Year in Review: Novel Insights in the Pathogenesis of Spondyloarthritis - SPARTAN 2024 Annual Meeting Proceedings.

PURPOSE OF REVIEW: The canonical pathogenesis of spondyloarthritis (SpA) involves inflammation driven by HLA-B27, type 3 immunity, and gut microbial dysregulation. This review based on information presented at the SPARTAN meeting highlights studies on the pathogenesis of SpA from the past year, focusing on emerging mechanisms such as the roles of microbe-derived metabolites, microRNAs (miRNAs) and cytokines in plasma exosomes, specific T cell subsets, and neutrophils.

RECENT FINDINGS: The induction of arthritis in a preclinical model through microbiota-driven alterations in tryptophan catabolism provides new insights as to how intestinal dysbiosis may activate disease via the gut-joint axis. Immune activation may likewise be modulated by dysregulated miRNAs and cytokines contained in plasma exosomes, which appear to influence the homeostasis of both effector T cells and regulatory T cells (Tregs). Closer examination of T cells in animal models has uncovered distinct transcriptional and functional profiles between gut and joint Tregs, as well as highly specific T cell subsets that can be targeted to induce disease modification. Newer studies including both SpA patients and preclinical models have focused on the key role of neutrophils as drivers of inflammation and new bone formation in hypoxic, inflammation-driven tissue environments, potentially through interactions with adipocytes and mesenchymal stem cells. Functional studies and high-throughput techniques using samples from SpA patients and preclinical models have significantly enhanced our understanding of SpA pathogenesis, offering new insights into the specific mechanisms of immune regulation and identifying promising therapeutic targets.