Dermatomyositis (DM) is a rare and debilitating, systemic, autoimmune disease. While heterogenous in presentation and severity, DM is primarily characterised by a spectrum of skin and muscle disease, which may include proximal muscle weakness and recalcitrant cutaneous eruptions. DM may also be associated with joint pain and stiffness, inflammatory arthritis, dysphagia, fatigue, and calcinosis. The current standard of care for DM includes glucocorticoids, immunosuppressants, and intravenous immunoglobulin (IVIg). Unfortunately, these medications are not uniformly effective and can lead to adverse events, particularly with chronic use, necessitating discontinuation of therapy. Therefore, a substantial unmet need exists for more tailored and efficacious therapies that target DM pathogenesis. Brepocitinib is an oral, once-daily, novel, and specific TYK2/JAK1 inhibitor. Brepocitinib's potent inhibition of TYK2 and JAK1 reduces the signalling of pro-inflammatory cytokines, including IFN-α/β, IL-12, IL-23, and IFNγ, that have been implicated in the pathogenesis of DM. Other JAK inhibitors have been used off-label in both case series and open-label clinical trials in patients with DM; and brepocitinib has demonstrated efficacy in phase 2 clinical trials of several other autoimmune diseases, including plaque psoriasis, psoriatic arthritis, Crohn's disease, hidradenitis suppurativa, and ulcerative colitis. Therefore, there is a strong scientific and clinical rationale for the utility and potential effectiveness of brepocitinib in the treatment of DM patients. Currently, the safety, tolerability, and efficacy of brepocitinib is being evaluated in the largest (n=225) double-blind placebo-controlled phase 3 trial in DM patients to date (VALOR - NCT0543726).
- MeSH
- dermatomyozitida * farmakoterapie enzymologie imunologie diagnóza MeSH
- heterocyklické sloučeniny tricyklické * terapeutické užití škodlivé účinky farmakologie MeSH
- inhibitory Janus kinas * terapeutické užití škodlivé účinky MeSH
- inhibitory proteinkinas * terapeutické užití škodlivé účinky MeSH
- Janus kinasa 1 * antagonisté a inhibitory metabolismus MeSH
- kinasa TYK2 * antagonisté a inhibitory metabolismus MeSH
- lidé MeSH
- přemostěné cyklické sloučeniny MeSH
- pyrimidiny MeSH
- pyrroly * terapeutické užití škodlivé účinky MeSH
- signální transdukce účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene MeSH Prohlížeč
- heterocyklické sloučeniny tricyklické * MeSH
- inhibitory Janus kinas * MeSH
- inhibitory proteinkinas * MeSH
- JAK1 protein, human MeSH Prohlížeč
- Janus kinasa 1 * MeSH
- kinasa TYK2 * MeSH
- přemostěné cyklické sloučeniny MeSH
- pyrimidiny MeSH
- pyrroly * MeSH
- TYK2 protein, human MeSH Prohlížeč
- Klíčová slova
- Autoimmunity, Dermatomyositis, Gene Polymorphism, Polymyositis,
- MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- kinasa TYK2 genetika MeSH
- lidé MeSH
- myozitida genetika MeSH
- polymyozitida genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kinasa TYK2 MeSH
- TYK2 protein, human MeSH Prohlížeč
OBJECTIVE: Elevations of cell-free DNA (cfDNA) concentrations during hemodialysis (HD) sessions were reported in numerous studies regardless of an applied therapeutic protocol. It is generally thought that the elevated concentrations represent the consequence of apoptosis on the dialysis membranes. No data concerning the qualitative characteristics of cfDNAs in HD patients have been published till today; therefore, we focus on the promoter methylation status of genes involved in immune response. RESEARCH DESIGN AND METHODS: We isolated cfDNA from randomly selected patients before and after a HD session and from healthy subjects examined two times per day with 4 h interval. The extent of promoter methylation of 24 genes involved in immune response was examined using the 'EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity'. RESULTS: In our pilot study, we discovered significant changes in methylation patterns of genes IL-7, IL-13, IL-17C and TYK2 between HD patients and healthy subjects. CONCLUSION: Methylation of immune response genes promoters may be detected using EpiTect Methyl qPCR Array Inflammatory Response and Autoimmunity at the level of cfDNA to provide the information about the actual state of immune response in HD patients.
- MeSH
- bezbuněčný systém MeSH
- dialýza ledvin * MeSH
- DNA krev MeSH
- interleukiny genetika MeSH
- kinasa TYK2 genetika MeSH
- lidé MeSH
- metylace DNA * MeSH
- polymerázová řetězová reakce MeSH
- promotorové oblasti (genetika) * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA MeSH
- interleukiny MeSH
- kinasa TYK2 MeSH
- TYK2 protein, human MeSH Prohlížeč
