Test Catalog

Test Id : DYS2

Dysautonomia, Autoimmune/Paraneoplastic Evaluation, Serum

Useful For
Suggests clinical disorders or settings where the test may be helpful

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
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

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
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial 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
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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
A short description of the method used to perform the test

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

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Dysautonomia, Autoimm/Paraneo, S

Aliases
Lists additional common names for a test, as an aid in searching

ANNA (Antineuronal Nuclear Antibody)

Anti-CV2

Anti-Enteric Neuronal Antibody

Anti-Hu

Antineuronal

Cerebellar Antibodies

Chorea

Collapsin Response-Mediator Protein-5 Antibody (CRMP-5), Serum

Cramp-fasciculation

CRMP-5, IgG

Dorsal Root Ganglion Antibody

DPPX

Hu Antibody

Isaacs disease

Motor End-Plate Antibody

Motor Nerve Terminal Antibodies

Myoid Antibody

Neuromuscular hyperexcitability

Neuromyotonia

Neuronal ganglionic acetylcholine receptor antibody

Neuronal Nuclear Antibody Panel

Neuronal-Anti

Paraneoplastic Antibodies

Paraneoplastic Autoantibody Evaluation

Paraneoplastic Neurological Autoimmunity

Dipeptidyl aminopeptidase-like protein 6

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Specimen Type
Describes the specimen type validated for testing

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
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

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.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the testing laboratory. The minimum volume is sufficient for one attempt at testing.

2.5 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

Useful For
Suggests clinical disorders or settings where the test may be helpful

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)

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

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.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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
Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Test ID

Reporting name

Methodology*

Reference value

ADEI

Dysautonomia, Interpretation, S

Medical interpretation

Interpretive report

GANG

AChR Ganglionic Neuronal Ab, S

RIA

< or =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
Provides information to assist in interpretation of the test results

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
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Negative results do not exclude autoimmune dysautonomia or cancer.

 

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

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Cutsforth-Gregory JK, McKeon A, Coon EA, et al. Ganglionic antibody level as a predictor of severity of autonomic failure. Mayo Clin Proc. 2018;93(10):1440-1447. doi:10.1016/j.mayocp.2018.05.033

2. Tobin WO, Lennon VA, Komorowski L, et al. DPPX potassium channel antibody: frequency, clinical accompaniments, and outcomes in 20 patients. Neurology. 2014;83(20):1797-1803. doi:10.1212/WNL.0000000000000991

Method Description
Describes how the test is performed and provides a method-specific reference

Cell Binding Assay:

Patient specimen 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)

 

Indirect Immunofluorescence Assay:

The patient's sample is tested by a standardized immunofluorescence assay that uses a composite frozen section of mouse cerebellum, kidney, and gut tissues. After incubation with sample 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)

 

Radioimmunoassay:

(125)I-labeled recombinant human antigens or labeled receptors are incubated with patient specimen. 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 specimen. Results are reported as units of precipitated antigen (nmol) per liter of patient sample.(Griesmann GE, Kryzer TJ, Lennon VA. Autoantibody profiles of myasthenia gravis and Lambert-Eaton myasthenic syndrome. In: Rose NR, Hamilton RG, eds. Manual of Clinical and Laboratory Immunology. 6th ed. ASM Press; 2002:1005-1012; Walikonis JE, Lennon V.A Radioimmunoassay for glutamic acid decarboxylase [GAD65] autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc. 1998 December;73[12]:1161-1166; 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)

 

Immunoblot:

All steps are performed at room temperature (18 to 28 degrees 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 samples will bind to the purified recombinant antigen and negative samples will not bind. Strips are washed to remove unbound serum 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-indolylphosphate substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produces 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, Kim K, Benarroch EE, Lennon VA. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 February;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)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

8 to 12 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

28 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees :
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their account representative. For assistance, contact Customer Service.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

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® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
DYS2 Dysautonomia, Autoimm/Paraneo, S 99000-2
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
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
618892 IFA Notes 48767-8
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

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports

Test Update Resources

Change Type Effective Date
File Definition - Algorithm 2024-06-04