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Arthritis Care Res (Hoboken). 2017 Jan 27. doi: 10.1002/acr.23113. [Epub ahead of print]

Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies are Associated with DRB1*07:01 and Severe Myositis in Pediatric Myositis Patients.

Author information

1
Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD.
2
Muscle Disease Unit, Laboratory of Muscle Stem Cells and Gene Expression, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD.
3
Albany Medical Center, Albany, NY.
4
Cincinnati Children's Medical Center, Cincinnati, OH.
5
Yale University School of Medicine, New Haven, CT.
6
Children's Hospital of Los Angeles, Los Angeles, CA.
7
Children's Hospital of Philadelphia, Philadelphia, PA.
8
Joint Pathology Center, Defense Health Agency, Silver Spring, MD.
9
Veteran's Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.

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 pediatric 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 (1.1%) of 440 patients were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and two patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/L. 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 often a chronic course. The DRB1*07:01allele was present in all 5 patients compared to 26.25% of healthy controls (Pcorrected=0.01); none of the 5 pediatric patients had DRB1*11:01.

CONCLUSIONS:

Compared to children with other MSAs, muscle disease appeared 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, anti-HMGCR-positive children have a strong association with HLA DRB1*07:01. This article is protected by copyright. All rights reserved.

PMID:
28129483
DOI:
10.1002/acr.23113
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