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Aim: Juvenile idiopathic inflammatory myopathies have been recently reclassified into clinico‐serological subgroups. Myopathological correlates of the subgroups are incompletely understood. Methods: We studied muscle biopsies from 101 children with clinically and serologically defined juvenile idiopathic inflammatory myopathies from the UK JDM Cohort and Biomarker Study by applying the international JDM score tool, myopathological review and C5b‐9 complement analysis. Results: Autoantibody data were available for 90/101 cases with 18/90 cases positive for anti‐TIF1γ, 15/90 anti‐NXP2, 11/90 anti‐MDA5, 5/90 anti‐Mi2 and 6/90 anti‐PmScl. JDM biopsy severity scores were consistently low in the anti‐MDA5 group, high in the anti‐Mi2 group, and widely distributed in the other groups. Biopsies were classified histologically as perifascicular atrophy (22/101), macrophage‐rich necrosis (6/101), scattered necrosis (2/101), clustered necrosis (2/101), inflammatory fibre invasion (2/101), chronic myopathic change (1/101), diffuse endomysial macrophage infiltrates (40/101) and minimal change (24/101). MDA5 cases segregated with the minimal change group and showed no capillary C5b‐9‐deposition. The Mi2 group displayed high severity scores and a tendency towards sarcolemmal complement deposition. NXP2 and TIF1γ groups showed a variety of pathologies with a high proportion of diffuse endomysial macrophage infiltrates and a high proportion of capillary C5b‐9 deposition. Conclusion: We have shown that juvenile idiopathic inflammatory myopathies have a spectrum of histopathological phenotypes and show distinct complement attack complex deposition patterns. Both correlate in some cases with the serological subtypes. Most cases do not show typical histological features associated with dermatomyositis (e.g. perifascicular atrophy). In contrast, more than half show relatively mild histopathological changes. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the relationship between expression of myxovirus‐resistance protein A (MxA) protein on muscle biopsies by immunohistochemistry and disease activity in juvenile dermatomyositis (JDM) patients. Also, another aim was to investigate whether the expression of MxA is related with myositis‐specific autoantibodies (MSA) status in JDM patients. Methods: 103 patients (median aged 6.3, interquartile range 0.5–15.9) enrolled in the Juvenile Dermatomyositis Cohort and Biomarker Study (JDCBS). Muscle biopsies were stained with MxA and scored. Clinical data at initial presentation were collected and autoantibodies were analysed. Multiple linear regression analysis was performed to estimate the association between MxA expression on muscle fibres and muscle disease activity, and MSA status. Results: Expression of MxA protein on JDM samples was identified in 61.2%. There was a significant association between MxA scores and Childhood Myositis Assessment Scale (CMAS) (P = 0.002), and Manual Muscle Testing of Eight Muscles (MMT8) (P = 0.026). CMAS and MMT8 scores were significantly lower in the group of patients with strong MxA expression. MxA scores differed according to MSA subgroups (P = 0.002). Patients with positive nuclear matrix protein 2 autoantibodies had strong MxA expression, whereas anti‐melanoma differentiation‐associated gene 5 positive patients had no or weak MxA expression. Conclusions: This study reveals the significant association between level of MxA expression on muscle fibres and clinical measures of muscular disease activity in JDM patients and MSA status. This confirms type I interferonopathies in muscle fibres of JDM patients which could help with improving treatment outcome in JDM patients and underscoring the distinct pathophysiological pathways in different MSA status. [ABSTRACT FROM AUTHOR]