Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy

Arthritis Rheum. 2012 Dec;64(12):4087-93. doi: 10.1002/art.34673.


Objective: Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are found in patients with statin-associated immune-mediated necrotizing myopathy and, less commonly, in statin-unexposed patients with autoimmune myopathy. The main objective of this study was to define the association of anti-HMGCR antibody levels with disease activity.

Methods: Anti-HMGCR levels, creatine kinase (CK) levels, and strength were assessed in anti-HMGCR-positive patients. Associations of antibody level with CK level and strength at visit 1 were analyzed in 55 patients, 40 of whom were exposed to statins. In 12 statin-exposed and 5 statin-unexposed patients with serum from 5 serial visits, the evolution of antibody levels, CK levels, and strength was investigated.

Results: Antibody levels were associated with CK levels (P < 0.001), arm strength (P < 0.05), and leg strength (P < 0.05) at visit 1, but these associations were only significant among statin-exposed patients in stratified analyses. With immunosuppressive treatment over 26.2 ± 12.6 months (mean ± SD), antibody levels declined (P < 0.05) and arm abduction strength improved (P < 0.05) in the 17 patients followed up longitudinally. The separate analysis showed that statin-exposed patients developed decreased antibody levels (P < 0.01), decreased CK levels (P < 0.001), improved arm strength (P < 0.05), and improved hip flexion strength (P < 0.05) with treatment. Anti-HMGCR antibody levels did not normalize in any patient.

Conclusion: In the entire cohort, initial anti-HMGCR levels correlated with indicators of disease activity; with immunosuppressive treatment, antibody levels declined and arm strength improved. Statin-exposed patients had significant improvements in CK levels and strength whereas statin-unexposed patients did not, suggesting a phenotypic difference between statin-exposed and statin-unexposed anti-HMGCR-positive patients.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / physiopathology
  • Biopsy
  • Creatine Kinase / blood*
  • Female
  • Humans
  • Hydroxymethylglutaryl CoA Reductases / drug effects
  • Hydroxymethylglutaryl CoA Reductases / immunology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Male
  • Middle Aged
  • Muscle Strength / drug effects
  • Muscle Strength / physiology*
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology
  • Muscular Diseases / drug therapy
  • Muscular Diseases / immunology*
  • Muscular Diseases / physiopathology
  • Phenotype
  • Severity of Illness Index*
  • Time Factors
  • Treatment Outcome


  • Autoantibodies
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunosuppressive Agents
  • HMGCR protein, human
  • Hydroxymethylglutaryl CoA Reductases
  • Creatine Kinase