Recent Advances in Pharmacological Treatments of Adult Dermatomyositis

Chen, Kristen L.; Zeidi, Majid; Werth, Victoria P.

doi:10.1007/s11926-019-0850-9

Cited by 8 publications

(24 citation statements)

References 57 publications

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“…Increasing amounts of research suggests that the type I IFN signature likely contributes to DM pathogenesis 8 , 36 , 37 . Patients with DM have an increased type I IFN signature in the muscle, blood and skin, which has also been described in patients with SLE, RA, Sjogren's syndrome and system sclerosis 5 , 38 .…”

Section: Discussionmentioning

confidence: 99%

Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis

Li¹,

Bax²,

Patel³

et al. 2021

Theranostics

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Objectives: Extracellular vesicles (EVs) are lipid bilayer membrane vesicles that are present in various bodily fluids and have been implicated in autoimmune disease pathogenesis. Type I interferons (IFN), specifically IFN-β, are uniquely elevated in dermatomyositis (DM). The stimulator of interferon genes (STING) works as a critical nucleic acid sensor and adaptor in type I IFN signaling with possible implications in autoimmune diseases such as DM. In the current study, we investigated whether circulating EVs contribute to proinflammatory effects in DM, whether these proinflammatory responses are mediated by the STING signaling pathway, and if so, by what mechanism STING is activated. Methods: We collected and characterized EVs from plasma of healthy controls (HC) and DM patients; analyzed their abilities to trigger proinflammatory cytokines release by ELISA, and explored STING signaling pathway activation using immunoblot and immunofluorescent staining. STING signaling pathway inhibitors and RNAi were used to further investigate whether STING was involved in EVs-triggered proinflammatory response. DNase/lipid destabilizing agent was utilized to digest EVs and their captured DNA contents to evaluate how EVs triggered STING-mediated proinflammatory response in DM. Results: EVs isolated from DM plasma triggered proinflammatory cytokines including type I IFN release with STING signaling pathway activation. The activated STING pathway was preferentially mediated by dsDNA captured by EVs. Suppression of STING or its downstream signaling proteins attenuated the EVs-mediated proinflammatory response. Conclusions: Plasma-derived, DNA containing-EVs induced STING-mediated proinflammatory effects in DM. Targeting the STING pathway may be a potential therapeutic approach for DM.

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Section: Discussionmentioning

confidence: 99%

Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis

Li¹,

Bax²,

Patel³

et al. 2021

Theranostics

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“…Since B cell intracellular signals activate p38MAPK, inhibitors of p38MAPK may represent an alternative strategy in pemphigus when applied topically, thereby avoiding the severe adverse events observed with oral administration (61). Other small-molecule inhibitors include tofacitinib, a Janus kinase (JAK)-1/3 inhibitor, and ruxolitinib, a selective JAK-1/2 inhibitor, which suppress interleukin and interferon signaling in dermatomyositis (45). Although they have been used in a small number of patients, they proved promising.…”

Section: Discussion: Gilz-based Proteins As Potential Pharmacological Toolsmentioning

confidence: 99%

“…However, oral systemic GCs coupled with immunosuppressants are generally used as therapy for both skin and muscle diseases. Other drugs include biologicals such as rituximab, abatacept, and tocilizumab (45).…”

Section: Rare Pathologies That Require Gc Treatmentmentioning

confidence: 99%

A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool?

et al. 2021

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Since their discovery, glucocorticoids (GCs) have been used to treat almost all autoimmune and chronic inflammatory diseases, as well as allergies and some forms of malignancies, because of their immunosuppressive and anti-inflammatory effects. Although GCs provide only symptomatic relief and do not eliminate the cause of the pathology, in the majority of treatments, GCs frequently cannot be replaced by other classes of drugs. Consequently, long-term treatments cause adverse effects that may, in turn, lead to new pathologies that sometimes require the withdrawal of GC therapy. Therefore, thus far, researchers have focused their efforts on molecules that have the same efficacy as that of GCs but cause fewer adverse effects. To this end, some GC-induced proteins, such as glucocorticoid-induced leucine zipper (GILZ), have been used as drugs in mouse models of inflammatory pathologies. In this review, we focus on some important but rare autoimmune and chronic inflammatory diseases for which the biomedical research investment in new therapies is less likely. Additionally, we critically evaluate the possibility of treating such diseases with other drugs, either GC-related or unrelated.

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“…For DM therapy, MTX can be administered orally or subcutaneously at the dose of 10-25 mg/week. The drug is effective both in relation to muscle ailments and skin lesions [39,40]. The unquestionable advantage of MTX over AZA is the speed of response.…”

Section: Methotrexatementioning

confidence: 99%

Dermatomyositis. Diagnostic and therapeutic recommendations of the Polish Dermatological Society

Reich¹,

Lis‐Święty²,

Krasowska³

et al. 2021

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Dermatomyositis is an autoimmune disease characterized by skin lesions and/or symptoms of myositis. In addition to the so-called classic dermatomyositis the following forms of dermatomyositis are distinguished based on the clinical presentation: pediatric, paraneoplastic, drug-induced and amyopathic. A number of disease-specific autoantibodies are identified in dermatomyositis (including anti-Mi2, anti-TIF1, anti-NXP2, anti-SAE or anti-MDA5), presence of which may be associated with a specific clinical phenotype. The diagnosis of the severity of muscle involvement is currently based mainly on physical examination, deviations in results of laboratory investigations, electromyographic examination and imaging examination, mainly with the use of magnetic resonance imaging. Systemic glucocorticosteroids administered as monotherapy or in combination with other immunosuppressants remain the mainstay of dermatomyositis treatment, and in the absence of satisfactory improvement, intravenous immunoglobulins are used. In addition, in case of interstitial lung disease, the use of cyclophosphamide may be necessary. The choice of a therapy, as well as the rate of dose reduction, depend on the dynamics of the disease, symptoms, diagnosed immunological disorders, as well as comorbidities and the drugs used. Each diagnostic and therapeutic decision must take into account the individual clinical data of the patient and current scientific reports.

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Recent Advances in Pharmacological Treatments of Adult Dermatomyositis

Cited by 8 publications

References 57 publications

Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis

Plasma-derived DNA containing-extracellular vesicles induce STING-mediated proinflammatory responses in dermatomyositis

A Glance at the Use of Glucocorticoids in Rare Inflammatory and Autoimmune Diseases: Still an Indispensable Pharmacological Tool?

Dermatomyositis. Diagnostic and therapeutic recommendations of the Polish Dermatological Society

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