Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07: 01 and Severe Myositis in Juvenile Myositis Patients

Takayuki Kishi, Lisa G. Rider, Katherine Pak, Lilliana Barillas-Arias, Michael Henrickson, Paul L. McCarthy, Bracha Shaham, Pamela F. Weiss, Iren Horkayne-Szakaly, Ira N. Targoff, Frederick W. Miller, Andrew L. Mammen, Leslie S. Abramson, Daniel A. Albert, Alan N. Baer, Imelda M. Balboni, Susan Ballinger, Mara Becker, C. April Bingham, John F. BohnsackGary R. Botstein, Ruy Carrasco, Victoria W. Cartwright, Chun Peng T. Chao, Randy Q. Cron, Rodolfo Curiel, Marietta M. DeGuzman, Wendy De la Pena, B. Anne Eberhard, Barbara S. Edelheit, Janet Ellsworth, Terri H. Finkel, Robert C. Fuhlbrigge, Christos A. Gabriel, Abraham Gedalia, Harry L. Gewanter, Ellen A. Goldmuntz, Donald P. Goldsmith, Beth S. Gottlieb, Brent Graham, Thomas A. Griffin, Hilary M. Haftel, William Hannan, Teresa Hennon, Mark F. Hoeltzel, J. Roger Hollister, Russell J. Hopp, Lisa F. Imundo, Anna Jansen, C. Egla Rabinovich, for the Childhood Myositis Heterogeneity Study Group

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1088-1094
Number of pages7
JournalArthritis Care and Research
Volume69
Issue number7
DOIs
StatePublished - Jul 1 2017

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Myositis
Coenzyme A
Autoantibodies
Oxidoreductases
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Alleles
Creatine Kinase
Juvenile dermatomyositis
HLA-DRB1 Chains
Muscles
Muscular Atrophy
Muscle Weakness
Arthralgia
Contracture
Muscular Diseases
Immunosuppressive Agents
Exanthema

ASJC Scopus subject areas

  • Rheumatology

Cite this

Kishi, T., Rider, L. G., Pak, K., Barillas-Arias, L., Henrickson, M., McCarthy, P. L., ... for the Childhood Myositis Heterogeneity Study Group (2017). Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07: 01 and Severe Myositis in Juvenile Myositis Patients. Arthritis Care and Research, 69(7), 1088-1094. https://doi.org/10.1002/acr.23113

Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07 : 01 and Severe Myositis in Juvenile Myositis Patients. / 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; Rabinovich, C. Egla; for the Childhood Myositis Heterogeneity Study Group.

In: Arthritis Care and Research, Vol. 69, No. 7, 01.07.2017, p. 1088-1094.

Research output: Contribution to journalArticle

Kishi, T, Rider, LG, Pak, K, Barillas-Arias, L, Henrickson, M, McCarthy, PL, Shaham, B, Weiss, PF, Horkayne-Szakaly, I, Targoff, IN, Miller, FW, Mammen, AL, Abramson, LS, Albert, DA, Baer, AN, Balboni, IM, Ballinger, S, Becker, M, Bingham, CA, Bohnsack, JF, Botstein, GR, Carrasco, R, Cartwright, VW, Chao, CPT, Cron, RQ, Curiel, R, DeGuzman, MM, De la Pena, W, Eberhard, BA, Edelheit, BS, Ellsworth, J, Finkel, TH, Fuhlbrigge, RC, Gabriel, CA, Gedalia, A, Gewanter, HL, Goldmuntz, EA, Goldsmith, DP, Gottlieb, BS, Graham, B, Griffin, TA, Haftel, HM, Hannan, W, Hennon, T, Hoeltzel, MF, Hollister, JR, Hopp, RJ, Imundo, LF, Jansen, A, Rabinovich, CE & for the Childhood Myositis Heterogeneity Study Group 2017, 'Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07: 01 and Severe Myositis in Juvenile Myositis Patients', Arthritis Care and Research, vol. 69, no. 7, pp. 1088-1094. https://doi.org/10.1002/acr.23113
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 ; Rabinovich, C. Egla ; for the Childhood Myositis Heterogeneity Study Group. / Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07 : 01 and Severe Myositis in Juvenile Myositis Patients. In: Arthritis Care and Research. 2017 ; Vol. 69, No. 7. pp. 1088-1094.
@article{060122358bb043b787768006c5cb54fb,
title = "Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07: 01 and Severe Myositis in Juvenile Myositis Patients",
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.",
author = "Takayuki Kishi and Rider, {Lisa G.} and Katherine Pak and Lilliana Barillas-Arias and Michael Henrickson and McCarthy, {Paul L.} and Bracha Shaham and Weiss, {Pamela F.} and Iren Horkayne-Szakaly and Targoff, {Ira N.} and Miller, {Frederick W.} and Mammen, {Andrew L.} and Abramson, {Leslie S.} and Albert, {Daniel A.} and Baer, {Alan N.} and Balboni, {Imelda M.} and Susan Ballinger and Mara Becker and Bingham, {C. April} and Bohnsack, {John F.} and Botstein, {Gary R.} and Ruy Carrasco and Cartwright, {Victoria W.} and Chao, {Chun Peng T.} and Cron, {Randy Q.} and Rodolfo Curiel and DeGuzman, {Marietta M.} and {De la Pena}, Wendy and Eberhard, {B. Anne} and Edelheit, {Barbara S.} and Janet Ellsworth and Finkel, {Terri H.} and Fuhlbrigge, {Robert C.} and Gabriel, {Christos A.} and Abraham Gedalia and Gewanter, {Harry L.} and Goldmuntz, {Ellen A.} and Goldsmith, {Donald P.} and Gottlieb, {Beth S.} and Brent Graham and Griffin, {Thomas A.} and Haftel, {Hilary M.} and William Hannan and Teresa Hennon and Hoeltzel, {Mark F.} and Hollister, {J. Roger} and Hopp, {Russell J.} and Imundo, {Lisa F.} and Anna Jansen and Rabinovich, {C. Egla} and {for the Childhood Myositis Heterogeneity Study Group}",
year = "2017",
month = "7",
day = "1",
doi = "10.1002/acr.23113",
language = "English (US)",
volume = "69",
pages = "1088--1094",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
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TY - JOUR

T1 - Association of Anti–3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07

T2 - 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

PY - 2017/7/1

Y1 - 2017/7/1

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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