Sign in →

Epic Code LAB848 3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase, Serum

Additional Codes

Mayo Code: HMGCR

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful For

Evaluating patients with suspected necrotizing autoimmune myopathy

 

Measuring 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies

Specimen Type

Serum


Ordering Guidance


NMS1 / Necrotizing Myopathy Evaluation, Serum is the preferred first tier test for identification of antibodies specific for necrotizing autoimmune myopathy (HMGCOA-IgG and SRP-IgG). This initial evaluation includes signal recognition particle (SRP) antibodies performed using tissue indirect immunofluorescence, which increases the clinical sensitivity as compared to SRP immunoblot methodologies.



Specimen Required


Container/Tube:

Preferred: Red top

Acceptable: Serum gel

Specimen Volume: 2 mL


Laboratory Test Directory Note:

COLLECTION NOTE: Volumes listed are in serum or plasma, draw approximately 2 1/2 times the requested volume in whole blood.

Specimen Minimum Volume

1 mL

Specimen Stability Information

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

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject

Cautions

Negative results do not exclude the diagnosis of necrotizing autoimmune myopathy (NAM). Only approximately 35% of cases of NAM are associated with autoantibodies against 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). The remainder of cases are either positive for signal recognition protein (SRP) autoantibodies (approximately 20%-30%) or are seronegative (approximately 35%).

 

Very rarely HMGCR antibodies can be detected in diseases other than NAM. A muscle biopsy is recommended.

Clinical Information

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 association 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.

Method Name

Chemiluminescence Immunoassay (CIA)

Report Available

2 days

Reporting Name

HMG-CoA Reductase Ab, S

Reference Values

<20.0 CU

Interpretation

Seropositivity for 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) autoantibodies supports the clinical diagnosis of necrotizing autoimmune myopathy (NAM). Confirmation with muscle biopsy is recommended. A paraneoplastic basis should be considered, according to age, sex, and other risk factors.(4) In cases of NAM, immune therapy is required and often multiple simultaneously utilized immunotherapies are needed to successfully treat patients.

Method Description

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° 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° 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)

Day(s) Performed

Monday through Friday

Clinical Reference

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

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

82397

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HMGCR HMG-CoA Reductase Ab, S 93493-5

 

Result ID Test Result Name Result LOINC Value
607414 HMG-CoA Reductase Ab, S 93493-5