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Arthritis Care Res (Hoboken). 2017 Jul;69(7):1088-1094. doi: 10.1002/acr.23113.

Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients.

Author information

1
National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, Maryland.
2
Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
3
Albany Medical Center, Albany, New York.
4
Cincinnati Children's Medical Center, Cincinnati, OH.
5
Yale University School of Medicine, New Haven, Connecticut.
6
Children's Hospital of Los Angeles, Los Angeles, California.
7
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
8
Joint Pathology Center, Defense Health Agency, Silver Spring, Maryland.
9
Veterans Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma.

Abstract

OBJECTIVE:

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.

METHODS:

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).

RESULTS:

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.

CONCLUSION:

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.

PMID:
28129483
PMCID:
PMC5487292
[Available on 2018-07-01]
DOI:
10.1002/acr.23113
[Indexed for MEDLINE]
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