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HelpTest Code PAC1 Paraneoplastic, Autoantibody Evaluation, Spinal Fluid
Reporting Name
Paraneoplas Autoantibody Eval,CSFUseful For
Aiding in the diagnosis of paraneoplastic neurological autoimmune disorders related to carcinoma of lung, breast, ovary, thymoma, or Hodgkin lymphoma using spinal fluid specimens
Profile Information
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| PNEOI | Paraneoplastic Interpretation, CSF | No | Yes |
| AMPHC | Amphiphysin Ab, CSF | No | Yes |
| AGN1C | Anti-Glial Nuclear Ab, Type 1 | No | Yes |
| ANN1C | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
| ANN2C | Anti-Neuronal Nuclear Ab, Type 2 | No | Yes |
| ANN3C | Anti-Neuronal Nuclear Ab, Type 3 | No | Yes |
| CRMC | CRMP-5-IgG, CSF | No | Yes |
| PCTRC | Purkinje Cell Cytoplasmc Ab Type Tr | No | Yes |
| PCA1C | Purkinje Cell Cytoplasmic Ab Type 1 | No | Yes |
| PCA2C | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
Reflex Tests
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| AGNBC | AGNA-1 Immunoblot, CSF | No | No |
| AMIBC | Amphiphysin Immunoblot, CSF | No | No |
| AN1BC | ANNA-1 Immunoblot, CSF | No | No |
| AN2BC | ANNA-2 Immunoblot, CSF | No | No |
| CRMWC | CRMP-5-IgG Western Blot, CSF | Yes | No |
| PC1BC | PCA-1 Immunoblot, CSF | No | No |
| PCTBC | PCA-Tr Immunoblot, CSF | No | No |
| AGNTC | AGNA-1 Titer, CSF | No | No |
| AN1TC | ANNA-1 Titer, CSF | No | No |
| AN2TC | ANNA-2 Titer, CSF | No | No |
| AN3TC | ANNA-3 Titer, CSF | No | No |
| APHTC | Amphiphysin Ab Titer, CSF | No | No |
| CRMTC | CRMP-5-IgG Titer, CSF | No | No |
| PC1TC | PCA-1 Titer, CSF | No | No |
| PC2TC | PCA-2 Titer, CSF | No | No |
| PCTTC | PCA-Tr Titer, CSF | No | No |
Testing Algorithm
If the indirect immunofluorescence assay (IFA) pattern suggests AGNA-1 antibody, then AGNA-1 immunoblot (IB) and AGNA-1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests antineuronal nuclear antibody type 1 (ANNA-1), then ANNA-1 IB, ANNA-1 IFA titer, and ANNA-2 IB will be performed at an additional charge.
If the IFA pattern suggests ANNA-2 antibody, then ANNA-2 IB, ANNA-2 IFA titer, and ANNA-1 IB will be performed at an additional charge.
If the IFA pattern suggests ANNA-3 antibody, then ANNA-3 titer will be performed at an additional charge.
If the IFA pattern suggests Purkinje cytoplasmic antibody type 1 (PCA-1), then PCA-1 IB, and PCA-1 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-2 antibody, then PCA-2 IFA titer will be performed at an additional charge.
If the IFA pattern suggests PCA-Tr antibody, then PCA-Tr immunoblot, and PCA-Tr IFA titer will be performed at an additional charge.
If client requests or the IFA patterns suggest CRMP-5-IgG, then CRMP-5-IgG IFA titer and CRMP-5-IgG western blot will be performed at an additional charge.
If the IFA patterns suggest amphiphysin antibody, then amphiphysin IB and amphiphysin IFA titer will be performed at an additional charge.
The following algorithm is available: Paraneoplastic Evaluation Algorithm-Spinal Fluid.
Method Name
AGN1C, AMPHC, ANN1C, ANN2C, ANN3C, CRMC, PCA1C, PCA2C7, PCTRC, AGNTC, APHTC, AN1TC, AN2TC, AN3TC, CRMTC, PC1TC, PC2TC, PCTTC: Indirect Immunofluorescence Assay (IFA)
CRMWC: Western Blot
AGNBC, AMIBC, AN1BC, AN2BC, PC1BC, PCTBC: Immunoblot (IB)
Performing Laboratory
Mayo Clinic Laboratories in Rochester
Specimen Type
CSFOrdering Guidance
This test no longer contains all known, clinically relevant antibodies for patients suspected of autoimmune neurological disorders. Instead, consider a comprehensive neurological phenotype-specific autoimmune/paraneoplastic evaluation (eg, encephalopathy, movement disorders, myelopathy, axonal neuropathy). For more information as well as phenotype-specific testing options, refer to Autoimmune Neurology Test Ordering Guide or the Neurology specialty website.
Additional Testing Requirements
In patients with a history of tobacco use or other lung cancer risk, or if thymoma is suspected, PAVAL / Paraneoplastic Autoantibody Evaluation, Serum is also recommended.
Necessary Information
Provide the following information:
-Relevant clinical information
-Ordering provider name, phone number, mailing address, and e-mail address
Specimen Required
Container/Tube: Sterile vial
Preferred: Vial number 2
Acceptable: Any vial
Specimen Volume: 4 mL
Specimen Minimum Volume
2 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 |
Special Instructions
Reference Values
|
Test ID |
Reporting name |
Methodology |
Reference value |
|
AMPHC |
Amphiphysin Ab, CSF |
IFA |
Negative |
|
AGN1C |
Anti-Glial Nuclear Ab, Type 1 |
IFA |
Negative |
|
ANN1C |
Anti-Neuronal Nuclear Ab, Type 1 |
IFA |
Negative |
|
ANN2C |
Anti-Neuronal Nuclear Ab, Type 2 |
IFA |
Negative |
|
ANN3C |
Anti-Neuronal Nuclear Ab, Type 3 |
IFA |
Negative |
|
CRMC |
CRMP-5-IgG, CSF |
IFA |
Negative |
|
PCTRC |
Purkinje Cell Cytoplasmc Ab Type Tr |
IFA |
Negative |
|
PCA1C |
Purkinje Cell Cytoplasmic Ab Type 1 |
IFA |
Negative |
|
PCA2C |
Purkinje Cell Cytoplasmic Ab Type 2 |
IFA |
Negative |
Reflex Information:
|
Test ID |
Reporting name |
Methodology |
Reference value |
|
AGNBC |
AGNA-1 Immunoblot, CSF |
IB |
Negative |
|
AGNTC |
AGNA-1 Titer, CSF |
IFA |
<1:2 |
|
AMIBC |
Amphiphysin Immunoblot, CSF |
IB |
Negative |
|
AN1BC |
ANNA-1 Immunoblot, CSF |
IB |
Negative |
|
AN1TC |
ANNA-1 Titer, CSF |
IFA |
<1:2 |
|
AN2BC |
ANNA-2 Immunoblot, CSF |
IB |
Negative |
|
AN2TC |
ANNA-2 Titer, CSF |
IFA |
<1:2 |
|
AN3TC |
ANNA-3 Titer, CSF |
IFA |
<1:2 |
|
APHTC |
Amphiphysin Ab Titer, CSF |
IFA |
<1:2 |
|
CRMTC |
CRMP-5-IgG Titer, CSF |
IFA |
<1:2 |
|
CRMWC |
CRMP-5-IgG Western Blot, CSF |
WB |
Negative |
|
PC1BC |
PCA-1 Immunoblot, CSF |
IB |
Negative |
|
PC1TC |
PCA-1 Titer, CSF |
IFA |
<1:2 |
|
PC2TC |
PCA-2 Titer, CSF |
IFA |
<1:2 |
|
PCTBC |
PCA-Tr Immunoblot, CSF |
IB |
Negative |
|
PCTTC |
PCA-Tr Titer, CSF |
IFA |
<1:2 |
*Methodology abbreviations:
Immunofluorescence assay (IFA)
Western blot (WB)
Immunoblot (IB)
Neuron-restricted patterns of IgG staining that do not fulfill criteria for amphiphysin, ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, or CRMP-5-IgG may be reported as "unclassified antineuronal IgG." Complex patterns that include non-neuronal elements may be reported as "uninterpretable."
Note: Titers lower than 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (held 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call 800-533-1710 to request CRMP-5 Western blot.
Day(s) Performed
Profile tests: Monday through Sunday; Reflex tests: Varies
CPT Code Information
86255 x 9
84182-AGNBC (if appropriate)
86256-AGNTC (if appropriate)
84182-AMIBC (if appropriate)
84182-AN1BC (if appropriate)
86256-AN1TC (if appropriate)
84182-AN2BC (if appropriate)
86256-AN2TC (if appropriate)
86256-AN3TC (if appropriate)
86256-APHTC (if appropriate)
86256-CRMTC (if appropriate)
84182-CRMWC (if appropriate)
84182-PC1BC (if appropriate)
86256-PC1TC (if appropriate)
86256-PC2TC (if appropriate)
84182-PCTBC (if appropriate)
86256-PCTTC (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| PAC1 | Paraneoplas Autoantibody Eval,CSF | 94818-2 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 89079 | AGNA-1, CSF | 90827-7 |
| 5906 | Amphiphysin Ab, CSF | 90815-2 |
| 3852 | ANNA-1, CSF | 44768-0 |
| 7472 | ANNA-2, CSF | 56959-0 |
| 21633 | ANNA-3, CSF | 90836-8 |
| 21650 | CRMP-5-IgG, CSF | 63216-6 |
| 3988 | PCA-1, CSF | 90841-8 |
| 21632 | PCA-2, CSF | 90843-4 |
| 21631 | PCA-Tr, CSF | 90845-9 |
| 34271 | Paraneoplastic Interpretation, CSF | 57771-8 |
| 619519 | IFA Notes | 48767-8 |
Clinical Information
Several antineuronal and glial autoantibodies are recognized clinically as markers of a patient's immune response to specific cancers (paraneoplastic autoantibodies). Seropositive patients present with neurologic signs and symptoms in more than 90% of cases. The cancers are most commonly small-cell lung carcinoma, ovarian (or related mullerian) carcinoma, breast carcinoma, thymoma, or Hodgkin lymphoma. The cancers may be new or recurrent, are usually limited in metastatic volume, and are often occult by standard imaging procedures. Detection of the informative marker autoantibodies allows early diagnosis and treatment of the cancer, which may lessen neurological morbidity and improve survival.
Serum is the preferred specimen for paraneoplastic autoantibodies. However, cerebrospinal fluid (CSF) results are sometimes positive when serum results are negative (especially for collapsin response-mediator protein-5-IgG [CRMP-5] and other inflammatory central nervous system autoimmunity). Additionally, CSF is more readily interpretable because it generally lacks the interfering nonorgan-specific antibodies that are common in the serum of patients with cancer. Because neurologists typically perform spinal taps in these patients, the recommendation is to submit CSF specimens with serum specimens, either for simultaneous testing or to be held for testing only if serum is negative.
CRMP-5-IgG western blot is also performed by specific request for more sensitive detection of CRMP-5-IgG. Testing should be requested in cases of subacute basal ganglionic disorders (chorea, parkinsonism), cranial neuropathies (especially loss of vision, taste, or smell), and myelopathies.
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. Conversely, a positive autoantibody profile has 80% to 90% predictive value for a specific cancer. It is not uncommon for more than one paraneoplastic autoantibody to be detected, each predictive of the same cancer.
Cautions
No significant cautionary statements
Clinical Reference
1. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1 anti-neuronal nuclear antibody. Neurology. 1998 Mar;50(3):652-657
2. 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
3. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol. 2003 May;53(5):580-587
4. Chan KH, Vernino S, Lennon VA: ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol. 2001 Sep;50(3):301-311
5. Hetzel DJ, Stanhope CR, O'Neill BP, Lennon VA: Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-Purkinje cell antibodies and limited in metastatic volume. Mayo Clin Proc. 1990 Dec;65(12):1558-1563
6. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol. 2005 Jul;58(1):96-107
7. McKeon A, Pittock SJ: Paraneoplastic encephalomyelopathies: pathology and mechanisms. Acta Neuropathol. 2011 Oct;122(4):381-400
8. 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
Indirect Immunofluorescence Assay (IFA):
The patient's sample is tested by a standardized immunofluorescence assay (IFA) 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.0000000000000385689)
Western Blot:
Neuronal antigens extracted aqueously from adult rat cerebellum, full-length recombinant human collapsin response-mediator protein-5 (CRMP-5), or full-length recombinant human amphiphysin protein is denatured, reduced, and separated by electrophoresis on 10% polyacrylamide gel. IgG is detected autoradiographically by enhanced chemiluminescence.(Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol. 2001 Feb;49[2]:146-154; Dubey D, Jitprapaikulsan J, Bi H, et al: Amphiphysin-IgG autoimmune neuropathy: A recognizable clinicopathologic syndrome. Neurology. 2019 Nov 12;93(20):e1873-e1880
Immunoblot (IB):
All steps are performed at ambient temperature (18-28° C) utilizing the EUROBlot One instrument. Diluted patient serum (1:12.5) is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive specimens will bind to the purified recombinant antigen and negative specimens will not bind. Strips are washed to remove unbound antibodies and then incubated with anti-human IgG antibodies (alkaline phosphatase-labelled) for 30 minutes. The strips are again washed to remove unbound anti-human IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolylphosphate (NBT/BCIP) 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 Apr 4;6[3]:e552. doi: 10.1212/NXI.0000000000000552)