APRIL 2024 to JULY 2024
Author: Daliya Pencheva and Piotr Kuszmiersz
AUTUMN 2024 Press Review – Miscellaneous
Digital acceptance and commitment therapy for fibromyalgia
Gendreau et al. (10.1016/S0140-6736(24)00909-7) conducted a phase 3, multi-centre, randomized controlled trial evaluating a 12-week self-guided digital acceptance and commitment therapy (ACT) program for fibromyalgia management. The PROSPER-FM trial included 275 adults with fibromyalgia randomized to digital ACT (n=140) or active control (n=135) groups. At 12 weeks, 71% of ACT participants reported improvement on the Patient Global Impression of Change scale versus 22% of controls (difference 48.4%, 95% CI 37.9-58.9, p<0.0001). The digital ACT intervention was found to be safe and efficacious compared to digital symptom tracking for managing fibromyalgia in adults. This smartphone-delivered program could potentially improve access to cognitive behavioral therapy for fibromyalgia patients.
ETS2: A key regulator of macrophage inflammation in rheumatic diseases
Stankey et al. (10.1038/s41586-024-07501-1) identified ETS2 as a central regulator of inflammatory responses in human macrophages, with implications for multiple rheumatic diseases. Using functional genomics, the authors showed that genetic variation at the chr21q22 locus increases ETS2 expression by enhancing pioneer factor binding to a distal enhancer. This locus is associated with ankylosing spondylitis and Takayasu’s arteritis, among other conditions. Elevated ETS2 levels drive a pro-inflammatory macrophage phenotype characterized by increased cytokine production, phagocytosis, and ROS generation. The authors demonstrated that pharmacological inhibition of upstream ETS2 regulators, like MEK1/2, could suppress this inflammatory program in patient samples, highlighting potential therapeutic avenues for rheumatic diseases.
Bispecific T Cell Engagers (BiTEs) Kill B Cells by Engaging T Cells
Bucci et al. (10.1038/s41591-024-02964-1) explored the use of bispecific T cell engagers (BiTEs) in treating refractory rheumatoid arthritis (RA). Six patients with multidrug-resistant RA were treated with the CD19xCD3 BiTE blinatumomab, resulting in effective B cell depletion and a concomitant decrease in T cells, confirming the BiTEs’ engager function. The treatment led to rapid improvements in clinical disease activity, synovitis, and autoantibody levels. Importantly, he safety profile was favorable, with no severe cytokine-release syndrome. These promising results highlight the potential of BiTEs as a novel therapeutic option for B cell-mediated autoimmune diseases like RA.
Gender differences in IL-17-producing cells in ankylosing spondylitis
Lee et al. (10.55563/clinexprheumatol/do7osn) investigated transcriptomic differences in IL-17-enriched peripheral blood mononuclear cells between male and female ankylosing spondylitis (AS) patients. RNA sequencing of samples from 21 AS patients revealed distinct gene expression patterns between genders. Males showed upregulation of TGF-β, PGE2, and S100 proteins, while IL-12B levels were lower compared to females. Genes involved in Th17 differentiation also exhibited differential expression between genders. These findings may contribute to understanding the phenotypic differences observed between male and female AS patients.
Muscle-bone cross-talk in osteoporosis mediated by FNIP1-TFEB-IGF2 axis
Mao et al. (10.1126/scitranslmed.adk9811) investigated the mechanisms underlying muscle dysfunction-related bone loss in limb-girdle muscular dystrophy (LGMD). They found decreased expression of folliculin-interacting protein 1 (FNIP1) in muscle tissue of LGMD patients, associated with reduced bone mineral density. In mouse models, muscle-specific FNIP1 deletion led to decreased bone mass and increased osteoclastic activity. Mechanistically, FNIP1 deficiency caused nuclear translocation of transcription factor EB (TFEB), activating insulin-like growth factor 2 (IGF2) transcription and secretion. Muscle-derived IGF2 stimulated osteoclastogenesis through IGF2 receptor signaling. Serum IGF2 levels negatively correlated with bone health in humans with osteoporosis. This FNIP1-TFEB-IGF2 axis represents a potential therapeutic target for musculoskeletal diseases and osteoporosis.
Daliya Pencheva
Daliya obtained her PhD from the Medical University of Sofia, Bulgaria, with a focus on the management of systemic lupus erythematosus. She completed her residency in rheumatology at the Clinic of Rheumatology, University Hospital “St. Ivan Rilski,” Sofia, Bulgaria. Daliya is also an assistant professor of pathophysiology at the Department of Physiology and Pathophysiology, Medical University of Sofia. Her major interests include patient-reported outcome measures, quality of life, and treat-to-target strategies. Daliya is a member of the Country Liaison Sub-Committee.
Piotr Kuszmiersz
Piotr is a PhD in Medical Sciences and an Internal Medicine Specialist, currently undertaking his rheumatology training at the Department of Rheumatology and Immunology, Jagiellonian University Medical College in Kraków, Poland. His research interests focus on Patient-Reported Outcome Measures, epidemiology, and the application of AI in medicine. Piotr is a member of the EMEUNET Social Media Sub-Committee.