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Type I interferon and mitochondrial dysfunction are associated with dysregulated cytotoxic CD8+ T cell responses in juvenile systemic lupus erythematosus.
Clin Exp Immunol
December 2024
Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH, GOSH, London, UK.
Juvenile systemic lupus erythematosus (JSLE) is an autoimmune condition which causes significant morbidity in children and young adults and is more severe in its presentation than adult-onset SLE. While many aspects of immune dysfunction have been studied extensively in adult-onset SLE, there is limited and contradictory evidence of how cytotoxic CD8+ T cells contribute to disease pathogenesis and studies exploring cytotoxicity in JSLE are virtually non-existent. Here, we report that CD8+ T cell cytotoxic capacity is reduced in JSLE versus healthy controls, irrespective of treatment or disease activity.
View Article and Find Full Text PDFBRAFV600E/pTERT double mutated papillary thyroid cancers exhibit immune gene suppression.
Front Endocrinol (Lausanne)
December 2024
Division of Endocrinology, Mayo Clinic, Jacksonville, FL, United States.
Introduction: BRAFV600E mutation (BRAF) is common in papillary thyroid cancer (PTC), and most patients have an excellent outcome. However, a TERT-promoter mutation (pTERT) in the presence of BRAF (BRAFpTERT) has been demonstrated to confer a more aggressive behavior to PTC. Lymphocytic infiltration is often present in PTC.
View Article and Find Full Text PDFMultimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.
Cancer Discov
December 2024
Brigham and Women's Hospital, Boston, MA, United States.
High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC.
View Article and Find Full Text PDFExploring emerging JAK inhibitors in the treatment of Aicardi-Goutières syndrome.
Expert Opin Emerg Drugs
December 2024
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Introduction: Aicardi-Goutières syndrome (AGS) is a genetically heterogeneous monogenic autoinflammatory disorder classified as an 'interferonopathy'. Nine genes have been implicated in AGS, encoding proteins involved in nucleic acid clearance, repair, sensing, or histone pre-mRNA processing. Dysregulation in these pathways leads to excessive type I interferon production, the primary driver of the disease.
View Article and Find Full Text PDFBiological hallmarks of systemic sclerosis are present in the skin and serum of patients with Very Early Diagnosis of SSc (VEDOSS).
Rheumatology (Oxford)
December 2024
Leeds Institute of Rheumatic and Musculoskeletal Medicine and Biomedical Research Centre, University of Leeds.
Objective: The Very Early Diagnosis of Systemic Sclerosis (VEDOSS) EUSTAR study showed that, despite not showing any clinical sign of disease, patients with Raynaud's and antinuclear antibodies and/or capillaroscopy abnormalities often progress to systemic sclerosis (SSc) within 5 years. We aimed to determine whether VEDOSS biosamples show biological SSc activity pre-clinically.
Methods: Skin biopsies were histologically analysed.
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