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HelpTest Code AGNTC Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1) Titer, Spinal Fluid
Ordering Guidance
Serum is preferred; see AGN1S / Anti-Glial/Neuronal Nuclear Antibody-Type 1, Serum.
Spinal fluid is particularly useful if interfering antibodies are present.
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
Container/Tube: Sterile vial
Specimen Volume: 2 mL
Useful For
Reporting an end titer result from cerebrospinal fluid (CSF) specimens
Serological evaluation using CSF specimens from 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 by metastasis
Differentiating autoimmune neuropathies from neurotoxic effects of chemotherapy
Monitoring the immune response of seropositive patients during cancer therapy
Detecting early evidence of cancer recurrence in previously seropositive patients
Testing Algorithm
If the indirect immunofluorescence pattern suggests anti-glial/neuronal nuclear antibody-type 1 (AGNA-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
Indirect Immunofluorescence Assay (IFA)
Reporting Name
AGNA-1 Titer, CSFSpecimen Type
CSFSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| 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
Anti-glial/neuronal nuclear autoantibody-type 1 (AGNA-1) is recognized clinically as a marker of a patient's immune response to a lung cancer that is usually limited in metastasis but manifests as an autoimmune neurological disorder.
AGNA-1 is an IgG marker of an immune response to cancer (usually a small-cell lung carcinoma: SCLC) in patients presenting with a subacute, generally multifocal, paraneoplastic neurological disorder.(1-3) It binds to the nucleus, but not cytoplasm, of SCLC cell lines and, in the adult central nervous system, to nuclei in subsets of astrocytes and neurons, as well as ependyma. Its previous name was antineuronal nuclear antibody (ANNA)-4.(2) The most common neurological presentations of patients who are positive for AGNA-1 are Lambert-Eaton myasthenic syndrome, sensorimotor or autonomic neuropathy, limbic encephalopathy, and ataxias.
To date, all 45 seropositive patients identified in the Mayo Clinic Neuroimmunology Laboratory have been smokers. SCLC was confirmed in more than 80% of cases. In 59% of patients, one or more identifiable coexisting paraneoplastic autoantibodies support the prediction of SCLC: P/Q-type Ca(++) channel antibody (41%) greater than collapsin response-mediator protein-5 (CRMP-5)-IgG equal to ANNA-1 greater than other antibodies.
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
Neuron-restricted patterns of IgG staining that do not fulfill criteria for anti-glial/neuronal nuclear antibody-type 1 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 the patient's subacute neurological disorder has an autoimmune basis and predicts with greater than 80% certainty that the patient has a lung carcinoma (usually small-cell lung carcinoma: SCLC), either new or recurrent, and confined to the chest. Fifteen percent of seropositive patients who are eventually proven to have SCLC additionally have an unrelated, often more obvious, cancer, either coexisting or by past history.
Anti-glial/neuronal nuclear autoantibody-type 1 (AGNA-1) has not been encountered in healthy subjects (n=170). Its onconeural antigen is the nuclear transcription factor Sox1.(2) IgG of this specifically has been reported detectable in 30% to 40% of patients with SCLC who lack neurological complications.(4)
Cautions
Anti-glial/neuronal nuclear autoantibody-type 1 (AGNA-1) is difficult to detect by immunofluorescence when it coexists with other neuronal nuclear autoantibodies, such as antineuronal nuclear antibody (ANNA)-1 or ANNA-2, unless the titer of AGNA-1 exceeds that of the coexisting autoantibodies. It has not been detected by Western blot.(1)
Clinical Reference
1. Graus F, Vincent A, Pozo-Rosich P, et al: Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic neurological syndromes. J Neuroimmunol. 2005 Aug;165(1-2):166-171
2. Lachance D, Kryzer TJ, Pittock SJ, et al: Anti-neuronal nuclear antibody type 4 (ANNA-4), a novel paraneoplastic marker of small-cell lung carcinoma (SCLC). Neurology. 2006;66 (Suppl 2):A340
3. Sabater L, Saiz A, Titulaer MG, et al: Sox1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology. 2008 Mar 18;70(12):924-928
4. Gure AO, Stockert E, Scanlan MJ, et al: Serological identification of embryonic neural proteins as highly immunogenic tumor antigens in small cell lung cancer. Proc Natl Acad Sci USA. 2000 Apr 11;97(8):4198-4203
5. McKeon A, Pittock SJ: Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol. 2011 Oct;122(4):381-400
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
7. Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004 Nov;56(5):715-719
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)
Day(s) Performed
Monday through Sunday
Report Available
6 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 |
|---|---|---|
| AGNTC | AGNA-1 Titer, CSF | 93455-5 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 43443 | AGNA-1 Titer, CSF | 94355-5 |