Test Id : MDC2

If immunofluorescence assay (IFA) pattern suggests amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

If IFA pattern suggests antiglial nuclear antibody (AGNA)-1, then AGNA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, then ANNA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests ANNA-2, then ANNA-2 immunoblot is performed at an additional charge.

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1, then PCA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests PCA-Tr ,then PCA-Tr immunoblot is performed at an additional charge.

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

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

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

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

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

If IFA pattern suggests GTPase regulator associated with focal adhesion kinase-1 (GRAF1) antibody, then GRAF1 CBA and GRAF1 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests IgLON5 antibody, then IgLON5 CBA and IgLON5 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests inositol 1,4,5-trisphosphate receptor (ITPR1) antibody, then ITPR1 CBA and ITPR1 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF antibody IFA titer are performed at an additional charge.

If Kelch-like protein 11 (KLHL11) CBA is reactive, then KLHL11 antibody IFA titer is performed at an additional charge.

See Movement Disorder Autoimmune Evaluation Algorithm-Spinal Fluid

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

Provide the following information:

-Relevant clinical information

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

Patient Preparation:

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

Container/Tube: Sterile vial

Preferred: Vial number 1

Acceptable: Any vial

Specimen Volume: 4 mL

• Movement Disorder Autoimmune Evaluation Algorithm-Spinal Fluid

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

3.5 mL

Evaluating patients with suspected paraneoplastic or other autoimmune movement disorders including patients with ataxia, brainstem encephalitis, chorea, dyskinesias, myoclonus, and parkinsonism using spinal fluid specimens

If immunofluorescence assay (IFA) pattern suggests amphiphysin antibody, then amphiphysin immunoblot is performed at an additional charge.

If IFA pattern suggests antiglial nuclear antibody (AGNA)-1, then AGNA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests antineuronal nuclear antibody (ANNA)-1, then ANNA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests ANNA-2, then ANNA-2 immunoblot is performed at an additional charge.

If IFA pattern suggests Purkinje cytoplasmic antibody (PCA)-1, then PCA-1 immunoblot is performed at an additional charge.

If IFA pattern suggests PCA-Tr ,then PCA-Tr immunoblot is performed at an additional charge.

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

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

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

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

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

If IFA pattern suggests GTPase regulator associated with focal adhesion kinase-1 (GRAF1) antibody, then GRAF1 CBA and GRAF1 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests IgLON5 antibody, then IgLON5 CBA and IgLON5 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests inositol 1,4,5-trisphosphate receptor (ITPR1) antibody, then ITPR1 CBA and ITPR1 antibody IFA titer are performed at an additional charge.

If IFA pattern suggests neuronal intermediate filament (NIF) antibody, then alpha internexin CBA, NIF heavy chain CBA, NIF light chain CBA, and NIF antibody IFA titer are performed at an additional charge.

If Kelch-like protein 11 (KLHL11) CBA is reactive, then KLHL11 antibody IFA titer is performed at an additional charge.

See Movement Disorder Autoimmune Evaluation Algorithm-Spinal Fluid

Autoimmune movement disorders encapsulate a large and diverse group of neurologic disorders occurring either in isolation or accompanying more diffuse autoimmune encephalitic illnesses.

The full range of movement phenomena has been described and, as they often occur in adults, many of the presentations can mimic neurodegenerative disorders, such as autoimmune chorea mimicking Huntington disease. Disorders may be ataxic, hypokinetic (parkinsonism), or hyperkinetic (myoclonus, chorea other dyskinetic disorders). Associated disorders may fall under the rubric of brainstem encephalitis.

The autoantibody targets are diverse and include neuronal surface proteins such as leucine-rich, glioma-inactivated 1 (LGI1), as well as antibodies reactive with intracellular antigens (such as Purkinje cell cytoplasmic antibody-1 [PCA-1]) that are markers of a central nervous system process mediated by CD8+ cytotoxic T cells.

In some instances (such as PCA-1 autoimmunity), antibodies detected in serum and cerebrospinal fluid can be indicative of a paraneoplastic cause and may direct the cancer search. In other instances (such as 65 kDa isoform of glutamic acid decarboxylase [GAD65] autoimmunity), a paraneoplastic cause is very unlikely, and early treatment with immunotherapy may promote improvement or recovery.

Reflex Information:

 *Methodology abbreviations:

Immunofluorescence assay (IFA)

Cell-binding assay (CBA)

Western blot (WB)

Radioimmunoassay (RIA)

Immunoblot (IB)

Neuron-restricted patterns of IgG staining that do not fulfill criteria for ANNA-1, ANNA-2, CRMP-5-IgG, PCA-1, PCA-2, or PCA-Tr may be reported as "unclassified anti-neuronal IgG." Complex patterns that include nonneuronal elements may be reported as "uninterpretable."

A positive antibody result is consistent with a diagnosis of an autoimmune movement disorder.

A search for cancer may be indicated, depending on the antibody profile.

A trial of immune therapy may bring about improvement in neurological symptoms.

A negative antibody test result does not exclude an autoimmune movement disorder.

Corticosteroid treatment prior to the cerebrospinal fluid (CSF) collection may cause a false-negative result.

Intravenous immunoglobulin treatment prior to the CSF collection may cause a false-positive result.

1. Honorat JA, McKeon A: Autoimmune Movement Disorders: a Clinical and Laboratory Approach. Curr Neurol Neurosci Rep. 2017 Jan;17(1):4 doi: 10.1007/s11910-017-0709-2

2. Dubey D, Wilson MR, Clarkson B, et.al:.Expanded clinical phenotype, oncological associations, and immunopathologic insights of paraneoplastic Kelch-like protein-11 encephalitis. JAMA Neurol. 2020 Nov 1;77(11):1420-1429. doi: 10.1001/jamaneurol.2020.2231

• Movement Disorder Autoimmune Evaluation Algorithm-Spinal Fluid

Indirect Immunofluorescence Assay:

The patient's sample is tested by a standardized indirect 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.0000000000000385)

Radioimmunoassay:

Duplicate aliquots of patient specimen are incubated with I(125)-labeled antigen. Immune complexes, formed by adding secondary (goat) antihuman immunoglobulin, are pelleted by centrifugation and washed. Gamma emission from the washed pellet is counted, and mean counts per minute (cpm) are compared with results yielded by high positive and negative control sera. Specimen yielding cpm higher than the background cpm yielded by normal human specimen are retested to confirm positivity and titrated as necessary to obtain a value in the linear range of the assay. The antigen binding capacity (nmol per liter) is calculated from the cpm precipitated at a dilution yielding a linear range value.(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; 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)

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 February;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. doi: 10.1212/WNL.0000000000008472)

Immunoblot:

All steps are performed at room temperature (18-28 degrees C) utilizing the EUROBlot One instrument. Diluted patient specimen (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)

Cell-Binding Assay:

Patient specimen 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)

Methodology for detecting Kelch-like protein 11 (KLHL11)-IgG uses an in-house developed cell binding assay (CBA) with confirmation by tissue immunofluorescence (IFA). The CBA utilizes HEK293 cells that are stably transfected with DNA encoding the KLHL11 protein that has been tagged with green fluorescent protein (GFP). Since KLHL11 is localized to cytoplasmic vesicles when ectopically expressed, cells will be fixed and permeabilized prior to exposure to patient sample. Patients that are positive for KLHL11-IgG will have human IgG bound to the transfected cells. Binding will colocalize with the GFP-tagged KLHL11 protein in cytoplasmic vesicles. Patient IgG will be detected using a tetramethylrhodamine (TRITC)-conjugated anti-human secondary antibody. The negative samples will not bind to KLHL11-GFP in transfected cells. Performed in a 96 well plate format, the plates are scanned, and images saved using the ImageXpress Micro Confocal High-Content Imaging System (Molecular Devices). Images will be scored positive or negative.(Unpublished Mayo method)

Profile tests: Monday through Sunday; Reflex tests: Varies

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• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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.

86255 x19

84182

86341

84182 AGNBC (if appropriate)

86255 AINCC (if appropriate)

86255 AMPCC (if appropriate)

86256 AMPIC (if appropriate)

84182 AMIBC (if appropriate)

84182 AN1BC (if appropriate)

84182 AN2BC (if appropriate)

86255 DPPCC (if appropriate)

86256 DPPTC (if appropriate)

86255 GABCC (if appropriate)

86256 GABIC (if appropriate)

86255 GRFCC (if appropriate)

86256 GRFTC (if appropriate)

86255 IG5CC (if appropriate)

86256 IG5TC (if appropriate)

86255 ITPCC (if appropriate)

86256 ITPTC (if appropriate)

86256-K11TC (if appropriate)

86255 GL1CC (if appropriate)

86256 GL1TC (if appropriate)

86255 NFHCC (if appropriate)

86256 NIFTC (if appropriate)

86255 NFLCC (if appropriate)

86256 NMDIC (if appropriate)

84182 PC1BC (if appropriate)

84182 PCTBC (if appropriate)

Sample Reports

Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports

International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports