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HelpTest Code AN2TC Antineuronal Nuclear Antibody Type 2 (ANNA-2) Titer, Spinal Fluid (Non-Orderable)
Ordering Guidance
Both serum and spinal fluid testing are suggested. Spinal fluid testing is particularly useful when interfering antibodies are present in the serum.
Specimen Required
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
Useful For
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
Serological evaluation of patients who present with a subacute neurological disorder and 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 use or passive exposure
Directing a focused search for cancer
Investigating neurological symptoms that appear during, or after, cancer therapy, and are not explainable by metastasis
Reporting an end titer result from cerebrospinal fluid specimens
Testing Algorithm
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
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)
Reporting Name
ANNA-2 Titer, CSFSpecimen Type
CSFSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| CSF | Refrigerated (preferred) | 28 days |
| Frozen | 28 days | |
| Ambient | 72 hours |
Reject Due To
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
Clinical Information
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 a paraneoplastic neurological syndrome. 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. 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]); coexisting paraneoplastic autoantibodies are found in 73% of cases.
Antineuronal nuclear autoantibody type 2 positive patients are female in 64% of cases. Most have primary carcinoma of breast or lung; gynecologic cancer is less frequent.
Antineuronal nuclear autoantibody type 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.
Antineuronal nuclear autoantibody type 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 confirmed by a line blot assay.
Reference Values
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
Interpretation
Detection of antineuronal nuclear autoantibodies type 2 (ANNA-2) in serum or spinal fluid of patients with a compatible neurologic disorder:
-Identifies the neurologic problem as autoimmune and almost certainly paraneoplastic
-Prompts a search for underlying malignancy (breast, lung, or gynecologic)
Antineuronal nuclear autoantibody type 2 is specific for the nova1/nova2 proteins.
Cautions
Presence of non-neural specific antibodies in a patient’s specimen may hinder interpretation of antineuronal nuclear autoantibody type 2 (ANNA-2) results by tissue indirect immunofluorescence.
Clinical Reference
1. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody-type 2: paraneoplastic accompaniments. Ann Neurol. 2003;53(5):580-587
2. Horta ES, Lennon VA, Lachance DH, et al: Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014;20(14):3862-3869
3. Zekeridou A. Paraneoplastic neurologic disorders. Continuum (Minneap Minn). 2024;30(4):1021-1051. doi:10.1212/CON.0000000000001449
Method Description
The patient's specimen is tested by a standardized immunofluorescence assay that uses a composite frozen section of mouse cerebrum, cerebellum, kidney, and gut tissues. After incubation with the specimen and washing, fluorescein-conjugated goat-antihuman IgG is applied. Neuron-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Specimens that are scored positive for any neuronal nuclear or cytoplasmic autoantibody are titrated. Interference by coexisting non-neuron-specific autoantibodies can usually be eliminated by serologic absorption.(Unpublished Mayo method)
If antineuronal nuclear autoantibody type 1 (ANNA-1), antinuclear antibody, or antimitochondrial antibody titers equal or exceed ANNA-2, Western blot analysis may be required to establish ANNA-2 specificity with certainty.
Day(s) Performed
Monday through Sunday
Report Available
5 to 8 daysSpecimen Retention Time
2 daysPerforming 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
86256
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| AN2TC | ANNA-2 Titer, CSF | 94357-1 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 43441 | ANNA-2 Titer, CSF | 94357-1 |