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HelpTest Code AN3TS Antineuronal Nuclear Antibody Type 3 (ANNA-3) Titer, Serum
Specimen Required
Only orderable as a reflex. For more information see:
-PAVAL / Paraneoplastic, Autoantibody Evaluation, Serum
-DMS2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Serum
-ENS2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
-EPS2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Serum
-MDS2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Serum
-AIAES / Axonal Neuropathy, Autoimmune/Paraneoplastic Evaluation, Serum
-MAS1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Useful For
Evaluating patients who present with a subacute neurological disorder of undetermined etiology and have risk factors for primary lung carcinoma
Reporting an end titer result from serum specimens
Testing Algorithm
If the indirect immunofluorescence pattern suggests antineuronal nuclear antibody type 3 (ANNA-3), then this test will be performed at an additional charge.
Method Name
Only orderable as a reflex. For more information see:
-PAVAL / Paraneoplastic, Autoantibody Evaluation, Serum
-DMS2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Serum
-ENS2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
-EPS2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Serum
-MDS2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Serum
-AIAES / Axonal Neuropathy, Autoimmune/Paraneoplastic Evaluation, Serum
-MAS1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Serum
Indirect Immunofluorescence Assay (IFA)
Reporting Name
ANNA-3 Titer, SSpecimen Type
SerumSpecimen Minimum Volume
0.6 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
Antineuronal nuclear autoantibodies (ANNA) are recognized clinically as markers of a patient's immune response to specific cancers (paraneoplastic autoantibodies).
In 1985, an antineuronal nuclear autoantibody (now known as ANNA-1 or anti-Hu)(1) was described as a serological accompaniment of subacute sensory neuropathy related to small-cell lung carcinoma (SCLC). ANNA-1 was subsequently recognized as an IgG marker for a spectrum of encephalomyeloradiculoneuropathy (including gastrointestinal dysmotilities) related to SCLC,(2) childhood neuroblastoma, and thymoma. The second antineuronal nuclear antibody to be recognized (known as ANNA-2 or anti-Ri) is an IgG marker of neurological autoimmunity related to SCLC and breast carcinoma.(3)
ANNA-3 is an IgG marker of an immune response to SCLC in patients presenting with a subacute, usually multifocal, paraneoplastic neurologic disorder.(4) Paraneoplastic sensorimotor neuropathy, cerebellar ataxia, and limbic encephalopathy are the most common presentations. However, an ANNA-3-positive patient may present with any element of an encephalomyeloradiculoneuropathy.
Other autoantibody markers of immune responses to SCLC include amphiphysin, collapsin response-mediated protein-5 (CRMP-5) IgG, Purkinje cell antibody type 2 (PCA-2), antiglial neuronal nuclear antibody (AGNA-1), voltage-gated calcium channel (P/Q-type) and potassium channel (VGKC) antibodies and muscle acetylcholine receptor antibodies.
Reference Values
Only orderable as a reflex. For more information see:
-PAVAL / Paraneoplastic, Autoantibody Evaluation, Serum
-DMS2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Serum
-ENS2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum
-EPS2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Serum
-MDS2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Serum
-AIAES / Axonal Neuropathy, Autoimmune/Paraneoplastic Evaluation, Serum
-MAS1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Serum
<1:240
Neuron-restricted patterns of IgG staining that do not fulfill criteria for antineuronal nuclear antibody type 3 may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."
Interpretation
A positive result confirms that a patient's subacute neurological disorder has an autoimmune basis and predicts with 90% certainty that the patient has an aerodigestive carcinoma, usually a small-cell lung carcinoma (SCLC) that is new or recurrent and confined to the chest.
Fifteen percent of patients who are eventually proven to have small-cell carcinoma have an unrelated often more obvious cancer, either coexisting or in the past.
Antineuronal nuclear antibody type 3 (ANNA-3) has not yet been encountered in healthy subjects (n=100) or patients with lung carcinoma without a neurological accompaniment (n=100) or with other cancers (n=300).
Cautions
Antineuronal nuclear antibody type 3 (ANNA-3) is not detectable when it coexists with ANNA-1 or ANNA-2 unless its titer exceeds that of coexisting neuronal nuclear antibodies or is demonstrable by Western blot.
Clinical Reference
1. Graus F, Cordon-Cardo C, Posner JB: Neuronal antinuclear antibody in sensory neuropathy from lung cancer. Neurology. 1985 Apr;35(4):538-543
2. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncologic profile of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998 Mar;50(3):652-657
3. Vernino S, Eggenberger ER, Rogers LR, Lennon VA: Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma. Neurology. 2002 Sep 24;59(6):929-932
4. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody-type 2: paraneoplastic accompaniments. Ann Neurol. 2003 May;53(5):580-587
5. Chan KH, Vernino S, Lennon VA: ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol 2001 September;50(3):301-311
6. Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov;56(5):715-719
7. 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
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)
Western blot is performed, as needed, to confirm seropositivity.
Day(s) Performed
Monday through Sunday
Report Available
5 to 8 daysSpecimen Retention Time
28 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 |
|---|---|---|
| AN3TS | ANNA-3 Titer, S | 94344-9 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 43433 | ANNA-3 Titer, S | 94344-9 |