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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.; Abramson, Leslie S.; Albert, Daniel A.; Baer, Alan N.; Balboni, Imelda M.; Ballinger, Susan; Becker, Mara; Bingham, C. April; Bohnsack, John F.; Botstein, Gary R.; Carrasco, Ruy; Cartwright, Victoria W.; Chao, Chun Peng T.; Cron, Randy Q.; Curiel, Rodolfo; DeGuzman, Marietta M.; De la Pena, Wendy; Eberhard, B. Anne; Edelheit, Barbara S.; Ellsworth, Janet; Finkel, Terri H.; Fuhlbrigge, Robert C.; Gabriel, Christos A.; Gedalia, Abraham; Gewanter, Harry L.; Goldmuntz, Ellen A.; Goldsmith, Donald P.; Gottlieb, Beth S.; Graham, Brent; Griffin, Thomas A.; Haftel, Hilary M.; Hannan, William; Hennon, Teresa; Hoeltzel, Mark F.; Hollister, J. Roger; Hopp, Russell J.; Imundo, Lisa F.; Jansen, Anna; Jarvis, James; Jerath, Rita S.; Johnson, Courtney R.; Jones, Olcay Y.; Jung, Lawrence K.; Kamdar, Ankur; Katona, Ildy M.; Kim, Hanna; Kim, Susan; Kingsbury, Daniel J.; Klein, Steven J.; Lang, Bianca A.; Levine, Johanan; Lindsley, Carol B.; Mamyrova, Gulnara; Mitchell, Ray; Morishima, Chihiro; Moser, David W.; Murphy, Frederick T.; Myers, Linda K.; Nanda, Kabita; Nativ, Simona; Oral, Elif A.; Ostrov, Barbara E.; Pappu, Ramesh; Parker, Christopher T.; Passo, Murray H.; Perez, Maria D.; Person, Donald A.; Punaro, Marilyn G.; Rabinovich, C. Egla; Rennebohm, Robert M.; Rivas‐Chacon, Rafael F.; Ronis, Tova; Rosenkranz, Margalit; Schiffenbauer, Adam; Sheets, Robert M.; Sherry, David D.; Sills, Edward M.; Sinal, Sara H.; Stoll, Matthew; Sule, Sangeeta D.; Sundel, Robert P.; Vehe, Richard K.; Vogelgesang, Scott A.; Wargula, Jennifer C.; Yung, Christine M.; Zemel, Lawrence S.
Arthritis Care and Research, July 2017, 2017-Jul, 2017-07-00, 20170701, Volume: 69, Issue: 7Journal Article
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.
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