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Query: UMLS:C0027121 (myositis)
 4,538 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dermatomyositis is a rare idiopathic inflammatory myopathy that affects adults and children, mostly female. Hallmarks of the disease are myositis with necrosis, regeneration and perifascicular atrophy accompanied by a typical skin rash with heliotrope erythema, Gottron's sign, Gottron's papules and nail fold changes with splinter hemorrhage. Typical skin symptoms may appear 6 months up to 2 years before muscle involvement (amyopathic dermatomyositis). New myositis-specific antibodies may allow clinicoserologic correlations within a heterogeneous clinical spectrum. Autoantibody profiles, subtype of myositis, overlap with other collagen vascular disorders and/or malignancy (paraneoplastic dermatomyositis) as well as age of the patients all have a considerable impact on course and prognosis. Infections, drugs and tumors may trigger activation of T and B cells, plasmacytoid dendritic cells, overproduction of type I interferons and complement-mediated endothelial cell damage resulting in vasculopathy. UV radiation may also trigger dermatomyositis. Oral corticosteroids (1.5-2.0 mg/kg body weight/day) are the mainstay of treatment until improvement of muscle symptoms and/or normalization of muscle enzymes with subsequent slow tapering. Corticosteroids may be given as monotherapy or combined with steroid-sparing immunosuppressive agents' i.e. azathioprine, methotrexate, mycophenolate mofetil or high-dose intravenous immunoglobulins. Prognosis has improved considerably since use of high-dose corticosteroids, from 50 to 90% response rate. New therapies with biologicals (anti-CD20-, anti-TNFalpha-, anti-interferon antibodies) and Janus kinase inhibitors are currently being evaluated.
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PMID:[Dermatomyositis-update]. 2621 26

Immunosuppressants used to treat autoimmunity are often not curative and have many side effects. Our purpose was to identify therapeutics for autoimmunity of the skeletal muscle termed idiopathic inflammatory myopathies (myositis). Recent evidence shows that the pro-inflammatory type I interferons (IFN) and a downstream product major histocompatibility complex (MHC) class I are pathogenic in myositis. We conducted quantitative high-throughput screening on >4500 compounds, including all approved drugs, through a series of cell-based assays to identify those that inhibit the type I IFN-MHC class I pathway in muscle precursor cells (myoblasts). The primary screen utilized CRISPR/Cas9 genome-engineered human myoblasts containing a pro-luminescent reporter HiBit fused to the C-terminus of endogenous MHC class I. Active compounds were counter-screened for cytotoxicity and validated by MHC class I immunofluorescence, Western blot, and RT-qPCR. Actives included Janus kinase inhibitors, with the most potent being ruxolitinib, and epigenetic/transcriptional modulators like histone deacetylase inhibitors and the hypoxia-inducible factor 1 inhibitor echinomycin. Testing in animal models and clinical trials is necessary to translate these therapies to myositis patients. These robust assay technologies can be further utilized to interrogate the basic mechanisms of the type I IFN-MHC class I pathway, identify novel molecular probes, and elucidate possible environmental triggers that may lead to myositis.
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PMID:High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle. 3245 68