Yes
GANG AChR Ganglionic Neuronal Ab, S No Yes
ANN1S Anti-Neuronal Nuclear Ab, Type 1 No Yes
APBIS AP3B2 IFA, S No Yes
CRMS CRMP-5-IgG, S No Yes
CS2CS CASPR2-IgG CBA, S No Yes
DPPCS DPPX Ab CBA, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AN1BS ANNA-1 Immunoblot, S No No
AN2BS ANNA-2 Immunoblot, S No No
DPPTS DPPX Ab IFA Titer, S No No
AN1TS ANNA-1 Titer, S No No
APBCS AP3B2 CBA, S No No
APBTS AP3B2 IFA Titer, S No No
CRMTS CRMP-5-IgG Titer, S No No
PC2TS PCA-2 Titer, S No No
CRMWS CRMP-5-IgG Western Blot, S Yes No

Testing Algorithm

If the indirect immunofluorescence assay (IFA) patterns suggest collapsin response-mediator protein (CRMP)-5-IgG, then the CRMP-5-IgG IFA titer and CRMP-5-IgG Western blot will be performed at an additional charge.

 

If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 immunoblot, ANNA-1 IFA titer, and ANNA-2 immunoblot will be performed at an additional charge.

 

If the IFA pattern suggests adaptor protein 3 beta 2 (AP3B2) antibody, then the AP3B2 cell-binding assay (CBA) and AP3B2 IFA titer will be performed at an additional charge.

 

If the dipeptidyl-peptidase-like protein-6 antibody (DPPX) antibody CBA result is positive, then DPPX IFA titer will be performed at an additional charge.

 

If the IFA pattern suggests Purkinje cytoplasmic antibody type 2 (PCA-2), then the PCA-2 titer is performed at an additional charge.

 

For more information see Autoimmune/Paraneoplastic Dysautonomia Evaluation Algorithm.

Method Name

ANN1S, AN1TS, APBIS, APBTS, DPPTS, PCAB2, PC2TS, CRMS, CRMTS: Indirect Immunofluorescence Assay (IFA)

 

APBCS, CS2CS, DPPCS, LG1CS: Cell Binding Assay (CBA)

 

CRMWS: Western Blot (WB)

 

AN1BS, AN2BS: Immunoblot (IB)

 

GANG: Radioimmunoassay (RIA)

 

ADEI: Medical Interpretation

Reporting Name

Dysautonomia, Autoimm/Paraneo, S

Specimen Type

Serum

Specimen Minimum Volume

2.5 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

Clinical Information

Autoimmune dysautonomia encompasses disorders of peripheral autonomic synapses, ganglionic neurons, autonomic nerve fibers, and central autonomic pathways mediated by neural-specific IgG or effector T cells. These disorders may be idiopathic or paraneoplastic, subacute or insidious in onset, and may present as a limited disorder or generalized pandysautonomia. Pandysautonomia is usually subacute in onset and severity and includes impaired pupillary light reflex, anhidrosis, orthostatic hypotension, cardiac arrhythmias, gastrointestinal dysmotility, sicca manifestations, and bladder dysfunction. Limited dysautonomia is confined to one or just a few domains, is often mild, and may include sicca manifestations, postural orthostatism and cardiac arrhythmias, bladder dysfunction, or gastrointestinal dysmotilities. Diagnosis of limited dysautonomia requires documentation of objective abnormalities by autonomic reflex testing, thermoregulatory sweat test, or gastrointestinal motility studies.

 

The most frequently encountered autoantibody marker of autoimmune dysautonomia is the neuronal ganglionic alpha-3-acetylcholine receptor (AChR) autoantibody. This autoantibody to date is the only proven effector of autoimmune dysautonomia. A direct relationship has been demonstrated between antibody titer and severity of dysautonomia in both alpha-3-AChR-immunized animals and patients with autoimmune dysautonomia. Patients with high alpha-3-AChR autoantibody values (>1.0 nmol/L) generally have profound pandysautonomia. Dysautonomic patients with lower alpha-3-AChR autoantibody values (0.03-0.99 nmol/L) have limited dysautonomia.

 

Importantly, cancer is detected in 30% of patients with alpha-3-AChR autoantibody. Cancers recognized include small-cell lung carcinomas, thymoma, lymphoma, and adenocarcinomas of breast, lung, prostate, and gastrointestinal tract. Cancer risk factors include a previous or family history of cancer, history of smoking, or social or environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favors neurologic improvement and lessens morbidity.

 

Autoantibodies to other onconeural proteins shared by neurons, glia, or muscle (eg, antineuronal nuclear antibody-type 1 [ANNA-1], collapsin response-mediator protein-5 neuronal [CRMP-5-IgG]) serve as additional markers of paraneoplastic or idiopathic dysautonomia. A specific neoplasm is often predictable by the individual patient's autoantibody profile.

Reference Values

Test ID

Reporting name

Methodology*

Reference value

ADEI

Dysautonomia, Interpretation, S

Medical interpretation

Interpretive report

GANG

AChR Ganglionic Neuronal Ab, S

RIA

≤0.02 nmol/L

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

Negative

APBIS

AP3B2 IFA, S

IFA

Negative

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMS

CRMP-5-IgG, S

IFA

Negative

DPPCS

DPPX Ab CBA, S

CBA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

Negative

 

Reflex Information:

Test ID

Reporting name

Methodology*

Reference value

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN1TS

ANNA-1 Titer, S

IFA

<1:240

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

APBCS

AP3B2 CBA, S

CBA

Negative

APBTS

AP3B2 IFA Titer, S

IFA

<1:240

CRMTS

CRMP-5-IgG Titer, S

IFA

<1:240

CRMWS

CRMP-5-IgG Western Blot, S

WB

Negative

DPPTS

DPPX Ab IFA Titer, S

IFA

<1:240

PC2TS

PCA-2 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 ANNA-1, CRMP-5-IgG, or PCA-2 may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal 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.

Interpretation

Antibodies directed at onconeural proteins shared by neurons, muscle, and glia are valuable serological markers of a patient's immune response to cancer. These autoantibodies are not found in healthy subjects and are usually accompanied by subacute neurological signs and symptoms. It is not uncommon for more than one autoantibody to be detected in patients with autoimmune dysautonomia. These include:

-Plasma membrane cation channel antibodies (neuronal ganglionic [alpha-3]). These autoantibodies are potential effectors of autonomic dysfunction.

-Antineuronal nuclear antibody-type 1 (ANNA-1)

-Neuronal and muscle cytoplasmic antibodies (collapsin response-mediator protein-5 neuronal [CRMP-5 IgG])

 

A rising autoantibody titer in previously seropositive patients suggests cancer recurrence.

Cautions

Negative results do not exclude autoimmune dysautonomia or cancer.

 

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

Report Available

8 to 12 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

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

86255 x 7

84182 AN1BS (if appropriate)

86256 AN1TS (if appropriate)

84182 AN2BS (if appropriate)

86255 APBCS (if appropriate)

86256 APBTS (if appropriate)

86256 CRMTS (if appropriate)

84182 CRMWS (if appropriate)

86256 DPPTS (if appropriate)

86256 PC2TS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DYS2 Dysautonomia, Autoimm/Paraneo, S 99000-2

 

Result ID Test Result Name Result LOINC Value
80150 ANNA-1, S 33615-6
83077 CRMP-5-IgG, S 72504-4
84321 AChR Ganglionic Neuronal Ab, S 94694-7
83138 PCA-2, S 84925-7
34270 Dysautonomia, Interpretation, S 69048-7
64279 LGI1-IgG CBA, S 94287-0
64281 CASPR2-IgG CBA, S 94285-4
64933 DPPX Ab CBA, S 94676-4
615863 AP3B2 IFA, S 101907-4
618892 IFA Notes 48767-8