Recent advances and evolving concepts in Still’s disease

Deep Immunophenotyping of Circulating T and B Cells in Relapsing Adult-Onset Still’s Disease

“…It has been observed that initiating this class of drugs early is more effective and leads to a more enduring response. In refractory cases and in the development of HLH, Janus kinase inhibitors as well as interferon-gamma inhibitors are also considered [7]. Furthermore, the efficacy of canakinumab therapy on patients with sJIA, both clinically and in the laboratory, was demonstrated in clinical trials, where gene expression analysis was conducted three days after drug administration.…”

“…The etiology remains unknown, and the pathogenesis, considered a possible mixed (autoinflammatory > autoimmune) systemic inflammatory disease, involves the dysregulation of both the innate and adaptive immune systems [7]. On the one hand, gathered data suggest dysregulation within the innate immune system, reflecting the autoinflammatory nature of the disease, characterized by the activation of interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) signaling pathways [8].…”

“…Studies have shown increased nucleotide-binding oligomerization domain (NOD)-and leucine-rich repeat (LRR)-containing receptor pyrin domain-containing-3 (NLRP3) expression in peripheral blood mononuclear cells (PBMCs) from AOSD patients that positively correlates with disease activity [9]. On the other hand, a number of patients exhibit a genetic association with major histocompatibility complex (MHC) class II alleles [7], highlighting the potential influence of adaptive immunity (indicating an autoimmune origin of the disorder). This observation may elucidate why not all patients respond to therapy with IL-1 and IL-6 blockers, as well as the transition from a relapsing to a chronic course.…”

Juvenile idiopathic arthritis and primary ovarian failure: a two-sample Mendelian randomization analysis in a mixed-gender cohort

“…NK cells also demonstrate enrichment of proinflammatory pathways, reduced expression of immunomodulatory genes, and impaired cytotoxic functions. Furthermore, the compromised killing activity of NK cells may contribute to extensive activation and expansion of cytotoxic CD8 T lymphocytes, production of IFNγ and other macrophage activating factors, which in turn stimulate macrophages for prolonged periods, resulting in excessive activation and expansion of macrophages that induce the onset and progression of JIA through heightened inflammatory immune activation ( 28 ). Moreover, another study observed abnormal changes in NK cells following the same single-cell data analysis of POF ( 29 ); it can be inferred that these abnormal changes in NK cells predispose individuals to long-term inflammation, potentially contributing to ovarian dysfunction and diminished ovarian reserve.…”