Background and objective:The idiopathic inflammatory myopathy Dermatomyositis (DM) is an acquired disease that combines muscle, lung and skin impairments. DM patients show a wide range of severity of proximal skeletal muscle weakness, associated with inflammatory infiltrates, vasculitis, and capillary dropout, perifascicular myofiber atrophy. Moreover, DM muscles show signs of muscle regeneration. Since muscle stem cells (MuSCs) are responsible for myofiber repair, we asked wether the proliferative properties of muscle stem cells (MuSCs) are altered in DM muscle. We investigated the role of type-I interferon (IFN-I) in this process since DM is associated with sustained inflammation with high IFN-I levels.Methods:MuSCs isolated from normal, adult and juvenile DM muscles were grown in culture and were analyzed in vitro for their proliferating properties, their myogenic capacities and their senescence. Gain and loss of function experiments were performed to assess the role of IFN-I signaling in the prolfierative capacities of MuSCs.Results:MuSCs derived from 8 DM adult patients (DM-MuSCs) (5 severe form and 3 mild form, established from histological evaluation), from 3 juvenile DM patients and from normal muscle were used to analyze their myogenesis in vitro. DM-MuSCs exhibited strongly reduced proliferating capacities as compared with healthy MuSCs (-31 to -43% for severe and mild DM, respectively), leading to poor myotube formation (-36 to -71%). DM-MuSCs were enriched in senescent, beta-galactosidase positive cells, explaining partly the proliferation defect. Gain and loss of function experiments were performed to assess the role of IFN-I on the proliferative capacity of MuSCs. High concentrations of IFN-I decreased the proliferation of healthy MuSCs. Similarly, conditioned-medium from DM-MuSCs decreased the proliferation of healthy MuSC (-15 to -22%), suggesting the delivery of an autocrine effector. Then, pharmacological blockade of the IFN signaling (using ruxolitinib or anti-IFN-receptor antibodies) in DM-MuSCs rescued their proliferation up to the control values.Discussion:These results show that autocrine IFN-I signaling prevents MuSC expansion, leading to muscle repair deficit. This process may explain the persistent muscle weakness observed in severe DM patients.
Gerber et al report 2 autosomal recessive pathogenic Misato homolog 1 (MSTO1) variants causing hereditary optic atrophy and raise concerns about a previously identified dominant variant of MSTO1 by Gal et al (2017).
Background. Idiopathic inflammatory myopathies (IIMs) are a group of rare acquired muscular diseases. In healthy muscle, myofibers do not express major histocompatibility complex (MHC) class I and II. It was established that MHC-I positive immunostaining, although non-specific, is a marker for IIM diagnosis, while the significance of MHC-II immunostaining remains unclear. The present study investigates the expression of MCH-II in myofibers and capillaries of IIM muscles, taking into account the current IIM classification. Patients & Methods. A historical cohort was designed, including dermatomyositis (DM), inclusion body myositis (IBM), anti-synthetase syndrome (ASyS), immune-mediated necrotizing myopathy (IMNM), or overlap myositis (OM). MHC-II immunostaining was performed on patient muscle sections and was analyzed in a standardized and blind manner. Results. Muscle sections from biopsies of 72 IIM patients were included: 23 DM, 17 IBM, 12 IMNM, 9 ASyS, and 11 OM. Overall, abnormal MHC-II immunostaining was found in myofibers and/or capillaries in 67 (93%) patients. Myofiber MHC-II immunostaining patterns differed according to the IIM subgroup: the immunostaining was diffuse in IBM (100%), negative in IMNM (75%), perifascicular in ASyS (67%), and either diffuse heterogeneous, clustered, or perifascicular in OM (27%, 27%, and 18%, respectively). MHC-II expression was found in 50% of DM (n=11/22). While all IIM subgroups presented quantitative and qualitative abnormalities of MHC-II immunostaining in capillaries, some subgroups displayed specificities. Most IBM and IMNM muscles presented frequent dilated capillaries (88% and 67%, respectively). DM, ASyS, and OM exhibited high frequencies of capillary lesions, including capillary dropout, leaky capillaries, and dilated capillaries. Conclusion. While recent expert opinion (EURO-NMD pathology working group) recommended that MHC-II immunostaining of muscle biopsy remains optional, the present work demonstrates that the expression pattern of MHC-II allows to distinguish between several IIM subgroups. Our data argue for the inclusion of MHC-II immunostaining in the routine histological diagnosis for IIMs.
Aims This study aimed to report the association of focal myositis (FM) and Behçet's disease (BD) and to analyse the main characteristics of such an association. Methods This is a retrospective multicentre study of patients with BD and FM (BD + FM+ group) and those without FM (BD − FM+ group). Clinical, laboratory, radiological, pathological, treatment and outcome data were analysed. Results The BD + FM+ group included 10 patients; the median [interquartile range] age at BD diagnosis was 25 [16–35] years, and at FM diagnosis, it was 30 [26–42] years. The diagnosis of BD preceded FM in the majority of cases (n = 8/10). FM occurrence was associated with BD flare‐ups in three cases. The creatine kinase levels remained normal or slightly increased. Histological analyses identified relatively preserved muscle tissue, associated with vasculitis (n = 5/6). All patients required treatment; most patients relapsed (n = 9/10). The BD − FM+ group included 35 patients. A comparison of the groups identified a trend towards a younger median age at diagnosis of FM among those with BD (p = 0.063) and more frequent focal muscle swelling in the BD + FM+ group (p = 0.029). The pathological analysis identified significantly less frequent muscle alterations in the BD + FM+ group (muscle fibre size heterogeneity, p = 0.021; necrosis, p = 0.007; and fibrosis, p = 0.027). BD + FM+ patients had a higher frequency of relapse (p = 0.003) and systematic treatment (p = 0.042). Conclusions FM occurring during BD appears to be part of the systemic vasculitis process and presents as a vasculitis‐associated focal myopathy with a specific clinico‐histological pattern. Patients with this association require long‐term follow‐up and adapted management. This case series also highlights the need for research on BD diagnostic criteria in cases of FM.
Objectives Idiopathic inflammatory myopathies are mainly defined by inflammatory infiltrates within the muscle (lymphocytes and macrophages). Eosinophil muscle infiltration has been described in idiopathic eosinophilic myositis (IEM) and rarely in eosinophilic fasciitis (EF). This study aimed to further delineate the nosological frame of idiopathic eosinophil muscle infiltration through the exhaustive analysis of IEM and EF patients. Methods This multicentre retrospective case series included IEM patients diagnosed between 2000 and 2022. IEM inclusion criteria were eosinophilic muscle infiltration with myositis pathological features, after the exclusion of differential diagnoses. An additional group of EF patients diagnosed between 2016 and 2022 was constituted. Inclusion criteria were an EF diagnosis and fascia thickening with inflammatory infiltrate. Results A total of 20 IEM cases and 10 EF cases were included. The median [IQR] age at diagnosis was 65 [49–70] years; there were 18 males. Data analysis delineated 4 subgroups: focal EM (FEM, n = 3), diffuse EM (DEM, n = 6), eosinophilic myofasciitis (EMF, n = 11), and EF (n = 10). FEM represented a limited and benign form of myositis. DEM cases presented objective muscle impairment with eosinophilic muscle infiltration. EMF patients presented subjective muscle impairment (myalgia, 55%), fasciitis (on histology and/or imaging), eosinophilic muscle infiltration, and frequent hypereosinophilia(55%). EF patients presented myalgia(50%), muscle lesions on histology with fascia-restricted inflammatory infiltrates with (60%) or without eosinophils(40%). Conclusions The analysis of IEM and EF patient characteristics delineates 4 subgroups (FEM, DEM, EMF, and EF) in terms of clinical, laboratory, imaging, pathological, and outcome specificities and proposes an adapted diagnostic and care management approach.
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