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Test ID: PNEOE    
Paraneoplastic Autoantibody Evaluation, Spinal Fluid

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Useful For Suggests clinical disorders or settings where the test may be helpful

Aids in the diagnosis of paraneoplastic neurological autoimmune disorders related to carcinoma of lung, breast, ovary, thymoma, or Hodgkin lymphoma

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

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 symptoms and signs in >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 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 serum of patients with cancer. Because neurologists typically perform spinal taps in these patients, we recommend that CSF be submitted with serum, 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.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

NEURONAL NUCLEAR ANTIBODIES

Antineuronal Nuclear Antibody-Type 1 (ANNA-1)

Negative at <1:2

Antineuronal Nuclear Antibody-Type 2 (ANNA-2)

Negative at <1:2

Antineuronal Nuclear Antibody-Type 3 (ANNA-3)

Negative at <1:2

Anti-Glial/Neuronal Nuclear Antibody-Type 1 (AGNA-1)

Negative at <1:2

 

NEURONAL AND MUSCLE CYTOPLASMIC ANTIBODIES

Purkinje Cell Cytoplasmic Antibody, Type 1 (PCA-1)

Negative at <1:2

Purkinje Cell Cytoplasmic Antibody, Type 2 (PCA-2)

Negative at <1:2

Purkinje Cell Cytoplasmic Antibody, Type TR (PCA-TR)

Negative at <1:2

Amphiphysin Antibody

Negative at <1:2

Collapsin Response-Mediator Protein-5 Neuronal (CRMP-5-IGG)

Negative at <1:2

 

ISLET CELL ANTIBODIES

Glutamic Acid Decarboxylase (GAD65) Antibody Assay

< or =0.02 nmol/L

 

WESTERN BLOT

Paraneoplastic Western Blot

Negative

CRMP-5-IgG Western Blot         

Negative

Amphiphysin Western Blot       

Negative                                                 

 

N-Methyl-D-aspartate receptor (NMDA-R)                                

CBA: Negative

IFA <1:2

2-amino-3-(5-methyl-3-oxo-1,2- oxazol-4-yl) propanoic acid receptor (AMPA-R)    

CBA: Negative

IFA <1:2

Gamma-Amino Butyric acid-type B receptor (GABA-B-R)

CBA: Negative

IFA <1:2

NMO/AQP4-IgG

Negative

VGKC-Complex Antibody IPA

< or=0.02 nmol/L                       

Interpretation Provides information to assist in interpretation of the test results

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 symptoms and signs. 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 1 paraneoplastic autoantibody to be detected, each predictive of the same cancer.

 

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.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

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 symptoms and signs. 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 1 paraneoplastic autoantibody to be detected, each predictive of the same cancer.

 

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.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1 anti-neuronal nuclear antibody. Neurology 1998;50:652-657

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;154(1-2):166-171

3. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003;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 September;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;65:1558-1563

6. Vernino S, Lennon VA: New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000 March;47(3):297-305

7. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005;58(1):96-107

8. Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49(2):146-154

Special Instructions and Forms Describes specimen collection and preparation information, test algorithms, and other information pertinent to test. Also includes pertinent information and consent forms to be used when requesting a particular test