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2017 ; 69
(7
): 1088-1094
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Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase
Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients
#MMPMID28129483
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
Arthritis Care Res (Hoboken)
2017[Jul]; 69
(7
): 1088-1094
PMID28129483
show ga
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.