title: Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients.
abstract: Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of juvenile anti-HMGCR-positive myositis patients.
  
  
  
  The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti-HMGCR-positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis-specific autoantibodies (MSAs).
  
  
  
  Five of 440 patients (1.1%) were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and 2 patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/liter. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR-positive subjects compared to MSA-negative patients or those with other MSAs. Anti-HMGCR-positive patients had only partial responses to multiple immunosuppressive medications, and their disease often took a chronic course. The DRB1*07:01 allele was present in all 5 patients, compared to 26.25% of healthy controls (corrected P = 0.01); none of the 5 juvenile patients had DRB1*11:01.
  
  
  
  Compared to children with other MSAs, muscle disease appears to be more severe in those with anti-HMGCR autoantibodies. Like adults, children with anti-HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, in anti-HMGCR-positive children, there is a strong association with HLA-DRB1*07:01.
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kishi
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Rider
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Katherine
authors.initials: K
authors.lastname: Pak
authors.affiliation: Albany Medical Center, Albany, New York.
authors.forename: Lilliana
authors.initials: L
authors.lastname: Barillas-Arias
authors.affiliation: Cincinnati Children's Medical Center, Cincinnati, OH.
authors.forename: Michael
authors.initials: M
authors.lastname: Henrickson
authors.affiliation: Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Paul L
authors.initials: PL
authors.lastname: McCarthy
authors.affiliation: Children's Hospital of Los Angeles, Los Angeles, California.
authors.forename: Bracha
authors.initials: B
authors.lastname: Shaham
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Pamela F
authors.initials: PF
authors.lastname: Weiss
authors.affiliation: Joint Pathology Center, Defense Health Agency, Silver Spring, Maryland.
authors.forename: Iren
authors.initials: I
authors.lastname: Horkayne-Szakaly
authors.affiliation: Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.
authors.forename: Ira N
authors.initials: IN
authors.lastname: Targoff
authors.affiliation: National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland.
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Miller
authors.affiliation: Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mammen
mesh_terms: D000214:Acyl Coenzyme A / Q000097:blood*; D000293:Adolescent; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D009220:Myositis / Q000097:blood* / Q000175:diagnosis*; D009419:Nerve Tissue Proteins / Q000097:blood*; D016601:RNA-Binding Proteins / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D000214:Acyl Coenzyme A; D001323:Autoantibodies; D015415:Biomarkers; D009419:Nerve Tissue Proteins; C467044:RBM45 protein, human; D016601:RNA-Binding Proteins; C008047:3-hydroxy-3-methylglutaryl-coenzyme A