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Test Code LAB4416/1295/MISC Pediatric Autoimmune Encephalopathy/CNS Disorder Evaluation, Serum

Important Note

This test does NOT have a unique ordering code. Include the following information in a comment to indicate the specific test you need: 

Peds ACNS, Serum - Mayo (PCDES)

Additional Codes

Mayo Code: PCDES


Ordering Guidance


Multiple neuroimmunology profile tests are available. For testing that is performed with each profile, see Autoimmune Neurology Antibody Matrix.



Necessary Information


Provide the following information:

-Relevant clinical information

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



Specimen Required


Patient Preparation:

1. For optimal antibody detection, specimen collection is recommended prior to initiation of immunosuppressant medication or intravenous immunoglobulin treatment.

2. 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.

 

Collection Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Submission Container/Tube: Plastic vial

Specimen Volume: 4 mL


Method Name

AMPCS, CS2CS, DPPCS, GABCS, GFACS, GL1CS, LG1CS, NMDCS: Cell-Binding Assay (CBA)

 

MOGFS, MOGTS, NMOFS, NMOTS: Flow Cytometry

 

AMPHS, AGN1S, AMPIS, ANN1S, ANN2S, ANN3S, DPPIS, DPPTS, GFAIS, GFATS, GL1IS, GL1TS, NMDIS, PCAB2, PCABP, PCATR: Indirect Immunofluorescence (IFA)

 

GD65S: Radioimmunoassay (RIA)

 

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

Reporting Name

Peds Autoimm Enceph CNS, S

Specimen Type

Serum

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Day(s) Performed

Profile tests: Monday through Sunday; Reflex tests: Varies

Report Available

10 to 13 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. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

86341

86255 x 11

LOINC Code Information

Test ID Test Order Name Order LOINC Value
PCDES Peds Autoimm Enceph CNS, S In Process

 

Result ID Test Result Name Result LOINC Value
61516 NMDA-R Ab CBA, S 93503-1
61519 GABA-B-R Ab CBA, S 93428-1
605131 Peds Autoimmune CNS Interp, S 69048-7
80150 ANNA-1, S 94342-3
81596 GAD65 Ab Assay, S 94345-6
83076 PCA-Tr, S 94352-2
38324 NMO/AQP4 FACS, S 43638-6
64279 LGI1-IgG CBA, S 94287-0
64281 CASPR2-IgG CBA, S 94285-4
65563 MOG FACS, S 90248-6
64930 DPPX Ab IFA, S 82976-2
64928 mGluR1 Ab IFA, S 94347-2
605155 GFAP IFA, S 94346-4
36349 Reflex Added 77202-0

Secondary ID

605129

Useful For

Evaluating children with autoimmune central nervous system disorders using serum specimens

Clinical Information

Autoimmune encephalitis and myelitis is increasingly recognized as a cause of central nervous system disease in children and adolescents. N-methyl-D-aspartate receptor antibody (NMDA-R) encephalitis and myelin oligodendrocyte glycoprotein (MOG) autoimmunity are most common, though other entities, including aquaporin-4 autoimmunity, contactin-associated protein-like 2 (CASPR2) autoimmunity, autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy, and paraneoplastic encephalomyelopathies, may also occur in children.

Interpretation

This profile is consistent with an autoimmune central nervous system disorder.

Cautions

Negative results do not exclude a diagnosis of an autoimmune central nervous system disorder.

 

Intravenous immunoglobulin (IVIg) treatment prior to the serum collection may cause a false-positive result.

Clinical Reference

1. Dubey D, Pittock SJ, Krecke KN, et al: Clinical, radiologic, and prognostic features of myelitis associated with myelin oligodendrocyte glycoprotein autoantibody. JAMA Neurol. 2019 Mar 1;76(3):301-309. doi: 10.1001/jamaneurol.2018.4053

2. McKeon A, Lennon VA, Lotze T, et al: CNS aquaporin-4 autoimmunity in children. Neurology. 2008 Jul 8;71(2):93-100

3. Dubey D, Hinson SR, Jolliffe EA, et al: Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year. J Neuroimmunol. 2018 Aug 15;321:157-163. doi: 10.1016/j.jneuroim.2018.04.016

4. Philipps G, Alisanski SB, Pranzatelli M, Clardy SL, Lennon VA, McKeon A: Purkinje cell cytoplasmic antibody type 1 (anti-Yo) autoimmunity in a child with Down syndrome. JAMA Neurol. 2014 Mar;71(3):347-349

5. Lopez-Chiriboga AS, Klein C, Zekeridou A, et al: LGI1 and CASPR2 neurological autoimmunity in children. Ann Neurol. 2018 Sep;84(3):473-480. doi: 10.1002/ana.25310

6. Lopez-Chiriboga AS, Majed M, Fryer J, et al: Association of MOG-IgG serostatus with relapse after acute disseminated encephalomyelitis and proposed diagnostic criteria for MOG-IgG-associated disorders. JAMA Neurol. 2018 Nov 1;75(11):1355-1363. doi: 10.1001/jamaneurol.2018.1814

7. Clardy SL, Lennon VA, Dalmau J: Childhood onset of stiff-man syndrome. JAMA Neurol. 2013 Dec;70(12):1531-1536. doi: 10.1001/jamaneurol.2013.4442

8. Banwell B, Tenembaum S, Lennon VA, et al: Neuromyelitis optica-IgG in childhood inflammatory demyelinating CNS disorders. Neurology. 2008 Jan 29;70(5):344-352. doi: 10.1212/01.wnl.0000284600.80782.d5

Method Description

Indirect Immunofluorescence Assay:

Before testing, patient's serum is preabsorbed with liver powder to remove nonorgan-specific autoantibodies. After applying to a composite substrate of frozen mouse tissues (brain, kidney, and gut) and washing, fluorescein-conjugated goat-antihuman IgG is applied to detect the distribution and pattern of patient IgG binding.(Pittock SJ, Kryzer TJ, Lennon VA: Paraneoplastic antibodies coexist and predict cancer, not neurological syndrome. Ann Neurol. 2004;56:715-719; Basal E, Zalewski N, Kryzer TJ, et al: Paraneoplastic neuronal intermediate filament autoimmunity. Neurology. 2018 Oct 30;91[18]:e1677-e1689)

 

Radioimmunoassay:

Goat-antihuman IgG and IgM is used as precipitant in all assays. Cation channel protein antigens are solubilized from neuronal or muscle membrane, in nonionic detergent, and complexed with a selective high-affinity ligand labeled with (125)I. (125)I-labelled recombinant human glutamic acid decarboxylase-65 (GAD65) antigen is used to confirm GAD65 autoantibody (when suspected from immunofluorescent staining pattern).(Griesmann GE, Kryzer TJ, Lennon VA: Autoantibody profiles of myasthenia gravis and Lambert-Eaton myasthenic syndrome. In: Rose NR, Hamilton RG, et al. eds. Manual of Clinical and Laboratory Immunology. 6th ed. ASM Press; 2002:1005-1012; Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid decarboxylase [GAD65] autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc. 1998;73[12]:1161-1166; Jones AL, Flanagan EP, Pittock SJ, et al: Responses to and outcomes of treatment of autoimmune cerebellar ataxia in adults. JAMA Neurol. 2015 Nov;72[11]:1304-1312. doi: 10.1001/jamaneurol.2015.2378)

 

Immunoblot:

All steps are performed at ambient temperature (18-28° C) utilizing the EUROBlot One instrument. 

Diluted patient serum (1:101) is added to test strips (strips containing recombinant antigen manufactured and purified using biochemical methods) in individual channels and incubated for 30 minutes. Positive serums will bind to the purified recombinant antigen and negative serums will not bind. Strips are washed to remove unbound antibodies and then incubated with antihuman IgG antibodies (alkaline phosphatase-labeled) and incubated for 30 minutes. The strips are again washed to remove unbound antihuman IgG antibodies and nitroblue tetrazolium chloride/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) substrate is added. Alkaline phosphatase enzyme converts the soluble substrate into a colored insoluble product on the membrane to produce 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)

 

Cell-Binding Assay:

Patient serum 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)

 

Fluorescence-Activated Cell Sorting Assay:

Human embryonic kidney cells (HEK 293) are transfected transiently with a plasmid (pIRES2- Aequorea coerulescens green fluorescent protein [AcGFP]) encoding both green fluorescent protein (AcGFP) and AQP4-M1. After 36 hours, a mixed population of cells (transfected expressing AQP4 or MOG on the surface and AcGFP in the cytoplasm and nontransfected lacking AQP4 or MOG and AcGFP) are lifted and resuspended in live cell-binding buffer. Cells are incubated with patient serum and an AlexaFluor 647-labeled secondary antibody is added. Two populations are gated on the basis of AcGFP expression: positive (high AQP4 or MOG expression) and negative (low or no AQP4 or MOG expression). Positivity is based on the ratio (Positive >2.0) of the average median fluorescence intensity (MFI) of each cell population (MFI GFP positive:MFI GFP negative).(Unpublished Mayo method)

Specimen Retention Time

28 days

Specimen Minimum Volume

2 mL

Reference Values

Test ID

Reporting name

Methodology*

Reference value

PCSI

Peds Autoimmune CNS Interp, S

Medical interpretation

NA

ANN1S

ANNA-1, S

IFA

<1:240**

CS2CS

CASPR2-IgG CBA, S

CBA

Negative

DPPIS

DPPX Ab IFA, S

IFA

Negative

GABCS

GABA-B-R Ab CBA, S

CBA

Negative

GD65S

GAD65 Ab Assay, S

RIA

≤0.02 nmol/L

Reference values apply to all ages.

GFAIS

GFAP IFA, S

IFA

Negative

LG1CS

LGI1-IgG CBA, S

CBA

Negative

GL1IS

mGluR1 Ab IFA, S

IFA

Negative

MOGFS

MOG FACS, S

FACS

Negative

NMDCS

NMDA-R Ab CBA, S

CBA

Negative

NMOFS

NMO/AQP4 FACS, S

FACS

Negative

PCATR

PCA-Tr, S

IFA

<1:240**

Reflex Information:

Test ID

Reporting name

Methodology

Reference value

AGN1S

Anti-Glial Nuclear Ab, Type 1

IFA

<1:240

AGNBS

AGNA-1 Immunoblot, S

IB

Negative

AMIBS

Amphiphysin Immunoblot, s

IB

Negative

AMPCS

AMPA-R Ab CBA, S

CBA

Negative

AMPHS

Amphiphysin Ab, S

IFA

<1:240

AMPIS

AMPA-R Ab IF Titer Assay, S

IFA

<1:120

AN1BS

ANNA-1 Immunoblot, S

IB

Negative

AN2BS

ANNA-2 Immunoblot, S

IB

Negative

ANN2S

ANNA-2, S

IFA

<1:240**

ANN3S

ANNA-3, S

IFA

<1:240

DPPCS

DPPX Ab CBA, S

CBA

Negative

DPPTS

DPPX Ab IFA Titer, S

IFA

<1:240

GFACS

GFAP CBA, S

CBA

Negative

GFATS

GFAP IFA Titer, S

IFA

<1:240

GL1CS

mGluR1 Ab CBA, S

CBA

Negative

GL1TS

mGluR1 Ab IFA Titer, S

IFA

<1:240

MOGTS

MOG FACS Titer, S

FACS

<1:20

NMDIS

NMDA-R Ab IF Titer Assay, S

IFA

<1:120

NMOTS

NMO/AQP4 FACS Titer, S

FACS

<1:5

PC1BS

PCA-1 Immunoblot, S

IB

Negative

PCAB2

PCA-2, S

IFA

<1:240**

PCABP

PCA-1, S

IFA

<1:240**

PCTBS

PCA-Tr Immunoblot, S

IB

Negative

 

*Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Fluorescence activated cell sorting assay (FACS)

Radioimmunoassay (RIA)

Immunoblot (IB)

 

**Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include non-neuronal elements may be reported as "uninterpretable."

Specimen Stability Information

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

Profile Information

Test ID Reporting Name Available Separately Always Performed
PCSI Peds Autoimmune CNS Interp, S No Yes
ANN1S Anti-Neuronal Nuclear Ab, Type 1 No Yes
CS2CS CASPR2-IgG CBA, S No Yes
DPPIS DPPX Ab IFA, S No Yes
GABCS GABA-B-R Ab CBA, S No Yes
GD65S GAD65 Ab Assay, S Yes Yes
GFAIS GFAP IFA, S No Yes
LG1CS LGI1-IgG CBA, S No Yes
GL1IS mGluR1 Ab IFA, S No Yes
MOGFS MOG FACS, S Yes Yes
NMDCS NMDA-R Ab CBA, S No Yes
NMOFS NMO/AQP4 FACS, S Yes Yes
PCATR Purkinje Cell Cytoplasmic Ab Type Tr No Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
AGN1S Anti-Glial Nuclear Ab, Type 1 No No
AGNBS AGNA-1 Immunoblot, S No No
AMIBS Amphiphysin Immunoblot, S No No
AMPCS AMPA-R Ab CBA, S No No
AMPHS Amphiphysin Ab, S No No
AMPIS AMPA-R Ab IF Titer Assay, S No No
AN1BS ANNA-1 Immunoblot, S No No
AN2BS ANNA-2 Immunoblot, S No No
ANN2S Anti-Neuronal Nuclear Ab, Type 2 No No
ANN3S Anti-Neuronal Nuclear Ab, Type 3 No No
DPPCS DPPX Ab CBA, S No No
DPPTS DPPX Ab IFA Titer, S No No
GFACS GFAP CBA, S No No
GFATS GFAP IFA Titer, S No No
GL1CS mGluR1 Ab CBA, S No No
GL1TS mGluR1 Ab IFA Titer, S No No
MOGTS MOG FACS Titer, S No No
NMDIS NMDA-R Ab IF Titer Assay, S No No
NMOTS NMO/AQP4 FACS Titer, S No No
PC1BS PCA-1 Immunoblot, S No No
PCAB2 Purkinje Cell Cytoplasmic Ab Type 2 No No
PCABP Purkinje Cell Cytoplasmic Ab Type 1 No No
PCTBS PCA-Tr Immunoblot, S No No

Testing Algorithm

If indirect immunofluorescence assay (IFA) patterns suggest antineuronal nuclear antibodies (ANNA)-1, then ANNA-1 immunoblot and ANNA-2 immunoblot are performed at an additional charge.

 

If IFA patterns suggest ANNA-2 antibody, then ANNA-2 immunoblot, ANNA-1 immunoblot, and ANNA-2 antibody IFA are performed at an additional charge.

 

If IFA patterns suggest ANNA-3 antibody, then ANNA-3 IFA is performed at an additional charge.

 

If IFA patterns suggest Purkinje cytoplasmic antibody (PCA)-1 antibody, then PCA-1 immunoblot and PCA-1 IFA are performed at an additional charge.

 

If IFA patterns suggest PCA-2 antibody, then PCA-2 IFA is performed at an additional charge.

 

If IFA patterns suggest PCA-Tr antibody, then PCA-Tr immunoblot is performed at an additional charge.

 

If IFA patterns suggest amphiphysin antibody, then amphiphysin immunoblot and amphiphysin antibody IFA titer are performed at an additional charge.

 

If IFA pattern suggests N-methyl-D-aspartate receptor (NMDA-R) antibody, then NMDA-R IFA titer is performed at an additional charge.

 

If IFA pattern suggests alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPA-R) antibody, then AMPA-R antibody cell-binding assay (CBA) and AMPA-R IFA titer are performed at an additional charge.

 

If IFA pattern suggests gamma-aminobutyric acid B receptor (GABA-B-R) antibody, then GABA-B-R IFA titer is performed at an additional charge.

 

If IFA pattern suggests dipeptidyl-peptidase-like protein-6 (DPPX) antibody, then DPPX antibody CBA and DPPX IFA titer are performed at an additional charge.

 

If IFA pattern suggests metabotropic glutamate receptor 1 (mGluR1) antibody, then mGluR1antibody CBA and mGluR1 IFA titer are performed at an additional charge.

 

If IFA pattern suggests glial fibrillary acidic protein (GFAP) antibody, then GFAP antibody CBA and GFAP IFA titer are performed at an additional charge.

 

If neuromyelitis optica/aquaporin-4-IgG (NMO/AQP4-IgG) fluorescence-activated cell sorting (FACS) screen assay requires further investigation, then NMO/AQP4-IgG FACS titration assay is performed at an additional charge.

 

If myelin oligodendrocyte glycoprotein (MOG) FACS screen assay requires further investigation, then MOG FACS titration assay is performed at an additional charge.

 

For more information, see the following:

Pediatric Autoimmune Encephalopathy Central Nervous System Disorders Evaluation Algorithm-Serum

Pediatric Autoimmune Central Nervous System Demyelinating Disease Diagnostic Algorithm