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Test ID: PNEFS Neuroimmunology Antibody Follow-up, Serum

Reporting Name

Neuroimmunology Ab Follow-up, S

Useful For

Monitoring patients who have previously tested positive for one or more antibodies within the past 5 years in a Mayo Neuroimmunology Laboratory serum evaluation

Clinical Information

Paraneoplastic autoimmune neurological disorders reflect a patient's humoral and cellular immune responses to cancer. The cancer may be new or recurrent, is usually limited in metastatic volume, and is often occult by standard imaging procedures. Autoantibodies specific for onconeural proteins found in the plasma membrane, cytoplasm, and nucleus of neurons or muscle are generated in this immune response and serve as serological markers of paraneoplastic autoimmunity. The most recognized cancers in this context are small-cell lung carcinoma, thymoma, ovarian (or related mullerian) carcinoma, breast carcinoma, and Hodgkin lymphoma. Pertinent childhood neoplasms recognized thus far include neuroblastoma, thymoma, Hodgkin lymphoma, and chondroblastoma. An individual patient's autoantibody profile can predict a specific neoplasm with 90% certainty but not the neurological syndrome.

 

Four classes of autoantibodies are recognized in serum analysis:

-Neuronal nuclear (antineuronal nuclear antibody-type 1 [ANNA-1], ANNA-2, ANNA-3)

-Neuronal and muscle cytoplasmic (Purkinje cell cytoplasmic antibody, type 1 [PCA-1], PCA-2, PCA-Tr, collapsin response-mediator protein-5 [CRMP-5], amphiphysin, and striational)

-Glial nuclear (antiglial nuclear antibody: AGNA)

-Plasma membrane cation channel antibodies (neuronal P/Q-type and muscle acetylcholine receptor autoantibodies). These autoantibodies are potential effectors of neurological dysfunction.

 

Patients who are seropositive usually present with subacute neurological signs and symptoms. The patient may present with encephalopathy, cerebellar ataxia, myelopathy, radiculopathy, plexopathy, sensory, sensorimotor, or autonomic neuropathy, with or without coexisting evidence of a neuromuscular transmission disorder: Lambert-Eaton syndrome, myasthenia gravis, or neuromuscular hyperexcitability. Initial signs may be subtle, but a subacute multifocal and progressive syndrome usually evolves. Sensorimotor neuropathy and cerebellar ataxia are common presentations, but the clinical picture in some patients is dominated by striking gastrointestinal dysmotility, limbic encephalopathy, basal ganglionitis, or cranial neuropathy (especially loss of vision, hearing, smell, or taste). Cancer risk factors include past or family history of cancer, history of smoking, or social/environmental exposure to carcinogens. Early diagnosis and treatment of the neoplasm favor less neurological morbidity and offer the best hope for survival.

Interpretation

Antibodies directed at onconeural proteins shared by neurons, 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 known 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.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
GANG AChR Ganglionic Neuronal Ab, S No No
ACMFS AChR Modulating Flow Cytometry, S No No
AGNBS AGNA-1 Immunoblot, S No No
AINCS Alpha Internexin CBA, S No No
AMPCS AMPA-R Ab CBA, S No No
AMIBS Amphiphysin Immunoblot, S No No
AN1BS ANNA-1 Immunoblot, S No No
AN2BS ANNA-2 Immunoblot, S No No
AGN1S Anti-Glial Nuclear Ab, Type 1 No No
ANN1S Anti-Neuronal Nuclear Ab, Type 1 No No
ANN2S Anti-Neuronal Nuclear Ab, Type 2 No No
ANN3S Anti-Neuronal Nuclear Ab, Type 3 No No
CS2CS CASPR2-IgG CBA, S No No
CRMS CRMP-5-IgG, S No No
DPPCS DPPX Ab CBA, S No No
DPPIS DPPX Ab IFA, S No No
GABCS GABA-B-R Ab CBA, S No No
GFACS GFAP CBA, S No No
GFAIS GFAP IFA, S No No
GRFCS GRAF1 CBA, S No No
GRFIS GRAF1 IFA, S No No
IGG_A IgG Asialo. GM1 No No
IGG_D IgG Disialo. GD1b No No
IG5CS IgLON5 CBA, S No No
IG5IS IgLON5 IFA, S No No
IGM_A IgM Asialo. GM1 No No
IGM_D IgM Disialo. GD1b No No
IGM_M IgM Monos. GM1 No No
ITPCS ITPR1 CBA, S No No
ITPIS ITPR1 IFA, S No No
LG1CS LGI1-IgG CBA, S No No
GL1CS mGluR1 Ab CBA, S No No
GL1IS mGluR1 Ab IFA, S No No
NIFIS NIF IFA, S No No
NFLCS NIF Light Chain CBA, S No No
NMDCS NMDA-R Ab CBA, S No No
CCPQ P/Q-Type Calcium Channel Ab No No
PC1BS PCA-1 Immunoblot, S No No
PCTBS PCA-Tr Immunoblot, S No No
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No No
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No No
SRPIS SRP IFA Screen, S No No
SRPBS SRP Immunoblot, S No No
AMPHS Amphiphysin Ab, S No No
APBCS AP3B2 CBA, S No No
APBIS AP3B2 IFA, S No No
NCDCS Neurochondrin CBA, S No No
NCDIS Neurochondrin IFA, S No No
NFHCS NIF Heavy Chain CBA, S No No
SP5CS Septin-5 CBA, S No No
SP5IS Septin-5 IFA, S No No
SP7CS Septin-7 CBA, S No No
SP7IS Septin-7 IFA, S No No
PDEIS PDE10A Ab IFA, S No No
T46CS TRIM46 Ab CBA, S No No
T46IS TRIM46 Ab IFA, S No No

Report Available

Varies

Day(s) Performed

Varies

Clinical Reference

1. Lancaster E, Martinez-Hernandez E, Dalmau J. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. Neurology. 2011;77(2):179-189

2. Horta ES, Lennon VA, Lachance DH, et al. Neural autoantibody clusters aid diagnosis of cancer. Clin Cancer Res. 2014;20(14):3862-3869

3. Gilligan M, McGuigan C, McKeon. A.paraneoplastic neurologic disorders. Curr Neurol Neurosci Rep. 2023;23(3):67-82. doi:10.1007/s11910-023-01250-w

4. Graus F, Vogrig A, Muniz-Castrillo S, et al. Updated diagnostic criteria for paraneoplastic neurologic syndromes. Neurol Neuroimmunol Neuroinflamm. 2021;8(4):e1014

Method Name

AGN1S, AMPHS, ANN1S, ANN2S, ANN3S, CRMS, DPPIS, GL1IS, PCAB2, PCABP, PCATR, GRFIS, IG5IS, ITPIS, GFAIS, SRPIS, NIFIS, APBIS, NCDIS, SP5IS, SP7IS, PDEIS, T46IS: Indirect Immunofluorescence Assay (IFA)

AMPCS, CS2CS, DPPCS, GABCS, GL1CS, LG1CS, NMDCS, GRFCS, IG5CS, ITPCS, GFACS, NFLCS, NFHCS, AINCS, APBCS, NCDCS, SP5CS, SP7CS, T46CS: Cell Binding Assay (CBA)

CCPQ, GANG: Radioimmunoassay (RIA)

ACMFS: Flow Cytometry (FACS)

IGG_A, IGG_D, IGM_A, IGM_D, IGM_M: Enzyme-linked Immunosorbent Assay (EIA)

AGNBS, AMIBS, AN1BS, AN2BS, PC1BS, PCTBS, SRPBS: Immunoblot (IB)

Specimen Type

Serum


Ordering Guidance


This test is only appropriate for follow-up in patients who have previously tested positive in a serum test. If patients have not previously been positive in a serum test, order one of the following:

 

-AIAES / Axonal Neuropathy, Autoimmune/Paraneoplastic Evaluation, Serum

-CDS1 / CNS Demyelinating Disease Evaluation, Serum

-CIDP / Chronic Inflammatory Demyelinating Polyradiculoneuropathy/Nodopathy Eval, Serum

-DYS2 / Dysautonomia, Autoimmune/Paraneoplastic Evaluation, Serum

-DMS2 / Dementia, Autoimmune/Paraneoplastic Evaluation, Serum

-ENS2 / Encephalopathy, Autoimmune/Paraneoplastic Evaluation, Serum

-EPS2 / Epilepsy, Autoimmune/Paraneoplastic Evaluation, Serum

-GID2 / Gastrointestinal Dysmotility, Autoimmune/Paraneoplastic Evaluation, Serum

-MAS1 / Myelopathy, Autoimmune/Paraneoplastic Evaluation, Serum

-MDS2 / Movement Disorder, Autoimmune/Paraneoplastic Evaluation, Serum

-MGLE / Myasthenia Gravis/Lambert-Eaton Myasthenic Syndrome Evaluation, Serum

-MGMR / Myasthenia Gravis Evaluation with Muscle-Specific Kinase (MuSK) Reflex, Serum

-NMS1 / Necrotizing Myopathy Evaluation, Serum

-PCDES / Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Serum

-SPPS / Stiff-Person Spectrum Disorders/PERM Evaluation, Serum

 

This test should not be requested in 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.



Specimen Required


Collection Container/Tube:

Preferred:Red top

Acceptable:Serum gel

Submission Container/Tube: 13 x 75-mm plastic screw-top vial

Specimen Volume: 4 mL

Collection Instructions: Centrifuge within 2 hours. Aliquot and ship in 13 x 75-mm plastic screw-top vial.


Specimen Minimum Volume

2 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 28 days
  Frozen  28 days
  Ambient  72 hours

Reference Values

Test ID

Reporting Name

Methodology*

Reference Value

GANG

AChR Ganglionic Neuronal Ab, S

RIA

≤0.02 nmol/L

ACMFS

AChR Modulating Flow Cytometry, S

FACS

Negative

AGNBS

AGNA-1 Immunoblot, S

IB

Negative

AINCS

Alpha Internexin CBA, S

CBA

Negative

AMPCS

AMPA-R Ab CBA, S

CBA

Negative

AMPHS

Amphiphysin Ab, S

IFA

Negative

AMIBS

Amphiphysin Immunoblot, S

IB

Negative

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

Negative

ANN1S

Anti-Neuronal Nuclear Ab, Type 1

IFA

Negative

ANN2S

Anti-Neuronal Nuclear Ab, Type 2

IFA

Negative

ANN3S

Anti-Neuronal Nuclear Ab, Type 3

IFA

Negative

APBCS

AP3B2 CBA, S

CBA

Negative

APBIS

AP3B2 IFA, S

IFA

Negative

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

CRMS

CRMP-5-IgG, S

IFA

Negative

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPIS

DPPX Ab IFA, S

IFA

Negative

GABCS

GABA-B-R Ab CBA, S

CBA

Negative

GFACS

GFAP CBA, S

CBA

Negative

GFAIS

GFAP IFA, S

IFA

Negative

GRFCS

GRAF1 CBA, S

CBA

Negative

GRFIS

GRAF1 IFA, S

IFA

Negative

IGG_A

IgG Asialo. GM1

EIA

Negative

IGG_D

IgG Disialo. GD1b

EIA

Negative

IG5CS

IgLON5 CBA, S

CBA

Negative

IG5IS

IgLON5 IFA, S

IFA

Negative

IGM_A

IgM Asialo. GM1

EIA

Negative

IGM_D

IgM Disialo. GD1b

EIA

Negative

IGM_M

IgM Monos. GM1

EIA

Negative

ITPCS

ITPR1 CBA, S

CBA

Negative

ITPIS

ITPR1 IFA, S

IFA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

NCDCS

Neurochondrin CBA, S

CBA

Negative

NCDIS

Neurochondrin IFA, S

IFA

Negative

NFHCS

NIF Heavy Chain CBA, S

CBA

Negative

NIFIS

NIF IFA, S

IFA

Negative

NFLCS

NIF Light Chain CBA, S

CBA

Negative

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

CCPQ

P/Q-Type Calcium Channel Ab

RIA

≤0.02 nmol/L

PC1BS

PCA-1 Immunoblot, S

IB

Negative

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

PCABP

Purkinje Cell Cytoplasmic Ab Type 1

IFA

Negative

PCAB2

Purkinje Cell Cytoplasmic Ab Type 2

IFA

Negative

PCATR

Purkinje Cell Cytoplasmic Ab Type Tr

IFA

Negative

SP5CS

Septin-5 CBA, S

CBA

Negative

SP5IS

Septin-5 IFA, S

IFA

Negative

SP7CS

Septin-7 CBA, S

CBA

Negative

SP7IS

Septin-7 IFA, S

IFA

Negative

SRPIS

SRP IFA Screen, S

IFA

Negative

SRPBS

SRP Immunoblot, S

IB

Negative

PDEIS

PDE10A Ab IFA, S

IFA

Negative

T46CS

TRIM46 Ab CBA, S

CBA

Negative

T46IS

TRIM46 Ab IFA, S

IFA

Negative

 

*Methodology abbreviations:

CBA: Cell-binding assay

FACS: Flow Cytometry

IB: Immunoblot

IFA: Immunofluorescence assay

RIA: Radioimmunoassay

WB: Western blot (WB)

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

83519 GANG (if appropriate)

86043 ACMFS (if appropriate)

84182 AGNBS (if appropriate)

86255 AINCS (if appropriate)

86255 AMPCS (if appropriate)

86255 AMPHS (if appropriate)

84182 AMIBS (if appropriate)

84182 AN1BS (if appropriate)

84182 AN2BS (if appropriate)

86255 AGN1S (if appropriate)

86255 ANN1S (if appropriate)

86255 ANN2S (if appropriate)

86255 ANN3S (if appropriate)

86255 APBCS (if appropriate)

86255 APBIS (if appropriate)

86255 CS2CS (if appropriate)

86255 CRMS (if appropriate)

86255 DPPCS (if appropriate)

86255 DPPIS (if appropriate)

86255 GABCS (if appropriate)

86255 GFACS (if appropriate)

86255 GFAIS (if appropriate)

86255 GRFCS (if appropriate)

86255 GRFIS (if appropriate)

83516 IGG_A (if appropriate)

83516 IGG_D (if appropriate)

86255 IG5CS (if appropriate)

86255 IG5IS (if appropriate)

83516 IGM_A (if appropriate)

83516 IGM_D (if appropriate)

83516 IGM_M (if appropriate)

86255 ITPCS (if appropriate)

86255 ITPIS (if appropriate)

86255 LG1CS (if appropriate)

86255 GL1CS (if appropriate)

86255 GL1IS (if appropriate)

86255 NCDCS (if appropriate)

86255 NCDIS (if appropriate)

86255 NFHCS (if appropriate)

86255 NIFIS (if appropriate)

86255 NFLCS (if appropriate)

86255 NMDCS (if appropriate)

83519 CCPQ (if appropriate)

84182 PC1BS (if appropriate)

84182 PCTBS (if appropriate)

86255 PCABP (if appropriate)

86255 PCAB2 (if appropriate)

86255 PCATR (if appropriate)

86255 PDEIS (if appropriate)

86255 SP5CS (if appropriate)

86255 SP5IS (if appropriate)

86255 SP7CS (if appropriate)

86255 SP7IS (if appropriate)

86255 SRPIS (if appropriate)

84182 SRPBS (if appropriate)

86255 T46CS (if appropriate)

86255 T46IS (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PNEFS Neuroimmunology Ab Follow-up, S 80615-8

 

Result ID Test Result Name Result LOINC Value
84300 Neuroimmunology Ab Follow-up, S 80615-8

Forms

If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Mayo Clinic Laboratories | Endocrinology Catalog Additional Information:

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