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Test Code MA2EC Ma2 Antibody, ELISA, Spinal Fluid


Necessary Information


Provide the following information:

1. Relevant clinical information

2. Ordering provider name, phone number, mailing address, and e-mail address



Specimen Required


Container/Tube: Sterile vial

Preferred: Vial number 1

Acceptable: Any vial

Specimen Volume: 2 mL


Useful For

Evaluating patients with suspected paraneoplastic encephalitides using spinal fluid specimens

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)

Reporting Name

Ma2 Ab ELISA, CSF

Specimen Type

CSF

Specimen 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

Ma2 antibodies are IgG biomarkers found in patients with paraneoplastic encephalitis (limbic encephalitis or brainstem encephalitis) or cerebellar ataxia. Antibodies (Ab) to Ma antigens can be found directed at Ma2 alone, or both Ma1 and Ma2, but never Ma1 alone. The accompanying neurological disorders (encephalitis, dementia, brainstem encephalitis, cerebellar ataxia) are usually severe. The cancer associations are either testicular germinoma (Ma2 Ab positive only) or diverse (Ma1 and Ma2 Ab positive). Neurological improvement upon treatment of cancer or immunotherapy is more commonly encountered in those seropositive for Ma2 only than when compared to Ma1 and Ma2 together.

Reference Values

Negative

Interpretation

Seropositivity for Ma2 antibody is consistent with a diagnosis of an autoimmune central nervous system disorder (encephalopathy, dementia, seizure disorder, brainstem encephalitis or cerebellar ataxia). A paraneoplastic basis should be considered and include seminoma (testicular or extra-testicular).

Cautions

A negative Ma2 antibody test result does not exclude autoimmune neurological disease or cancer.

Clinical Reference

1. Voltz R, Gultekin SH, Rosenfeld MR, et al: A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med. 1999 Jun 10;340(23):1788-1795. doi: 10.1056/NEJM199906103402303

2. Rosenfeld MR, Eichen JG, Wade DF, Posner JB, Dalmau J: Molecular and clinical diversity in paraneoplastic immunity to Ma proteins. Ann Neurol. 2001 Sep;50(3):339-348

3. Dalmau J, Graus F, Villarejo A, et al: Clinical analysis of anti-Ma2-associated encephalitis. Brain. 2004 Aug;127(Pt 8):1831-1844. doi: 10.1093/brain/awh203

4. Schuller M, Jenne D, Voltz R. The human PNMA family: novel neuronal proteins implicated in paraneoplastic neurological disease. J Neuroimmunol. 2005 Dec;169(1-2):172-176. doi: 10.1016/j.jneuroim.2005.08.019

5. Hoffmann LA, Jarius S, Pellkofer HL, et al: Anti-Ma and anti-Ta associated paraneoplastic neurological syndromes: 22 newly diagnosed patients and review of previous cases. J Neurol Neurosurg Psychiatry. 2008 Jul;79(7):767-773. doi: 10.1136/jnnp.2007.118588

6. Kunchok A, McKeon A: Opsoclonus in anti-Ma2 brain-stem encephalitis. N Engl J Med. 2020 Sep 24;383(13):e84. doi: 10.1056/NEJMicm1914516

7. Adams C, McKeon A, Silber MH, Kumar R: Narcolepsy, REM sleep behavior disorder, and supranuclear gaze palsy associated with Ma1 and Ma2 antibodies and tonsillar carcinoma. Arch Neurol. 2011 Apr;68(4):521-4. doi: 10.1001/archneurol.2011.56. Erratum in: Arch Neurol. 2011 Sep;68(9):1211

Method Description

Ma2 antibodies are directed against their corresponding intracellular protein (PNMA2). The Ma2 autoantibody enzyme-linked immunosorbent assay (ELISA) is based on the principle of indirect ELISA that employs the ability of Ma2 autoantibodies to bind to antigenic protein (PNMA2) coated on the well surface of an ELISA plate. Detection of this bound antibody is accomplished using an antihuman secondary antibody that specifically recognizes the Fc region of the bound autoantibody. The secondary antibody is conjugated with alkaline phosphatase that enzymatically hydrolyzes a substrate molecule to produce an end product with a yellow color measurable at a wavelength of 405 nm. Controls and diluted samples are added in duplicate to coated plate wells and incubated for 2 hours, then washed extensively before adding the conjugated secondary antibody for an additional hour. After aspiration and washing, p-nitrophenyl phosphate substrate is added to each well and incubated for an additional hour before absorbance is measured at 405 nm.(Instruction manual: Capture ELISA Protocols. Abnova; R 1.1, 02/2011)

Day(s) Performed

Tuesday, Friday

Report Available

3 to 5 days

Specimen Retention Time

28 days

Performing 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

83516

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MA2EC Ma2 Ab ELISA, CSF 101867-0

 

Result ID Test Result Name Result LOINC Value
605971 Ma2 Ab ELISA, CSF 101867-0

NY State Approved

Yes