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HelpMayo Test ID HMGCR 3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase, 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
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
Useful For
Evaluating patients with suspected necrotizing autoimmune myopathy
Measuring 3-hydroxy-3-methylglutaryl-CoA reductase antibodies
Method Name
Chemiluminescence Immunoassay (CIA)
Reporting Name
HMG-CoA Reductase Ab, SSpecimen Type
SerumSpecimen 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 |
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 onset 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.
Reference Values
<20.0 CU
Interpretation
Seropositivity for 3-hydroxy-3-methylglutaryl-CoA reductase 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.
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 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 Reference
1. Kassardjian CD, Lennon VA, Alfugham NB, Mahler M, Milone M. Clinical features and treatment outcomes of necrotizing autoimmune myopathy. JAMA Neurol. 2015;72(9):996-1003
2. Emslie-Smith AM, Engel AG. 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;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;139(Pt 8):2131-2135
5. Christopher-Stine L, Casciola-Rosen L, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;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;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;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;87(10):1038-1044
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 from the RLU value obtained for each sample.(Package insert: QUANTA Flash HMGCR 701333. Inova Diagnostics, Inc; V04, 09/2018)
Day(s) Performed
Monday through Friday
Report Available
2 to 4 daysSpecimen Retention Time
28 daysPerforming Laboratory
Mayo Clinic Laboratories in Rochester
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 |