A new classification of inflammatory myopathies based on clinical manifestations and the presence of myositis-specific autoantibodies by multidimensional analysis

Les myopathies inflammatoires idiopathiques (MII) sont hétérogènes dans leurs physiopathologies et pronostics. L'émergence d'auto-anticorps spécifiques de myosites (ASM) suggère des sous-groupes plus homogènes de patients. Notre but est de trouver une nouvelle classification des MII fondée des critères phénotypiques, biologiques et immunologiques. Une étude observationnelle, rétrospective, multicentrique a été conduite à partir de la base de données du réseau français des myosites. Nous avons inclus 260 myosites, définies selon les classifications historiques pour la polymyosite (PM), la dermatomyosite (DM) et la myosite à inclusions (MI). Tous les patients ont eu au moins un dot myosite testant les anti-Jo1, anti-PL7, anti-PL12, anti-Mi-2, anti-Ku, anti-PMScl, anti-Scl70 and anti-SRP. Nous avons utilisé l'analyse des correspondances multiples suivie d'une classification hiérarchique ascendante afin d'agréger les patients dans des sous-groupes plus homogènes. Quatre clusters émergent. Le premier cluster (n=77) regroupe principalement des MI, avec des vacuoles bordées, des anomalies mitochondriales et de l'inflammation avec des fibres envahies. Le second cluster (n=91) était caractérisé par des myopathies nécrosantes auto-immunes (MNAi) en majorité, avec des anticorps anti-SRP et anti-HMGCR. Le troisième cluster (n=52) regroupe essentiellement des DM avec des anticorps anti-Mi-2, anti-MDA5, ou anti-TiF1 gamma. Le quatrième cluster (n=40) était défini par le SAS (n=36), avec notamment la présence des anti-Jo1 ou anti-PL7. Les critères histologiques sont dispensables pour la prédiction des clusters, soulignant l'importance d'une classification clinico-sérologique.Idiopathic inflammatory myopathies (IIM or myositis) are heterogeneous in their pathophysiology and prognosis. The emergence of myositis-specific autoantibodies (MSA) suggests homogenous subgroups of patients. Our aim was to find a new classification of IIM based on phenotypic, biological and immunological criteria. An observational, retrospective, multicentre study was led from the database of the myositis French network. We included 260 adult myositis, defined according to historical classifications for polymyositis (PM), dermatomyositis (DM) and inclusion body myositis (IBM). All patients did at least a screening with a line blot assays testing anti-Jo1, anti-PL7, anti-PL12, anti-Mi-2, anti-Ku, anti-PMScl, anti-Scl70 and anti-SRP. We performed multiple correspondence analysis and hierarchical clustering analysis to aggregate patients in homogenous subgroups. Four clusters emerged. The first cluster (n=77) regrouped primarily IBM patients with vacuolated fibres, mitochondrial abnormalities and inflammation with invaded fibres. The second cluster (n=91) was characterized by immune-mediated necrotizing myopathy (IMNM) in the majority of patients, with anti-SRP and anti-HMGCR antibodies. The third cluster (n=52) regrouped mainly DM patients with anti-Mi-2, anti-MDA5, or anti-TiF1 gamma antibodies. The fourth cluster (n=40) was defined by anti-synthetase syndrome (ASS), with the notable presence of anti-Jo1 or anti-PL7 antibodies. The histological criteria are dispensable for the prediction of the clusters, underlining the importance of a clinico-serological classification

The seasonality of Dermatomyositis associated with anti-MDA5 antibody: An argument for a respiratory viral trigger

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Dermatomyositis with anti-MDA5 auto-antibodies: is there a seasonal pattern of disease onset?

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Myostatin in idiopathic inflammatory myopathies: Serum assessment and disease activity

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Restoration of regulatory and effector T cell balance and B cell homeostasis in systemic lupus erythematosus patients through vitamin D supplementation.

International audienceABSTRACT: INTRODUCTION: Systemic lupus erythematosus (SLE) is a T and B cell-dependent autoimmune disease characterized by the appearance of autoantibodies, a global regulatory T cells (Tregs) depletion and an increase in Th17 cells. Recent studies have shown the multifaceted immunomodulatory effects of vitamin D, notably the expansion of Tregs and the decrease of Th1 and Th17 cells. A significant correlation between higher disease activity and lower serum 25-hydroxyvitamin D levels [25(OH)D] was also shown. METHODS: In this prospective study, we evaluated the safety and the immunological effects of vitamin D supplementation (100 000 IU of cholecalciferol per week for 4 weeks, followed by 100 000 IU of cholecalciferol per month for 6 months.) in 20 SLE patients with hypovitaminosis D. RESULTS: Serum 25(OH)D levels dramatically increased under vitamin D supplementation from 18.7±6.7 at day 0 to 51.4±14.1 (p<0.001) at 2 months and 41.5±10.1 ng/mL (p<0.001) at 6 months. Vitamin D was well tolerated and induced a preferential increase of naïve CD4+ T cells, an increase of regulatory T cells and a decrease of effector Th1 and Th17 cells. Vitamin D also induced a decrease of memory B cells and anti-DNA antibodies. No modification of the prednisone dosage or initiation of new immunosuppressant agents was needed in all patients. We did not observe SLE flare during the 6 months follow-up period. CONCLUSIONS: This preliminary study suggests the beneficial role of vitamin D in SLE patients and needs to be confirmed in randomized controlled trials

Different phenotypes in dermatomyositis associated with anti-MDA5 antibody

International audienceObjectives The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti–melanoma differentiation-associated gene 5 antibody–positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. Methods To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5−; n = 190/201) based on selected variables, collected retrospectively, without any missing data. Results Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5− patients with myositis. Conclusion Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist

In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case–control study

Background Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM).Objectives To assess the significance of DH/BS in patients with IM.Methods Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1.Results 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p&lt;0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p&lt;0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p&lt;0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p&lt;0.05).Conclusion In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis)