Rare diseases of the immune system, Journal Year: 2024, Volume and Issue: unknown, P. 127 - 142
Published: Jan. 1, 2024
Language: Английский
Trends in Pharmacological Sciences, Journal Year: 2025, Volume and Issue: unknown
Published: Feb. 1, 2025
Idiopathic inflammatory myopathies (IIMs), or myositis, are rare diseases marked by immune-driven muscle damage and complications like skin lesions interstitial lung disease (ILD). Despite advances, challenges in diagnosis treatment persist, particularly inclusion body myositis (IBM), where no effective therapy exists. Recent breakthroughs, including transcriptomics insights into antibody-mediated immunity interferon (IFN) signaling, have clarified IIM pathophysiology spurred the development of new therapies, such as chimeric antigen receptor (CAR) T cells Janus kinase (JAK) inhibitors. We explore latest findings on mechanisms underlying adult-onset IIMs, emphasizing IBM pathobiology its unique immune degenerative pathways, a selective type 2 myofiber severe cell stress. Finally, we highlight recent advances transcriptomics, single-cell analysis, machine learning transforming research improving diagnostic accuracy, uncovering therapeutic targets, supporting personalized strategies.
Language: Английский
Citations
1
Seminars in Arthritis and Rheumatism, Journal Year: 2024, Volume and Issue: 68, P. 152474 - 152474
Published: June 3, 2024
To evaluate the efficacy and safety of Janus kinase inhibitors (JAKi) in treatment refractory anti-synthetase syndrome (ASS) real-world clinical settings. The medical records all ASS patients who were treated with JAKi from October 2020 to June 2023 retrospectively reviewed. Twenty included, (100%) had interstitial lung disease (ILD). After JAKi, 14 (70%) showed significant improvement manifestations, including arthritis (56.3% vs. 6.3%, p = 0.002), rash (77.8% 27.8%, 0.012), shortness breath (55.6% 16.7%, 0.039), cough (61.1% 11.1%, 0.012). Improvement was noted for myalgia (50% 0.016) muscular weakness while creatine (CK) levels, which abnormally elevated five prior treatment, significantly lowered (1096 ± 1042.98 IU/L 199.2 144.66 IU/L, 0.043). A decrease levels inflammatory markers, erythrocyte sedimentation rate (ESR) (p 0.001) C-reactive protein (CRP) 0.023) observed patients. In ASS-ILD, CT score reduced (188.75 69.67 156.35 74.62, 0.001). Furthermore, glucocorticoid dose (21.42 13.26 mg 11.32 8.59 mg; effective most as evidenced by improved skin rash, myositis, ILD. However, larger prospective controlled studies are required its efficacy.
Language: Английский
Citations
8
Inflammation and Regeneration, Journal Year: 2025, Volume and Issue: 45(1)
Published: Jan. 15, 2025
Abstract Idiopathic inflammatory myopathies (IIMs) are a group of autoimmune disorders characterized by immune cell infiltration muscle tissue accompanied inflammation. Treatment IIMs is challenging, with few effective therapeutic options due to the lack appropriate models that successfully recapitulate features observed in humans. In present study, we demonstrate immunodeficient mice transplanted human peripheral blood mononuclear cells (hPBMCs) exhibit key pathologic myositis humans and develop graft-versus-host disease. The hPBMC elevated serum levels creatine kinase aspartate transaminase, markers myositis, increased expression myositis-related genes, such as vascular adhesion molecule 1, intercellular amyloid A1, tissues. Histopathologic flow cytometric analyses reveal CD8 + T mice, similar patients particularly those polymyositis. Transplantation cell-depleted leads significant reduction polymyositis-like symptoms, agreement previous studies demonstrating main drivers Furthermore, transcriptome analysis from extensive upregulation characteristic genes polymyositis, providing further support accurately reflect pathophysiology Finally, administration prednisolone or tacrolimus, which commonly used for IIM treatment, alleviation findings. Therefore, propose should be considered model reflects patients.
Language: Английский
Citations
0
Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)
Published: April 1, 2025
Idiopathic inflammatory myopathies (IIM) are autoimmune disorders characterized by muscle inflammation and autoreactive B cell responses. The Janus kinase (JAK)-signal transducer activator of transcription (STAT) signaling pathway is essential for functions, making it a promising therapeutic target. This study explores the potential tofacitinib, JAK1/JAK3 inhibitor, to modulate activity in IIM. Peripheral populations from dermatomyositis (DM), anti-synthetase syndrome (ASyS) overlap myositis (OM) patients were analyzed flow cytometry. blood mononuclear cells (PBMC) or sorted memory cultured with tofacitinib stimulated combinations CD40, IL-21, IL-2, BAFF CpG. proliferation, differentiation (auto)antibody, cytokine/chemokine production assessed cytometry, Luminex, ELISA/ELiA assays. IIM peripheral compartment had elevated transitional naive cells, reduced Bmem frequencies compared healthy donors. Tofacitinib significantly inhibited CD40/IL-21-induced plasmablast formation function PBMC cell-only cultures across all subgroups, predominantly affecting IL-21-induced antibody production. Remarkably, levels anti-Jo1 autoantibodies, as well CXCL10 CXCL13 ASyS cultures. These findings highlight involvement IIM, evidenced altered composition active disease effective inhibition responses, including differentiation, (auto)antibody production, vitro. positions JAK/STAT new target
Language: Английский
Citations
0
International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3302 - 3302
Published: April 2, 2025
Idiopathic inflammatory myopathies are rare and complex representatives of systemic connective tissue diseases. Described initially as only two entities, recent advances in molecular imaging techniques now divide them into many subtypes, each with unique pathogenesis clinical phenotypes. Dermatomyositis its juvenile form the most prevalent subtypes characterized by vasculopathy humoral autoimmunity. Genetic predisposition environmental triggers initiate immune tolerance breakdown, leading to autoantibody production, complement activation, damage. Anti-synthetase syndrome primarily affects lungs, where responses aminoacyl-RNA synthetases drive vasculopathy, lung inflammation, fibrosis. Immune-mediated necrotizing muscle-specific, autoantibodies inducing fiber necrosis atrophy. Lastly, sporadic inclusion body myositis is a slowly progressive myopathy which dysfunctional protein handling autophagy more important pathogenic elements than muscle inflammation itself. The expanding basic science evidence can be overwhelming, making it challenging connect mechanisms manifestations. This review aims address this challenge presenting insights from practical perspective, reinforcing links between semiology.
Language: Английский
Citations
0
Mobile DNA, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 11, 2025
Language: Английский
Citations
0
Expert Review of Clinical Immunology, Journal Year: 2023, Volume and Issue: 19(11), P. 1385 - 1397
Published: Aug. 19, 2023
Janus kinase inhibitors (JAKi) have dramatically improved the treatment of various autoimmune and myeloproliferative disorders. Recently, concern has arisen regarding their safety in patients with rheumatoid arthritis.
Language: Английский
Citations
8
PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0296034 - e0296034
Published: May 16, 2024
Background Dermatomyositis (DM) is prone to nasopharyngeal carcinoma (NPC), but the mechanism unclear. This study aimed explore potential pathogenesis of DM and NPC. Methods The datasets GSE46239, GSE142807, GSE12452, GSE53819 were downloaded from GEO dataset. disease co-expression module was obtained by R-package WGCNA. We built PPI networks for key modules. ClueGO used analyze functional enrichment DEG analysis performed with "limma". “pROC” applied assess diagnostic performance hub genes. MiRNA-mRNA constructed using MiRTarBase miRWalk databases. Results modules that positively correlated NPC found. Its intersecting genes enriched in negative regulation viral gene replication pathway. Similarly, overlapping down-regulated DEGs also negatively regulated replication. Finally, we identified 10 primarily regulate biological processes type I interferon responses. Four (GBP1, IFIH1, IFIT3, BST2) showed strong performance, AUC>0.8. In both NPC, expression macrophage infiltration level. Based on genes’ miRNA-mRNA network, hsa-miR-146a plays a vital role DM-associated Conclusions Our research discovered pivot between Viral response may be crucial bridge By regulating genes, MiR-146a will provide new strategies diagnosis treatment complicated patients. For individuals persistent DM, screening cancer necessary.
Language: Английский
Citations
2
Current Issues in Molecular Biology, Journal Year: 2024, Volume and Issue: 46(2), P. 1150 - 1163
Published: Jan. 29, 2024
Ion channelopathies result from impaired ion channel protein function, due to mutations affecting transport across cell membranes. Over 40 diseases, including neuropathy, pain, migraine, epilepsy, and ataxia, are associated with channelopathies, impacting electrically excitable tissues significantly skeletal muscle. Gene transmembrane ionic flow strongly linked muscle disorders, particularly myopathies, disrupting excitability contraction. Electromyography (EMG) analysis performed on a patient who complained of weakness fatigue revealed the presence primary muscular damage, suggesting an early-stage myopathy. Whole exome sequencing (WES) did not detect potentially causative variants in known myopathy-associated genes but novel homozygous deletion P2RX6 gene likely function. The gene, predominantly expressed muscle, is ATP-gated receptor belonging purinergic receptors (P2RX) family. In addition, STRING pathways suggested correlation more proteins having plausible role No previous studies have reported implication this Further needed patients defective pathway, use vitro functional assays suppressing expression will be required validate its role.
Language: Английский
Citations
1
Clinical Immunology, Journal Year: 2024, Volume and Issue: 265, P. 110283 - 110283
Published: June 15, 2024
Overlapping clinical and pathomechanistic features can complicate the diagnosis treatment of inflammatory skin diseases, including psoriasis atopic dermatitis (AD). Spatial transcriptomics allows identification disease- cell-specific molecular signatures that may advance biomarker development future treatments. This study identified transcriptional in keratinocytes sub-basal CD4+ CD8+ T lymphocytes from patients with AD. In silico prediction ligand:receptor interactions delivered key signalling pathways (interferon, effector cells, stroma cell matrix biology, neuronal development, etc.). Targeted validation selected transcripts, CCL22, RELB, JUND, peripheral blood cells suggests chosen approach as a promising tool also other diseases. Psoriasis AD are characterized by dysregulation be targeted therapeutically. is valuable search for used biomarkers and/or therapeutic targets.
Language: Английский
Citations
1