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

Abstract

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.

239th ENMC International Workshop: Classification of dermatomyositis, Amsterdam, the Netherlands, 14–16 December 2018

“…In a recent study which included a detailed evaluation of 101 JDM biopsies the UK group has shown that severity of biopsy features is significantly different in different MSA groups with Mi2 positive cases having classic, severe features, MDA-5 positive cases having mild or minimal pathological changes. However, both the anti-TIF1-γ and anti-NXP2 positive groups were heterogeneous in terms of severity and features on biopsy [114] . Interestingly the degree of IFN driven expression of MxA protein in muscle biopsies was also found to be differentially expressed in different MSA groups as well as correlating with weakness as measured by the CMAS clinical score [115] .…”

TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features

“…The importance of TLR4 in DM is highlighted by the presence of TLR4+ cells in the perimysium of these patients [13]. Also, patients with anti-Mi2 antibodies are characterized by intense myositis and an abundant inflammatory infiltrate in muscle biopsy [52]. In this regard, TLR4 is a key mediator of the pathogenic autoimmune and inflammatory response in IIM.…”

Cutaneous manifestations of dermatomyositis characterized by myositis-specific autoantibodies

“…Both studies reported anti-MDA5 antibody to be strongly associated with ILD; however, only 8 (18%) of the 44 Japanese cases and none of the UK patients developed RP-ILD. A recent cohort study in the UK observed low myositis severity scores depending on muscle biopsies in 11 anti-MDA5 antibody-positive patients 15 .…”