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.
A thorough understanding of a patient’s history, along with clinical examination and laboratory testing, are needed for a clinico-sero-pathological diagnosis of immune-mediated necrotizing myopathy (IMNM). To assess the probability of your patient having IMNM, see the Immune-mediated necrotizing myopathy calculator.
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 the indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, then the SRP IFA titer and SRP54 immunoblot will be performed at an additional charge.
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.
Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test
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.
A thorough understanding of a patient’s history, along with clinical examination and laboratory testing, are needed for a clinico-sero-pathological diagnosis of immune-mediated necrotizing myopathy (IMNM). To assess the probability of your patient having IMNM, see the Immune-mediated necrotizing myopathy calculator.
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 the indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, then the SRP IFA titer and SRP54 immunoblot will be performed at an additional charge.
Specimen Type
Describes the specimen type validated for testing
Serum
Ordering Guidance
Before ordering this test, assess the probability of the patient having immune-mediated necrotizing myopathy by using the Immune-mediated necrotizing myopathy calculator.
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
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 3 mL
Collection Instructions: Centrifuge within 2 hours of collection and aliquot serum into a plastic vial.
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. The minimum volume is sufficient for one attempt at testing.
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 | |
| Ambient | 72 hours | ||
| Frozen | 28 days |
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.
A thorough understanding of a patient’s history, along with clinical examination and laboratory testing, are needed for a clinico-sero-pathological diagnosis of immune-mediated necrotizing myopathy (IMNM). To assess the probability of your patient having IMNM, see the Immune-mediated necrotizing myopathy calculator.
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 the indirect immunofluorescence assay (IFA) pattern suggests signal recognition particle (SRP) antibody, then the SRP IFA titer and SRP54 immunoblot will be performed at an additional charge.
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
Method Description
Describes how the test is performed and provides a method-specific reference
Signal Recognition Protein Indirect Immunofluorescence Assay:
The patient's sample is tested by a standardized indirect immunofluorescence assay (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. Signal recognition protein (SRP)-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Samples that are scored positive are titrated. 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; Version: 03/2018)
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase:
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 from the RLU value obtained for each sample.(Package insert: QUANTA Flash HMGCR 701333. Inova Diagnostics, Inc; 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, which 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; Version: 03/2018)
PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information
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.
Tuesday, Thursday
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.
Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location
Indicates the location of the laboratory that performs the test
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.
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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. It 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.
CPT codes are provided by the performing laboratory.
86255
82397
86256 (if appropriate)
84182 (if appropriate)
LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| NMS1 | Necrotizing Myopathy Evaluation, S | 97561-5 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 603543 | Necrotizing Myopathy Interp, S | 69048-7 |
| 603540 | SRP IFA Screen, S | 97562-3 |
| 607414 | HMG-CoA Reductase Ab, S | 93493-5 |