title: Antibody levels correlate with creatine kinase levels and strength in anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors.forename: Jessie L
authors.initials: JL
authors.lastname: Werner
authors.forename: Lisa
authors.initials: L
authors.lastname: Christopher-Stine
authors.forename: Sharon R
authors.initials: SR
authors.lastname: Ghazarian
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Pak
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Kus
authors.forename: Natalie R
authors.initials: NR
authors.lastname: Daya
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Lloyd
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mammen
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D001706:Biopsy; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000187:drug effects / Q000276:immunology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009135:Muscular Diseases / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D010641:Phenotype; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D001323:Autoantibodies; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; C553220:HMGCR protein, human; D006903:Hydroxymethylglutaryl CoA Reductases; D003402:Creatine Kinase