Test Catalog

Test Id : NMS1

Necrotizing Myopathy Evaluation, Serum

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

Evaluating patients with suspected necrotizing autoimmune myopathy

Highlights

The utilization of this combinatorial immunoassay provides accuracy and speed in diagnosis of necrotizing autoimmune myopathy (NAM). Early diagnosis facilitates better prognosis through initiation of aggressive immune treatments, typically requiring more than 1 agent, and discontinuation of statin medications. Persons without access to specialty muscle biopsy testing services may be afforded an early diagnosis through application of this testing.

 

Identification of NAM may indicate the presence of a paraneoplastic disorder.

Profile Information
A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.

Test Id Reporting Name Available Separately Always Performed
NSI1 Necrotizing Myopathy Interp, S No Yes
HMGCR HMG-CoA Reductase Ab, S Yes Yes
SRPIS SRP IFA Screen, S No Yes

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
SRPBS SRP Immunoblot, S No No
SRPTS SRP IFA Titer, S No No

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This focused algorithmic test is designed to achieve high sensitivity for identification of antibodies specific for necrotizing autoimmune myopathy (HMGCOA-IgG and SRP-IgG). This test is unique in the market by having an initial screen for signal recognition particle (SRP) antibodies performed using tissue indirect immunofluorescence, which increases clinical sensitivity as compared to SRP immunoblot methodologies.

 

If indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, SRP IFA titer and SRP54 immunoblot are performed at an additional charge.

 

See Necrotizing Myopathy Evaluation in Special Instructions.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Name
A short description of the method used to perform the test

SRPIS, SRPTS: Indirect Immunofluorescence Assay (IFA)

SRPBS: Immunoblot

HMGCR: Chemiluminescent Assay (CIA)

NSI1: Medical Interpretation

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

Necrotizing Myopathy Evaluation, S

Aliases
Lists additional common names for a test, as an aid in searching

Autoimmune myopathy

Necrotizing myopathy

Immune mediated necrotizing myopathy

Statin induced myopathy

HMGCR

SRP 54

SRP

HMG CoA reductase

SRP54

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This focused algorithmic test is designed to achieve high sensitivity for identification of antibodies specific for necrotizing autoimmune myopathy (HMGCOA-IgG and SRP-IgG). This test is unique in the market by having an initial screen for signal recognition particle (SRP) antibodies performed using tissue indirect immunofluorescence, which increases clinical sensitivity as compared to SRP immunoblot methodologies.

 

If indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, SRP IFA titer and SRP54 immunoblot are performed at an additional charge.

 

See Necrotizing Myopathy Evaluation in Special Instructions.

Specimen Type
Describes the specimen type validated for testing

Serum

Necessary Information

Provide the following information:

-Relevant clinical information

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

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 3 mL

Collection Instructions: Centrifuge within 2 hours of collection and aliquot 2 mL into a plastic vial.

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Forms

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

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

2 mL

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

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

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

Evaluating patients with suspected necrotizing autoimmune myopathy

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This focused algorithmic test is designed to achieve high sensitivity for identification of antibodies specific for necrotizing autoimmune myopathy (HMGCOA-IgG and SRP-IgG). This test is unique in the market by having an initial screen for signal recognition particle (SRP) antibodies performed using tissue indirect immunofluorescence, which increases clinical sensitivity as compared to SRP immunoblot methodologies.

 

If indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, SRP IFA titer and SRP54 immunoblot are performed at an additional charge.

 

See Necrotizing Myopathy Evaluation in Special Instructions.

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

Necrotizing autoimmune myopathy (NAM) is a serious, but rare muscle disease strongly associated with autoantibodies to either signal recognition protein (SRP) or 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR).(1) NAM typically manifests with subacute proximal limb muscle weakness and persistently elevated serum creatine kinase (CK) concentrations, but slower onsets can occur and complicate diagnosis. Muscle biopsies in affected patients can demonstrate necrotic and regenerating myofibers without inflammatory infiltrates, suggesting the diagnosis.(2) However, sampling issues and lack of access to persons having expertise in obtaining, preparing, and interpreting muscle biopsy specimens may delay a diagnosis.(3)

 

Early identification of NAM and subsequent aggressive immune-modulating therapy is critical.(1,3) Discovery of SRP- or HMGCR–IgG autoantibodies can aid in establishing an earlier diagnosis and treatment initiation. In addition, the discovery of SRP or HMGCR autoantibodies should prompt a search for an underlying malignancy.(4) Serial testing for these autoantibodies can delay diagnosis with the discovery of either antibody aiding in establishing an earlier diagnosis and treatment initiation.(1,3)

 

The clinical onsets are not specific to NAM consisting of proximal limb weakness in associations with an elevated serum creatinine kinase, with or without exposure to lipid lowering statin medications.(1,3-9) The clinical presentation can be confused with forms of inflammatory (dermatomyositis, polymyositis), toxic, metabolic or even neurodegeneration (ie, muscular dystrophy) and the diagnosis delayed without serological testing by SRP- or HMGCR-autoantibody testing. Panel testing of both HMGCR and SRP autoantibodies is the preferred strategy for the best patient care.

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.

3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase:

<20.0 CU

 

Signal Recognition Particle Antibody Screen:

Negative

 

Signal Recognition Particle Antibody:

Negative

 

Signal Recognition Particle Antibody, Titer:

<1:240

Interpretation
Provides information to assist in interpretation of the test results

Seropositivity for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or signal recognition protein (SRP) autoantibodies supports the clinical diagnosis of necrotizing autoimmune myopathy (NAM). A paraneoplastic basis should be considered, according to age, sex, and other risk factors. In cases of NAM, immune therapy is required and often multiple simultaneously utilized immunotherapies are needed to successfully treat patients.

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

Antibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) or signal recognition protein (SRP) may be detected in cases of polymyositis, dermatomyositis, or other autoimmune disorders. It is recommended that serology results be interpreted along with muscle biopsy findings and in the appropriate clinical context.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Kassardjian CD, Lennon VA, Alfugham NB, et al: Clinical Features and Treatment Outcomes of Necrotizing Autoimmune Myopathy. JAMA Neurol 2015 Sep;72(9):996-1003

2. Emslie-Smith A M, Engel A G: Necrotizing myopathy with pipestem capillaries, microvascular deposition of the complement membrane attack complex (MAC), and minimal cellular infiltration. Neurology 1991;41(6):936-939

3. Ramanathan S, Langguth D, Hardy T, et al: Clinical course and treatment of anti-HMGCR antibody-associated necrotizing autoimmune myopathy. Neurol Neuroimmunol Neuroinflamm 2015 June;2(3):e96

4. Allenbach Y, Keraen J, Bouvier AM, et al: High risk of cancer in autoimmune necrotizing myopathies: usefulness of myositis specific antibody. Brain 2016 Aug;139(Pt 8):2131-2135

5. Christopher-Stine L, Casciola-Rosen L, Hong G, et al: A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum 2010 May;62(9):2757-2766

6. Mammen AL, Chung T, Christopher-Stine L, et al: Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum 2011 Mar;63(3):713-721

7. Hengstman GJ, ter Laak HJ, Vree Egberts WT, et al: Anti-signal recognition particle autoantibodies: marker of a necrotising myopathy. Ann Rheum Dis 2006;65(12):1635-1638

8. Miller T, Al-Lozi MT, Lopate G, Pestronk A: Myopathy with antibodies to the signal recognition particle: clinical and pathological features. J Neurol Neurosurg Psychiatry 2002 Oct;73(4):420-428

9. Watanabe Y, Uruha A, Suzuki S, et al: Clinical features and prognosis in anti-SRP and anti-HMGCR necrotising myopathy. J Neurol Neurosurg Psychiatry 2016 Oct;87(10):1038-1044

Special Instructions
Library of PDFs including pertinent information and forms related to the test

Method Description
Describes how the test is performed and provides a method-specific reference

Signal recognition protein (SRP) Indirect Immunofluorescence Assay (IFA):

The patient’s sample is tested by a standardized IFA that uses composite frozen sections of mouse cerebellum, kidney, and gut tissues. After incubation with patient sample and washing, fluorescein-conjugated goat antihuman IgG is applied. SRP-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Samples that are scored positive are titrated to an endpoint. Interference by coexisting non-neuron-specific autoantibodies is eliminated or lessened by serologic absorption. This method does not distinguish between antibodies against different SRP proteins.(Package insert: EUROLINE Autoimmune Inflammatory Myopathies 16 Ag (IgG) test instruction. EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany. Version: 20/03/2018)

 

HMGCR CIA:

IgG antibodies to 3-Hydroxy-3- Methylglutaryl Coenzyme A reductase (HMGCR) are detected by a chemiluminescent assay using the Inova BIO-FLASH instrument. HMGCR antigen is coated on to paramagnetic beads, which are stored in the reagent cartridge lyophilized. When the assay cartridge is ready to be used for the first time, a buffer solution is added to the tube containing the beads, and the beads are resuspended with the buffer. The reagent cartridge is then loaded onto the BIO-FLASH instrument. A patient serum sample is diluted 1:17 by the instrument in a disposable plastic cuvette. An aliquot of the diluted patient serum, HMGCR-coupled beads, and assay buffer are combined into a second cuvette, and mixed. This cuvette is incubated at 37 degrees C. The beads are then magnetized and washed several times. Isoluminol conjugated anti-human IgG antibody is then added to the cuvette, and incubated at 37 degrees C. Again, the beads are magnetized and washed repeatedly. The isoluminol conjugate produces a luminescent reaction when "Trigger" reagents are added to the cuvette. The light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. RLU values are proportional to the amount of bound isoluminol conjugate, which in turn is proportional to the amount of anti-HMGCR antibodies bound to the antigen on the beads. The QUANTA Flash HMGCR assay utilizes a predefined lot specific Master Curve that is uploaded into the instrument through the reagent cartridge barcode. Based on the results obtained by running two calibrators, an instrument specific Working Curve is created, which is used by the software to calculate chemiluminescent units (CU) from the RLU value obtained for each sample.(Package insert: QUANTA Flash HMGCR 701333 Inova Diagnostics, Inc, San Diego ,CA) v04, 09/2018

 

SRP Immunoblot:

The assay is performed using the EUROBlotOne instrument. All reagents required are supplied in the kit. Samples are diluted 1:100 (15 mcL in 1.5 mL sample buffer) and added to the strips placed in incubation trays. The sample and test strips are incubated for 30 minutes at room temperature. Unbound antibodies are removed from trays by washing steps using wash buffer. Bound patient IgG antibodies are detected by adding antihuman-IgG antibodies coupled to horse radish peroxidase followed by incubation at room temperature for 30 minutes. The strips are washed again to remove excess antihuman-IgG antibodies. The substrate is added for 10 minutes (room temperature) and the reaction is subsequently stopped. The strip is scanned and band intensities are digitized. The digital image is converted to band signal intensities by the EUROLineScan software and these are normalized to an internal standard. Bands corresponding to SRP with signal intensities of 15 U (arbitrary) or greater are reported as positive. The SRP antigen used is recombinant SRP 54. Positive immunoblot results confirm that a patient’s serum contains antibodies directed against the SRP 54 subunit. Negative immunoblot results do exclude the presence of SRP antibodies.(Package insert: EUROLINE Autoimmune Inflammatory Myopathies 16 Ag (IgG) test instruction. EUROIMMUN Medizinische Labordiagnostika AG, Lübeck, Germany. Version: 20/03/2018)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Signal Recognition Particle Antibody:

Tuesday, Thursday

 

Signal Recognition Particle Antibody Screen:

Tuesday, Thursday, Sunday

 

Signal Recognition Particle Antibody, Titer:

Tuesday, Thursday, Sunday

 

3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase:

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

10 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

28 days

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • 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.

Test Classification
Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

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
Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

86255

82397

86256 (if appropriate)

84182 (if appropriate)

LOINC® Information

Test Id Test Order Name Order LOINC Value
NMS1 Necrotizing Myopathy Evaluation, S 97561-5
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Pdf

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