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HelpTest Code AN1TC Antineuronal Nuclear Antibody-Type 1 (ANNA-1) Titer, Spinal Fluid (Non-Orderable)
Ordering Guidance
Both serum and spinal fluid testing are suggested. Spinal fluid testing is particularly useful if interfering antibodies are present in the serum.
Necessary Information
Provide the ordering physician's name, phone number, mailing address, and e-mail address.
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
PCDEC / Pediatric Autoimmune Encephalopathy/CNS Disorder 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
PCDEC / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Spinal Fluid
Serological evaluation of patients who present with a subacute neurological disorder of undetermined etiology, especially those with risk factors for primary lung carcinoma
Directing a focused search for cancer
Investigating neurological symptoms that appear during, or after, cancer therapy, and are not explainable my metastasis
Reporting an end titer result from cerebrospinal fluid specimens
Testing Algorithm
If the indirect immunofluorescence pattern suggests antineuronal nuclear antibody-type 1 (ANNA-1), 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
PCDEC / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Spinal Fluid
Indirect Immunofluorescence Assay (IFA)
Reporting Name
ANNA-1 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
A spectrum of paraneoplastic neurologic disorders is associated with antineuronal nuclear antibody type1 (ANNA-1), also known as anti-Hu. ANNA-1 autoimmunity often manifests with multifocal neurological presentations. Typical presentations include neuropathies (mixed sensorimotor, sensory neuronopathy, autonomic neuropathy including gastrointestinal dysmotility/pseudo-obstruction or others), limbic encephalitis, cerebellar ataxia, encephalomyelitis, and myelopathy. Small-cell lung carcinoma (SCLC) or other neuroendocrine tumors are almost always present in older adults, often as limited-stage disease. Extrapulmonary primary small-cell carcinoma, such as tumors of the skin, larynx, tongue, breast, cervix, prostate, endocrine, or pancreas, should be considered, especially in patients who do not smoke. Autopsy sometimes reveals SCLC in patients who lack evidence of tumor in life. In pediatric populations, neuroblastoma is sometimes encountered as the pertinent neoplasm. Other malignancies have also rarely been reported; in 15% of patients with confirmed SCLC, an unrelated and more apparent primary malignancy coexists with SCLC.
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
PCDEC / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Spinal Fluid
<1:2
Interpretation
Antineuronal nuclear antibody type 1 (ANNA-1) is highly specific for the presence of a paraneoplastic neurological syndrome and/or cancer. It has been detected in patients with small-cell lung carcinoma (SCLC) without evidence of neurological autoimmunity. It is detected before SCLC is diagnosed in half of the cases, and its presence suggests that the patient's neurological presentation is paraneoplastic. It is specific for the HuD or ELAVL4 antigen.
Cautions
A cancer other than small-cell lung carcinoma (SCLC) may be found first but will coexist with SCLC in 15% of cases. Presence of nonneural specific antibodies in a patient's specimen may hinder interpretation of antineuronal nuclear antibody type 1 (ANNA-1) results by tissue indirect immunofluorescence.
Clinical Reference
1. Lucchinetti CF, Kimmel DW, Lennon VA. Paraneoplastic and oncological and profiles of patients seropositive for type 1 antineuronal nuclear autoantibodies. Neurology. 1998;50(3):652-657
2. Vernino S, Eggenberger ER, Rogers LR, Lennon VA. Paraneoplastic neurological autoimmunity associated with ANNA-1 autoantibody and thymoma. Neurology. 2002;59(6):929-932
3. Pranzatelli MR, McGee NR. Neuroimmunology of OMS and ANNA-1/anti-Hu paraneoplastic syndromes in a child with neuroblastoma. Neurol Neuroimmunol Neuroinflamm. 2017;5(2):e433. doi:10.1212/NXI.0000000000000433
4. Horta ES, Lennon VA, Lachance DH, et al. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014;20(14):3862-3869
5. Zekeridou A. Paraneoplastic Neurologic Disorders. Continuum (Minneap Minn). 2024;30(4):1021-1051. doi:10.1212/CON.0000000000001449
6. Paramasivan NK, Masoud M, Karsten C, et al. Phenotypic and oncological insights in ANNA1 autoimmunity: Age stratification and biomarker analysis. Ann Clin Transl Neurol. 2025;12(2):280-290. doi:10.1002/acn3.52254
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)
Day(s) Performed
Monday through Sunday
Report Available
6 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 |
|---|---|---|
| AN1TC | ANNA-1 Titer, CSF | 94356-3 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 43440 | ANNA-1 Titer, CSF | 94356-3 |