TY - JOUR
T1 - Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients
AU - Kishi, Takayuki
AU - Rider, Lisa G.
AU - Pak, Katherine
AU - Barillas-Arias, Lilliana
AU - Henrickson, Michael
AU - McCarthy, Paul L.
AU - Shaham, Bracha
AU - Weiss, Pamela F.
AU - Horkayne-Szakaly, Iren
AU - Targoff, Ira N.
AU - Miller, Frederick W.
AU - Mammen, Andrew L.
AU - Abramson, Leslie S.
AU - Albert, Daniel A.
AU - Baer, Alan N.
AU - Balboni, Imelda M.
AU - Ballinger, Susan
AU - Becker, Mara
AU - Bingham, C. April
AU - Bohnsack, John F.
AU - Botstein, Gary R.
AU - Carrasco, Ruy
AU - Cartwright, Victoria W.
AU - Chao, Chun Peng T.
AU - Cron, Randy Q.
AU - Curiel, Rodolfo
AU - DeGuzman, Marietta M.
AU - De la Pena, Wendy
AU - Eberhard, B. Anne
AU - Edelheit, Barbara S.
AU - Ellsworth, Janet
AU - Finkel, Terri H.
AU - Fuhlbrigge, Robert C.
AU - Gabriel, Christos A.
AU - Gedalia, Abraham
AU - Gewanter, Harry L.
AU - Goldmuntz, Ellen A.
AU - Goldsmith, Donald P.
AU - Gottlieb, Beth S.
AU - Graham, Brent
AU - Griffin, Thomas A.
AU - Haftel, Hilary M.
AU - Hannan, William
AU - Hennon, Teresa
AU - Hoeltzel, Mark F.
AU - Hollister, J. Roger
AU - Hopp, Russell J.
AU - Imundo, Lisa F.
AU - Jansen, Anna
AU - Rabinovich, C. Egla
AU - for the Childhood Myositis Heterogeneity Study Group
N1 - Publisher Copyright:
© 2017, American College of Rheumatology
PY - 2017/7
Y1 - 2017/7
N2 - 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.
AB - 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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U2 - 10.1002/acr.23113
DO - 10.1002/acr.23113
M3 - Article
C2 - 28129483
AN - SCOPUS:85021292049
SN - 2151-464X
VL - 69
SP - 1088
EP - 1094
JO - Arthritis Care and Research
JF - Arthritis Care and Research
IS - 7
ER -