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

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

This is a focused algorithmic test 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.

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 U/mL

 

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