Morphological Characteristics of Idiopathic Inflammatory Myopathies in Juvenile Patients

Schänzer, Anne; Rager, L; Dahlhaus, Iris; Dittmayer, Carsten; Preuße, Corinna; Marina, Adela Della; Goebel, Hans‐Hilmar; Hahn, Andreas; Stenzel, Werner

doi:10.3390/cells11010109

Cited by 7 publications

(9 citation statements)

References 69 publications

(105 reference statements)

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“…Although this observation requires further investigation on larger groups of patients, the use of MHC-II immunostaining could be of great value for adult DM patients, as it could represent a new tool, easily usable in routine, to detect a paraneoplastic process. Regarding juvenile cases, in line with the present results, a recent study by Schänzer et al identified a positive MHC-II myofiber immunostaining in 7 out of 9 cases of juvenile DM, with a mild intensity and a scattered distribution, except for 2 cases which showed a perifascicular pattern [46]. Another study, in 2009, found MHC-II positive myofiber immunostaining in only 28% of juvenile DM muscles [45].…”

Section: Myofiber Mhc-ii Immunostaining a Tool For The Diagnosis Of I...supporting

confidence: 90%

“…Indeed, most previous studies were performed several decades ago, impeding the comparison with the currently used classification of IIM subgroups. Although few recent studies report interesting results, each of them analyzed only a particular subgroup [1, 4, 46], thus impeding the identification of MHC-II myofiber immunostaining variation between IIM subgroups.…”

Section: Discussionmentioning

confidence: 99%

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Input of Major Histocompatibility Complex class II immunostaining in idiopathic inflammatory myopathies

Lessard

Robert

Fenouil

et al. 2022

Preprint

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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.

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Section: Myofiber Mhc-ii Immunostaining a Tool For The Diagnosis Of I...supporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Input of Major Histocompatibility Complex class II immunostaining in idiopathic inflammatory myopathies

Lessard

Robert

Fenouil

et al. 2022

Preprint

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“…This notion is based on myopathological and immune features including the presence of MHC-I and MHC-II on myofibers [ 51 , 54 ]. MHC class I expression is evidenced on myofibers, showing an intriguing perifascicular pattern different from DM or IMNM patients [ 8 , 63 , 68 ]. MHC class I overexpression is further corroborated by changes to the muscle proteome of ASyS as compared to NDC.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis

et al. 2022

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Anti-synthetase syndrome (ASyS)-associated myositis is a major subgroup of the idiopathic inflammatory myopathies (IIM) and is characterized by disease chronicity with musculoskeletal, dermatological and pulmonary manifestations. One of eight autoantibodies against the aminoacyl-transferase RNA synthetases (ARS) is detectable in the serum of affected patients. However, disease-specific therapeutic approaches have not yet been established.To obtain a deeper understanding of the underlying pathogenesis and to identify putative therapeutic targets, we comparatively investigated the most common forms of ASyS associated with anti-PL-7, anti-PL-12 and anti-Jo-1. Our cohort consisted of 80 ASyS patients as well as healthy controls (n = 40), diseased controls (n = 40) and non-diseased controls (n = 20). We detected a reduced extent of necrosis and regeneration in muscle biopsies from PL-12+ patients compared to Jo-1+ patients, while PL-7+ patients had higher capillary dropout in biopsies of skeletal muscle. Aside from these subtle alterations, no significant differences between ASyS subgroups were observed. Interestingly, a tissue-specific subpopulation of CD138+ plasma cells and CXCL12+/CXCL13+CD20+ B cells common to ASyS myositis were identified. These cells were localized in the endomysium associated with alkaline phosphatase+ activated mesenchymal fibroblasts and CD68+MHC-II+CD169+ macrophages. An MHC-I+ and MHC-II+ MxA negative type II interferon-driven milieu of myofiber activation, topographically restricted to the perifascicular area and the adjacent perimysium, as well as perimysial clusters of T follicular helper cells defined an extra-medullary immunological niche for plasma cells and activated B cells. Consistent with this, proteomic analyses of muscle tissues from ASyS patients demonstrated alterations in antigen processing and presentation. In-depth immunological analyses of peripheral blood supported a B-cell/plasma-cell-driven pathology with a shift towards immature B cells, an increase of B-cell-related cytokines and chemokines, and activation of the complement system. We hypothesize that a B-cell-driven pathology with the presence and persistence of a specific subtype of plasma cells in the skeletal muscle is crucially involved in the self-perpetuating chronicity of ASyS myositis. This work provides the conceptual framework for the application of plasma-cell-targeting therapies in ASyS myositis.

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“…В настоящей работе антинуклеарный фактор в группе пациентов с ЮДМ выявлялся значимо реже, что представляется вполне закономерным и подтверждается данными других исследований [14]. Частота обнаружения миозит-ас-социированных аутоантител у наших больных с ЮИВМ была относительно невысока (10,8%).…”

Section: пациентыunclassified

“…Несмотря на отсутствие повышения содержания ферментов, все эти пациенты имели клинические проявления миопатического синдрома и подтверждение поражения мышц по данным игольчатой ЭНМГ либо визуализирующих методов.В настоящей работе дисфагия значимо реже наблюдалась при ОМ, чем при ЮДМ, а частота выявления клинических признаков дисфагии была несколько выше, чем в других исследованиях, в которых этот показатель составлял от 14,6 до 32%[9, 12,13].Изменения кожи у наших пациентов в целом схожи с описанными в литературе[9, 12,13]. Миопатический тип нарушений при капилляроскопии ногтевого ложа встречался у большинства пациентов, чаще в группе ЮДМ, тогда как, по данным других авторов, частота подобных изменений колеблется в очень широком диапазоне -от 7 до 81%[12,14]. Вероятно, это связано с разными воз-О Р И Г И Н А Л Ь Н Ы Е И С С Л Е Д О В А Н И Я / O R I G I N A L I N V ES T I G A T I O N S Современная ревматология.…”

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Juvenile idiopathic inflammatory myopathies: results of an open single-center retrospective study

Каледа¹,

Nikishina²,

Салугина³

et al. 2022

Sovremennaâ revmatologiâ

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Juvenile idiopathic inflammatory myopathies (JIIM) are rare diseases in which the prognosis is largely determined by timely diagnosis, timing of prescription and effectiveness of therapy.Objective: to characterize the clinical phenotypes, the results of paraclinical examination methods, the spectrum of autoantibodies, as well as therapeutic options in patients with JIIM.Patients and methods. The retrospective study included 37 patients with JIIM hospitalized in the pediatric department of the V.A. Nasonova Research Institute of Rheumatology from 2016 to 2020. All patients underwent a standard clinical and laboratory-instrumental examination in accordance with the diagnosis and severity of the condition.Results and discussion. Twenty-three of the 37 JIIM patients had juvenile dermatomyositis (JDM), 1 had polymyositis, and 13 had overlap-myositis (OM). The ratio of boys and girls was 1:1.7. The median age of onset for JDM was 6.9 years, and OM was 11.3 years. All patients had skeletal muscles involvement, dysphagia was detected in 52.2% of cases of JDM and in 15.4% of cases of OM. An increase in the level of creatine phosphokinase at the time of diagnosis was observed in 72.9% of patients, of lactate dehydrogenase – in 81.1%, of alanine aminotransferase - in 67.6%, of aspartate aminotransferase – in 75.7%. Heliotrope rash and/or Gottron's syndrome were observed in 100% of patients with JDM and in 30.8% with OM. Lung involvement was found in 27% of children. The myopathic capillaroscopic changes were present in 95.2% of patients with JDM and 53.8% with OM. Myositis-specific autoantibodies were found in 10.8% of patients with JIIM.All patients received glucocorticoids, 81.0% methotrexate, 18.9% hydroxychloroquine, 8.1% cyclophosphamide, 8.1% cyclosporine, 2.7% mycophenolate mofetil, 2.7% azathioprine, 67.6% - intravenous immunoglobulin. Biologic disease modifying antirheumatic drugs (bDMARDs) were prescribed to 26% of patients with JDM and to all patients with OM (only in 51.3% of cases with JIIM). The median duration of illness before initiation of bDMARDs therapy was 2.25 years. 58.8% of patients were treated with rituximab (RTM), 41.2% with abatacept (ABA). In 1 patient with OM, represented by a combination of systemic lupus erythematosus and JDM, three bDMARDs were used sequentially: ABA, etanercept and RTM. All patients achieved inactive disease status.Conclusion. JDM is the most common phenotype of JIIM, which is characterized by an earlier age of onset, skin involvement that precedes the development of myopathy, and typical capillaroscopic changes. The conclusion was made about the high efficacy and acceptable safety profile of bDMARDs therapy in children with JIIM, with careful monitoring of its tolerability. bDMARDs can be prescribed even in the early stages of the disease in the presence of unfavorable prognostic factors.

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Morphological Characteristics of Idiopathic Inflammatory Myopathies in Juvenile Patients

Cited by 7 publications

References 69 publications

Input of Major Histocompatibility Complex class II immunostaining in idiopathic inflammatory myopathies

Input of Major Histocompatibility Complex class II immunostaining in idiopathic inflammatory myopathies

Skeletal muscle provides the immunological micro-milieu for specific plasma cells in anti-synthetase syndrome-associated myositis

Juvenile idiopathic inflammatory myopathies: results of an open single-center retrospective study

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