Test Code AIAES Axonal Neuropathy, Autoimmune/Paraneoplastic Evaluation, Serum
Additional Codes
DRAW TWO 5.0 ML PLAIN RED TUBES
Ordering Guidance
Multiple neurological phenotype-specific autoimmune/paraneoplastic evaluations are available. For more information as well as phenotype-specific testing options, see Autoimmune Neurology Test Ordering Guide.
When more than one evaluation is ordered on the same order number, the duplicate test will be canceled.
For a list of antibodies performed with each evaluation, see Autoimmune Neurology Antibody Matrix.
This test should not be requested for patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given, and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held 1 week and assayed if sufficiently decayed or canceled if radioactivity remains.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering provider name, phone number, mailing address, and e-mail address
Specimen Required
Patient Preparation:
For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin (IVIg) treatment.
Supplies: Sarstedt Aliquot Tube, 5 mL (T914)
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 4 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Secondary ID
606974Useful For
Evaluation of patients who present with a subacute neurological disorder of undetermined etiology, especially those with known risk factors for cancer
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
Detecting early evidence of cancer recurrence in previously seropositive patients
Profile Information
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AIAEI | Autoimmune Axonal Interp, S | No | Yes |
AMPHS | Amphiphysin Ab, S | No | Yes |
ANN1S | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
ANN3S | Anti-Neuronal Nuclear Ab, Type 3 | No | Yes |
AGN1S | Anti-Glial Nuclear Ab, Type 1 | No | Yes |
APBIS | AP3B2 IFA, S | No | Yes |
CS2CS | CASPR2-IgG CBA, S | No | Yes |
CRMWS | CRMP-5-IgG Western Blot, S | Yes | Yes |
GFAIS | GFAP IFA, S | No | Yes |
IG5CS | IgLON5 CBA, S | No | Yes |
LG1CS | LGI1-IgG CBA, S | No | Yes |
NIFIS | NIF IFA, S | No | Yes |
PCABP | Purkinje Cell Cytoplasmic Ab Type 1 | No | Yes |
PCAB2 | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
Reflex Tests
Test ID | Reporting Name | Available Separately | Always Performed |
---|---|---|---|
AGNBS | AGNA-1 Immunoblot, S | No | No |
AINCS | Alpha Internexin CBA, S | No | No |
AMIBS | Amphiphysin Immunoblot, S | No | No |
AN1BS | ANNA-1 Immunoblot, S | No | No |
AN1TS | ANNA-1 Titer, S | No | No |
AN2BS | ANNA-2 Immunoblot, S | No | No |
AN3TS | ANNA-3 Titer, S | No | No |
APBCS | AP3B2 CBA, S | No | No |
APBTS | AP3B2 IFA Titer, S | No | No |
APHTS | Amphiphysin Ab Titer, S | No | No |
CRMTS | CRMP-5-IgG Titer, S | No | No |
GFACS | GFAP CBA, S | No | No |
GFATS | GFAP IFA Titer, S | No | No |
NFHCS | NIF Heavy Chain CBA, S | No | No |
NFLCS | NIF Light Chain CBA, S | No | No |
NIFTS | NIF IFA Titer, S | No | No |
PC1BS | PCA-1 Immunoblot, S | No | No |
PC1TS | PCA-1 Titer, S | No | No |
PC2TS | PCA-2 Titer, S | No | No |
AGNTS | AGNA-1 Titer, S | No | No |
IG5TS | IgLON5 IFA Titer, S | No | No |
Testing Algorithm
If the indirect immunofluorescence assay (IFA) patterns suggest antiglial nuclear antibody-1 (AGNA-1), then the AGNA-1 antibody IFA titer and AGNA-1 antibody immunoblot will be performed at an additional charge.
If the IFA patterns suggest antineuronal nuclear antibody type 1 (ANNA-1), then the ANNA-1 IFA titer, ANNA-1 immunoblot, and ANNA-2 immunoblot will be performed at an additional charge.
If the client requests or the IFA pattern suggests ANNA-3 antibody, then the ANNA-3 IFA titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then the PCA-1 antibody IFA titer and PCA-1 antibody immunoblot will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then the PCA-2 antibody IFA titer will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then the amphiphysin antibody IFA titer and amphiphysin antibody immunoblot will be performed at an additional charge.
If the IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then the GFAP antibody cell binding assay (CBA) and GFAP antibody IFA titer will be performed at an additional charge.
If the collapsin response-mediator protein-5 (CRMP-5)-IgG antibody Western blot is positive, then the CRMP-5-IgG antibody IF titer will be performed at an additional charge.
If the IFA pattern suggests adaptor protein 3 beta 2 (AP3B2) antibody, then the AP3B2 antibody IFA titer and AP3B2 antibody CBA will be performed at an additional charge.
If the IFA pattern suggests neuronal intermediate filament (NIF) antibody, then the alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF IFA titer will be performed at an additional charge.
If the IgLON family member 5 antibody (IgLON5) by CBA result is positive, then the IgLON5 antibody IFA titer will be performed at an additional charge.
For more information see:
-Autoimmune/Paraneoplastic Axonal Neuropathy Evaluation Algorithm.
Method Name
APBCS, CS2CS, LG1CS, AINCS, NFLCS, NFHCS, GFACS, IG5CS: Cell Binding Assay (CBA)
AGN1S, AGNTS, AMPHS, APHTS, ANN1S, AN1TS, ANN3S, AN3TS, APBIS, APBTS, NIFIS, NIFTS, PCABP, PCAB2, PC1TS, PC2TS, GFAIS, GFATS, CRMTS, IG5TS: Indirect Immunofluorescence Assay (IFA)
CRMWS; Western Blot (WB)
AGNBS, AMIBS, AN1BS, PC1BS, AN2BS: Immunoblot (IB)
Specimen Type
SerumSpecimen Minimum Volume
2 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 |
Reference Values
Test ID |
Reporting name |
Methodology |
Reference value |
AIAEI |
Autoimmune Axonal Interp, S |
Medical interpretation |
NA |
AGN1S |
Anti-Glial Nuclear Ab, Type 1 |
IFA |
Negative |
AMPHS |
Amphiphysin Ab, S |
IFA |
Negative |
ANN1S |
ANNA-1, S |
IFA |
Negative |
ANN3S |
ANNA-3, S |
IFA |
Negative |
APBIS |
AP3B2 IFA, S |
IFA |
Negative |
CRMWS |
CRMP-5-IgG Western Blot, S |
WB |
Negative |
CS2CS |
CASPR2-IgG CBA, S |
CBA |
Negative |
IG5CS |
IgLON5 CBA, S |
CBA |
Negative |
LG1CS |
LGI1-IgG CBA, S |
CBA |
Negative |
NIFIS |
NIF IFA, S |
IFA |
Negative |
PCAB2 |
PCA-2, S |
IFA |
Negative |
PCABP |
PCA-1, S |
IFA |
Negative |
GFAIS |
GFAP IFA, S |
IFA |
Negative |
Reflex Information:
Test ID |
Reporting name |
Methodology |
Reference value |
AGNBS |
AGNA-1 Immunoblot, S |
IB |
Negative |
AGNTS |
AGNA-1 Titer, S |
IFA |
<1:240 |
AINCS |
Alpha Internexin CBA, S |
CBA |
Negative |
AMIBS |
Amphiphysin Immunoblot, S |
IB |
Negative |
AN1BS |
ANNA-1 Immunoblot, S |
IB |
Negative |
AN1TS |
ANNA-1 Titer, S |
IFA |
<1:240 |
AN2BS |
ANNA-2 Immunoblot, S |
IB |
Negative |
AN3TS |
ANNA-3 Titer, S |
IFA |
<1:240 |
APBCS |
AP3B2 CBA, S |
CBA |
Negative |
APBTS |
AP3B2 IFA Titer, S |
IFA |
<1:240 |
APHTS |
Amphiphysin Ab Titer, S |
IFA |
<1:240 |
CRMTS |
CRMP-5-IgG Titer, S |
IFA |
<1:240 |
GFACS |
GFAP CBA, S |
CBA |
Negative |
GFATS |
GFAP IFA Titer, S |
IFA |
<1:240 |
IG5TS |
IgLON5 IFA Titer, S |
IFA |
<1:240 |
NFHCS |
NIF Heavy Chain CBA, S |
CBA |
Negative |
NFLCS |
NIF Light Chain CBA, S |
CBA |
Negative |
NIFTS |
NIF IFA Titer, S |
IFA |
<1:240 |
PC1BS |
PCA-1 Immunoblot, S |
IB |
Negative |
PC1TS |
PCA-1 Titer, S |
IFA |
<1:240 |
PC2TS |
PCA-2 Titer, S |
IFA |
<1:240 |
*Methodology abbreviations:
Immunofluorescence assay (IFA)
Cell-binding assay (CBA)
Western blot (WB)
Immunoblot (IB)
Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, CRMP-5-IgG, PCA-1, or PCA-2 may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."
Interpretation
Antibodies directed at onconeural proteins shared by neurons, glia, muscle, and certain cancers are valuable serological markers of a patient's immune response to cancer. They are not found in healthy subjects and are usually accompanied by subacute neurological signs and symptoms. Several autoantibodies have a syndromic association, but no autoantibody predicts a specific neurological syndrome. More than one paraneoplastic autoantibody may be detected and associated with specific cancers.
Method Description
Cell-Binding Assay:
Patient sample is applied to a composite slide containing transfected and nontransfected HEK-293 cells. After incubation and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the presence of patient IgG binding.(Package insert: IIFT: Neurology Mosaics, Instructions for the indirect immunofluorescence test. EUROIMMUN; FA_112d-1_A_UK_C13, 02/2019)
Indirect Immunofluorescence Assay:
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;4[5]:e385. doi:10.1212/NXI.0000000000000385)
Western Blot:
Full-length recombinant human collapsin response mediator protein 5 (CRMP-5) antigen is used to detect CRMP-5-IgG using traditional western blot.(Yu Z, Kryzer TJ, Griesmann GE, et al. CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001;49[2]:145-154; Dubey D, Jitprapaikulsan J, Bi H, et al. Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019;93[20]:e1873-e1880. doi:10.1212/WNL.0000000000008472)
Immunoblot:
All steps are performed at ambient temperature (18-28° C) utilizing the EUROBlot One instrument. Diluted patient serum is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive serum samples will bind to the purified recombinant antigen and negative serum samples will not bind. Strips are washed to remove unbound serum antibodies and then are incubated with antihuman IgG antibodies (alkaline phosphatase-labelled) for 30 minutes. The strips are again washed to remove unbound antihuman IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolylphosphate substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produces a black band. Strips are digitized via picture capture on the EUROBlot One instrument and evaluated with the EUROLineScan software.(O'Connor K, Waters P, Komorowski L, et al. GABAA receptor autoimmunity: A multicenter experience. Neurol Neuroimmunol Neuroinflamm. 2019;6[3]:e552. doi:10.1212/NXI.0000000000000552)
Day(s) Performed
Profile tests: Monday through Sunday; Reflex tests: Varies
Report Available
8 to 12 daysSpecimen Retention Time
28 daysPerforming Laboratory
Mayo Clinic Laboratories in RochesterCPT Code Information
86255 x 12
84182
84182 AGNBS (if appropriate)
86256 AGNTS (if appropriate)
86255 AINCS (if appropriate)
84182 AMIBS (if appropriate)
84182 AN1BS (if appropriate)
86256 AN1TS (if appropriate)
84182 AN2BS (if appropriate)
86256 AN3TS (if appropriate)
86255 APBCS (if appropriate)
86256 APBTS (if appropriate)
86256 APHTS (if appropriate)
86256 CRMTS (if appropriate)
86255 GFACS (if appropriate)
86256 GFATS (if appropriate)
86256 IG5TS (if appropriate)
86255 NFHCS (if appropriate)
86255 NFLCS (if appropriate)
86256 NIFTS (if appropriate)
84182 PC1BS (if appropriate)
86256 PC1TS (if appropriate)
86256 PC2TS (if appropriate)
LOINC Code Information
Test ID | Test Order Name | Order LOINC Value |
---|---|---|
AIAES | Axonal, Autoimm/Paraneo, S | 94695-4 |
Result ID | Test Result Name | Result LOINC Value |
---|---|---|
606950 | IgLON5 CBA, S | 96478-3 |
615863 | AP3B2 IFA, S | 101907-4 |
606964 | NIF IFA, S | 96486-6 |
89080 | AGNA-1, S | 84927-3 |
81722 | Amphiphysin Ab, S | 72327-0 |
80150 | ANNA-1, S | 33615-6 |
83137 | ANNA-3, S | 43102-3 |
83107 | CRMP-5-IgG Western Blot, S | 47401-5 |
83138 | PCA-2, S | 84925-7 |
9477 | PCA-1, S | 84924-0 |
64279 | LGI1-IgG CBA, S | 94287-0 |
64281 | CASPR2-IgG CBA, S | 94285-4 |
605155 | GFAP IFA, S | 94346-4 |
606975 | Autoimmune Axonal Interp, S | 69048-7 |
618900 | IFA Notes | 48767-8 |
Special Instructions
Forms
If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.