Journal article
Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB107:01 and Severe Myositis in Juvenile Myositis Patients
Arthritis care & research (2010), Vol.69(7), pp.1088-1094
07/01/2017
DOI: 10.1002/acr.23113
PMCID: PMC5487292
PMID: 28129483
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.
Details
- Title: Subtitle
- Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB107:01 and Severe Myositis in Juvenile Myositis Patients
- Creators
- Takayuki Kishi - National Institute of Environmental Health SciencesLisa G. Rider - National Institute of Environmental Health SciencesKatherine Pak - National Institute of Arthritis and Musculoskeletal and Skin DiseasesLilliana Barillas-Arias - Albany Medical Center HospitalMichael Henrickson - Cincinnati Children's Hospital Medical CenterPaul L. McCarthy - Yale UniversityBracha Shaham - Children's Hospital of Los AngelesPamela F. Weiss - Children's Hospital of PhiladelphiaIren Horkayne-Szakaly - Defense Health AgencyIra N. Targoff - University of Oklahoma Health Sciences CenterFrederick W. Miller - National Institute of Environmental Health SciencesAndrew L. Mammen - National Institute of Arthritis and Musculoskeletal and Skin DiseasesChildhood Myositis Heterogeneity Study Group
- Contributors
- Scott A Vogelgesang (Contributor) - University of Iowa, Internal Medicine
- Resource Type
- Journal article
- Publication Details
- Arthritis care & research (2010), Vol.69(7), pp.1088-1094
- Publisher
- Wiley
- DOI
- 10.1002/acr.23113
- PMID
- 28129483
- PMCID
- PMC5487292
- ISSN
- 2151-464X
- eISSN
- 2151-4658
- Number of pages
- 7
- Grant note
- National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) Myositis Association ZIAAR041203 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) National Institute of Arthritis and Musculoskeletal and Skin Diseases of the NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) ZIAES101074 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS)
- Language
- English
- Date published
- 07/01/2017
- Academic Unit
- Immunology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984359818502771
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