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

for the Childhood Myositis Heterogeneity Study Group

Research output: Contribution to journalArticle

21 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

All Science Journal Classification (ASJC) codes

  • Rheumatology

Cite this

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

@article{bdcf84fec4994f689460942de81d6b91,
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 = "{for the Childhood Myositis Heterogeneity Study Group} and 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 Linda Myers",
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pages = "1088--1094",
journal = "Arthritis Care and Research",
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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 - for the Childhood Myositis Heterogeneity Study Group

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 - Myers, Linda

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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U2 - 10.1002/acr.23113

DO - 10.1002/acr.23113

M3 - Article

VL - 69

SP - 1088

EP - 1094

JO - Arthritis Care and Research

JF - Arthritis Care and Research

SN - 2151-4658

IS - 7

ER -