Muscle Biopsy Findings in Combination With Myositis‐Specific Autoantibodies Aid Prediction of Outcomes in Juvenile Dermatomyositis

Abstract

ObjectiveJuvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis‐specific autoantibodies (MSAs) have prognostic significance in juvenile DM.MethodsMuscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow‐up 4.9 years). Long‐term treatment status (on or off medication over time) was modeled using generalized estimating equations.ResultsMuscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48‐fold higher odds (95% confidence interval [95% CI] 1.12–1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10‐fold higher odds (95% CI 1.01–1.21; P = 0.038). A protective effect was identified in patients with anti–Mi‐2 autoantibodies, in whom the odds of remaining on treatment were 7.06‐fold lower (95% CI 1.41–35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti–nuclear matrix protein 2 autoantibodies, anti–transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61‐fold higher odds (95% CI 1.16–2.22; P = 0.004), and for the total biopsy score, 1.13‐fold higher odds (95% CI 1.03–1.24; P = 0.013).ConclusionHistopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease.

Treatment of Juvenile Dermatomyositis: An Update

“…It is not known whether particular antibodies predate the specific features with which they are associated: they could be useful as prognostic biomarkers. In support of this, a recent study demonstrated that the MSA status in combination with the muscle biopsy score can be a significant prognostic tool [24].…”

Histological heterogeneity in a large clinical cohort of juvenile idiopathic inflammatory myopathy: analysis by myositis autoantibody and pathological features

“…In contrast, juvenile IIMs are rare and few sero‐pathological correlations have been reported. Our group has previously shown differences in histopathological severity between the MDA5 and Mi2 serological groups and described distinctive features of the paediatric patients positive for MDA5 . SRP and HMGCR serological groups appear to be associated with necrotizing myopathies in children as they are in adults .…”

“…As we have previously shown, muscle biopsy scores for patients with MDA5‐associated myopathies cluster in the mild range, Mi2‐associated cases cluster in the severe range, and TIF1γ‐ and NXP2‐associated cases vary across a wide range, Figure . To further analyse these findings, we conducted PCA using all 101 sets of biopsy score data.…”

“…Frozen sections were stained with Haematoxylin & Eosin, modified Gömöri trichrome (GT), NADH tetrazolium reductase and Acid Phosphatase. Immunohistochemical studies were performed as described previously . The following primary antibodies were used: anti‐human CD3 (UCHT1), anti‐human CD68 (KP1), anti‐human major histocompatibility complex class I heavy chain (W6/32) and anti‐human neonatal myosin (WB‐MHCn) from Novacastra, UK; anti‐human CD31 (JC70A) from Dako, Cambridgeshire, UK, and anti‐human C5b‐9 (Ae11) from Dako.…”

“…Serum or plasma were screened for autoantibodies using immunoprecipitation as described previously . The following controls were used as standard: Normal serum, anti‐Jo1, ‐PL7, ‐PL12, ‐Zo, ‐U1, ‐RNAPII, ‐PmScl, ‐Ro60, ‐La, ‐Mi2, ‐Ku, ‐SAE, ‐RNAPI/III, ‐U3, ‐TIF1γ, ‐SRP, ‐Scl70 and 140 kDa band.…”