Curr Opin Immunol. 2025 Aug 11;96:102632. doi: 10.1016/j.coi.2025.102632. Online ahead of print.
ABSTRACT
Juvenile idiopathic arthritis (JIA) is the most common rheumatological disorder affecting children. It is characterized by chronic synovial inflammation that may lead to permanent joint damage and disability. JIA is an umbrella term for a heterogenous group of subtypes based on specific clinical and serological features. Each subtype has a multifactorial pathogenesis that involves a complex interplay of genetic susceptibility, environmental triggers, and immune dysregulation. Recent advancements in genomic and multi-omics research have elucidated key genetic and epigenetic contributors to JIA, including risk loci within the highly polymorphic human leukocyte antigen region and monogenic mutations in genes, such as LACC1, UNC13D, and NFIL3. Genome-wide association studies have further revealed that many JIA-associated single-nucleotide polymorphisms (SNPs) reside in noncoding regulatory regions, underscoring the significance of chromatin architecture and transcriptional control in disease development. While current therapies – including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), biologics, and corticosteroids – offer symptomatic relief, they do not provide a cure, and many patients experience variable treatment responses or adverse effects. Emerging strategies focus on precision medicine approaches, integrating therapeutic biomarkers to predict disease course and optimize treatment. Furthermore, gene therapy using viral and mRNA-based vectors and advanced cell-based therapies – including regulatory T cells (Tregs), CAR-Tregs, and chimeric autoantibody receptor (CAAR)-T cells – are being explored as potential disease-modifying interventions. These innovative approaches aim to restore immune tolerance, reprogram dysregulated immune pathways, and minimize systemic immunosuppression. Although still in experimental stages, these technologies hold promise for achieving durable remission or potential cure in JIA. Continued translational research and clinical trials will be pivotal in realizing the therapeutic potential of these novel interventions.
PMID:40795628 | DOI:10.1016/j.coi.2025.102632