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Test Code HMGES 3-Hydroxy-3-Methylglutaryl Coenzyme-A (HMG-CoA) Reductase, ELISA, Serum


Advisory Information


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 screen 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


Useful For

Evaluating patients with suspected necrotizing autoimmune myopathy

 

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

Method Name

Enzyme-Linked Immunosorbent Assay (ELISA)

Reporting Name

HMG-CoA ELISA, S

Specimen Type

Serum

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

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.

Reference Values

<20.0 U/mL

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.

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.

Method Description

IgG antibodies to 3-hydroxy-3- methylglutaryl coenzyme A reductase (HMGCR) are detected by an enzyme-linked immunosorbent assay (ELISA). An HMGCR fragment is immobilized to each well of a 96-well microtiter plate. Prediluted controls and patient samples are added to individual wells allowing antibodies reactive to HMGCR to bind. Unbound serum components are first washed away and then horseradish peroxidase conjugated to antihuman-IgG antibody is added to each well. After a second incubation, unbound conjugated antihuman-IgG antibody is washed away and a chromogenic substrate is added. After a brief incubation, the quantity of chromogenic substrate enzymatically converted to end-product is assessed using spectrophotometry. The measured absorbance at 450 nm is proportional to the quantity of IgG antibodies bound to HMGCR. Results are expressed in arbitrary units, which are derived from a calibration curve.(Package insert: QUANTA Lite HMGCR ELISA 704760 INOVA Diagnostics Inc, San Diego, CA 04/2014)

Day(s) and Time(s) Performed

Tuesday, Friday; 6 a.m.

Analytic Time

5 days

Specimen Retention Time

28 days

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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 U.S. Food and Drug Administration.

CPT Code Information

83516

LOINC Code Information

Test ID Test Order Name Order LOINC Value
HMGES HMG-CoA ELISA, S 93493-5

 

Result ID Test Result Name Result LOINC Value
603538 HMG-CoA ELISA, S 93493-5