Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy

Abstract

ObjectivesTo assess the value of major histocompatibility complex (MHC) class II antigen (HLA-DR) expression to distinguish anti-synthetase myopathy (ASM) from dermatomyositis (DM).MethodsMuscle biopsies from patients with ASM (n = 33), DM without anti-synthetase antibodies (ASAb) (n = 17), and normal muscle biopsy (n = 10) were first reviewed. ASAb included anti-Jo1 (26/33), anti-PL12 (4/33), anti-PL7 (2/33), and anti-EJ (1/33). Immunohistochemistry was performed for MHC-I/HLA-ABC, MHC-II/HLA-DR, membrane attack complex (C5b-9), neural cell adhesion molecule (NCAM)/CD56 expression, and inflammatory cell subsets. Twenty-four ASM and 12 DM patients from another center were added for HLA-DR evaluation.ResultsUbiquitous myofiber HLA-ABC expression was equally observed in ASM and DM (93.9% vs 100%, NS). In contrast, myofiber HLA-DR expression was found in 27/33 (81.8%) ASM (anti-Jo1: 23/26, 88.5%; others: 5/7, 71.4%) vs 4/17 (23.5%) DM patients (p < 0.001). HLA-DR was perifascicular in ASM, a pattern not observed in DM. In addition, C5b-9 deposition was observed on sarcolemma of non-necrotic perifascicular fibers in ASM, while, in DM, C5b-9was mainly detected in endomysial capillaries. CD8 cells were more abundant in ASM than in DM (p < 0.05), and electively located in perimysium or in perifascular endomysium. HLA-DR expression correlated positively with the CD8+ cells infiltrates. Strictly similar observations were made in the confirmatory study.ConclusionASM is characterized by strong myofiber MHC-II/HLA-DR expression with a unique perifascicular pattern, not described so far. HLA-DR detection must be included for routine myopathological diagnosis of inflammatory/dysimmune myopathies. HLA-DR expression in ASM may indicate a specific immune mechanism, possibly involving IFNγ.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0154-2) contains supplementary material, which is available to authorized users.

213th ENMC International Workshop: Outcome measures and clinical trial readiness in idiopathic inflammatory myopathies, Heemskerk, The Netherlands, 18–20 September 2015

“…PM, DM, IMNM, IBM, and non-specific myositis [2] since many patients cannot be incorporated into one of those subgroups, first because of interpretation discrepancies between pathologists. Jan de Bleecker introduced the fact that pathological criteria can be revisited in more homogenous groups of patients defined by their MSA, as has been published recently for myositis with anti-synthetase autoantibodies [24–26]. He proposed to continue developing and validating a set of identically assessed pathological abnormalities that can be used across different pathology labs.…”

“…However, patients with anti-Jo-1 autoantibodies also have prominent muscle fiber necrosis and HLA-II expression in perifascicular regions [24–26]. Patients with anti-Jo-1 autoantibodies have a perifascicular necrotizing myositis [25].…”

“…The level of evidence is sufficient today for the categorization of myositis with anti-synthetase autoantibodies, in that anti-Jo1 and other tRNA synthetase autoantibodies identify patients with a distinct disorder: the anti-synthetase syndrome [24–26]. For the other MSA, data suggest that these may also represent stable and mutually exclusive syndromes [30,31], and ongoing analyses of large cohorts of IIM patients may refine these findings.…”

Comparative analyses of muscle MRI and muscular function in anti-synthetase syndrome patients and matched controls: a cross-sectional study

“…The myositis component in ASS was described recently as a distinct histological entity [20–22]. However, as far as we know, there is no study investigating whether the acute and chronic stages of ASS are marked by a specific muscle MRI pattern.…”

The Clinical and Pathological Spectrum of Idiopathic Inflammatory Myopathies : Implications for pathogenesis, classification and diagnosis

“…It has however recently been repeatedly reported, and its detection is now recommended for IIM diagnostics [44], and has further been suggested as a distinctive marker for a specific IIM subgroup [45]. The classical co-stimulators (B7-1, B7-2) have not been detected in muscle fibers, although fibers have in IBM been reported to express the inducible co-stimulator ligand (ICOS-L), which may serve a similar purpose [46].…”