Association of Anti–3‐Hydroxy‐3‐Methylglutaryl‐Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients. Issue 7 (July 2017)

• Record Type: Journal Article
• Authors: Kishi, Takayuki; Rider, Lisa G.; Pak, Katherine; Barillas‐Arias, Lilliana; Henrickson, Michael; McCarthy, Paul L.; Shaham, Bracha; Weiss, Pamela F.; Horkayne‐Szakaly, Iren; Targoff, Ira N.; Miller, Frederick W.; Mammen, Andrew L.
• Other Names: Abramson Leslie S. investigator.; Albert Daniel A. investigator.; Baer Alan N. investigator.; Balboni Imelda M. investigator.; Ballinger Susan investigator.; Becker Mara investigator.; Bingham C. April investigator.; Bohnsack John F. investigator.; Botstein Gary R. investigator.; Carrasco Ruy investigator.; Cartwright Victoria W. investigator.; Chao Chun Peng T. investigator.; Cron Randy Q. investigator.; Curiel Rodolfo investigator.; DeGuzman Marietta M. investigator.; De la Pena Wendy investigator.; Eberhard B. Anne investigator.; Edelheit Barbara S. investigator.; Ellsworth Janet investigator.; Finkel Terri H. investigator.; Fuhlbrigge Robert C. investigator.; Gabriel Christos A. investigator.; Gedalia Abraham investigator.; Gewanter Harry L. investigator.; Goldmuntz Ellen A. investigator.; Goldsmith Donald P. investigator.; Gottlieb Beth S. investigator.; Graham Brent investigator.; Griffin Thomas A. investigator.; Haftel Hilary M. investigator.; Hannan William investigator.; Hennon Teresa investigator.; Hoeltzel Mark F. investigator.; Hollister J. Roger investigator.; Hopp Russell J. investigator.; Imundo Lisa F. investigator.; Jansen Anna investigator.; Jarvis James investigator.; Jerath Rita S. investigator.; Johnson Courtney R. investigator.; Jones Olcay Y. investigator.; Jung Lawrence K. investigator.; Kamdar Ankur investigator.; Katona Ildy M. investigator.; Kim Hanna investigator.; Kim Susan investigator.; Kingsbury Daniel J. investigator.; Klein Steven J. investigator.; Lang Bianca A. investigator.; Levine Johanan investigator.; Lindsley Carol B. investigator.; Mamyrova Gulnara investigator.; Mitchell Ray investigator.; Morishima Chihiro investigator.; Moser David W. investigator.; Murphy Frederick T. investigator.; Myers Linda K. investigator.; Nanda Kabita investigator.; Nativ Simona investigator.; Oral Elif A. investigator.; Ostrov Barbara E. investigator.; Pappu Ramesh investigator.; Parker Christopher T. investigator.; Passo Murray H. investigator.; Perez Maria D. investigator.; Person Donald A. investigator.; Punaro Marilyn G. investigator.; Rabinovich C. Egla investigator.; Rennebohm Robert M. investigator.; Rivas‐Chacon Rafael F. investigator.; Ronis Tova investigator.; Rosenkranz Margalit investigator.; Schiffenbauer Adam investigator.; Sheets Robert M. investigator.; Sherry David D. investigator.; Sills Edward M. investigator.; Sinal Sara H. investigator.; Stoll Matthew investigator.; Sule Sangeeta D. investigator.; Sundel Robert P. investigator.; Vehe Richard K. investigator.; Vogelgesang Scott A. investigator.; Wargula Jennifer C. investigator.; Yung Christine M. investigator.; Zemel Lawrence S. investigator.;
• Is Part Of: Arthritis care & research. Volume 69:Issue 7(2017:Jul.)
• Page Start: 1088
• Page End: 1094
• Publication Date: 2017-07
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/acr.23113
• Languages: English
• ISSNs: 2151-464X

Abstract

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.