Test Catalog

Test Id : AN2TC

Not Orderable

Antineuronal Nuclear Antibody Type 2 (ANNA-2) Titer, Spinal Fluid

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Overview

Test Catalog

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

Investigating middle-aged or older patients who present with unexplainable signs of midbrain/cerebellar/brain stem disorder and/or myelopathy, especially women with a previous history of breast cancer, and both sexes if there is a history of tobacco abuse or passive exposure

 

Reporting an end titer result from cerebrospinal fluid specimens

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

If the indirect immunofluorescence pattern suggests antineuronal nuclear antibody type 2 (ANNA-2), then this test will be performed at an additional charge.

Method Name
A short description of the method used to perform the test

Only orderable as a reflex. For more information see:

-DMC2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-ENC2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-EPC2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MDC2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MAC1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

 

Indirect Immunofluorescence Assay (IFA)

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

ANNA-2 Titer, CSF

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

ANNA-2 (Antineuronal Nuclear Antibody Type 2)

Anti-Ri

Antineuronal Nuclear Antibody Type 2

Ri Antibody

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

If the indirect immunofluorescence pattern suggests antineuronal nuclear antibody type 2 (ANNA-2), then this test will be performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

CSF

Ordering Guidance

For investigating a smoker presenting with 1 or more elements of encephalomyeloradiculoneuropathy, order PAVAL / Paraneoplastic Autoantibody Evaluation, Serum.

 

Serum is preferred. Spinal fluid testing is particularly useful when interfering antibodies are present in the serum.

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

Only orderable as a reflex. For more information see:

-DMC2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-ENC2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-EPC2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MDC2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MAC1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

 

Container/Tube: Sterile vial

Specimen Volume: 2 mL

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

1 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
CSF Refrigerated (preferred) 28 days
Frozen 28 days
Ambient 72 hours

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

Investigating middle-aged or older patients who present with unexplainable signs of midbrain/cerebellar/brain stem disorder and/or myelopathy, especially women with a previous history of breast cancer, and both sexes if there is a history of tobacco abuse or passive exposure

 

Reporting an end titer result from cerebrospinal fluid specimens

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

If the indirect immunofluorescence pattern suggests antineuronal nuclear antibody type 2 (ANNA-2), then this test will be performed at an additional charge.

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

Antineuronal nuclear autoantibody type 2 (ANNA-2), also known as anti-Ri, is an IgG serologic marker of paraneoplastic neurologic autoimmunity and reflects an immune response to neuronal antigens expressed in certain breast, lung, or gynecologic cancers. These carcinomas are often occult, with the patients presenting with unexplained signs of neurologic dysfunction. ANNA-2 is far less common than ANNA-1. It is one of the rarest paraneoplastic antibodies encountered in the Mayo Clinic Neuroimmunology Laboratory.

 

Patients who are seropositive for ANNA-2 usually present to a neurologist with signs of midbrain, brain stem, cerebellar, or spinal cord dysfunction. Some have sensorimotor neuropathy. Ocular opsoclonus-myoclonus, laryngospasm, or jaw-opening dystonia may be prominent. Peripheral neuropathic signs and symptoms may occur. These often reflect coexisting autoimmunity to other onconeural proteins (eg, ANNA-1, collapsin response-mediator protein-5 [CRMP-5], calcium channels); coexisting paraneoplastic autoantibodies are found in 73% of cases.

 

ANNA-2 positive patients are female in 64% of cases. Most have a primary carcinoma of breast or lung; gynecologic cancer is less frequent.

 

Treatment of the cancer can lead to progressive reduction in ANNA-2 titer and stabilization or striking improvement of the neurologic disorder.

 

ANNA-2 is not detected in serum or spinal fluid of healthy individuals. It is found in fewer than 2% of patients who have small-cell lung carcinoma without evidence of neurologic dysfunction.

 

ANNA-2 is identified by an indirect immunofluorescence assay. It characteristically stains neurons in the central nervous system and spares neurons in the peripheral nervous system. ANNA-2 is also identifiable by neuronal Western blot characteristics.

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.

Only orderable as a reflex. For more information see:

-DMC2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-ENC2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-EPC2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MDC2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

-MAC1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Spinal Fluid

 

<1:2

Neuron-restricted patterns of IgG staining that do not fulfill criteria for antineuronal nuclear antibody type 2 may be reported as "unclassified antineuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

Interpretation
Provides information to assist in interpretation of the test results

Detection of antineuronal nuclear autoantibodies type 2 (ANNA-2) in serum or spinal fluid of patients with a clinically unexplainable neurologic disorder:

-Identifies the neurologic problem as autoimmune and almost certainly paraneoplastic

-Prompts a search for underlying malignancy (breast, lung, or gynecologic)

-Leads to early treatment of cancer and consideration of immunosuppressant therapy

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

Seronegativity for antineuronal nuclear antibody type 2 (ANNA-2) does not exclude malignancy.

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

1. Kiers L, Altermatt HJ, Lennon VA: Paraneoplastic anti-neuronal nuclear IgG autoantibodies (type 1) localize antigen in small cell lung carcinoma. Mayo Clin Proc. 1991 Dec;66(12):1209-1216

2. Lennon VA: Paraneoplastic autoantibodies: the case for a descriptive generic nomenclature. Neurology. 1994 Dec;44(12):2236-2240

3. Lennon VA, Kryzer TJ, Griesmann GE, et al: Calcium-channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes. N Engl J Med. 1995 Jun 1;332(22):1467-1474

4. Chan KH, Vernino S, Lennon VA: ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol. 2001 Sep;50(3):301-311

5. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody-type 2: paraneoplastic accompaniments. Ann Neurol. 2003 May;53(5):580-587

6. Horta ES, Lennon VA, Lachance DH, et al: Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014 Jul 15;20(14):3862-3869

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

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 Jul 18;4(5):e385. doi: 10.1212/NXI.0000000000000385)

 

If antineuronal nuclear autoantibody type 1 (ANNA-1), antinuclear antibody, or antimitochondrial antibody titers equal or exceed ANNA-2, Western blot analysis is required to establish ANNA-2 specificity with certainty.

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.

Monday through Sunday

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.

5 to 8 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.

86256

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
AN2TC ANNA-2 Titer, CSF 94357-1
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.
43441 ANNA-2 Titer, CSF 94357-1

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 | PHP Pdf | CMS 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