This study examined CD38+HLA-DR+CD8+ T cells longitudinally across stages of Still's disease (SD) — at therapy-naïve onset (n=19), during clinically inactive disease (n=15), and at/prior to macrophage activation syndrome (MAS) onset (n=12) — using spectral flow cytometry, bulk RNA-sequencing, and in vitro IL-18 stimulation of healthy donor PBMCs.
CD38+HLA-DR+CD8+ T cells were expanded from SD onset (median 4.61%) and peaked in MAS (median 31.7%), compared to 0.87% in healthy donors; sustained in vitro IL-18 stimulation robustly reproduced this expansion and its key phenotypic features.
Small cohort sizes at each disease stage (n=12–19) limit statistical power; in vitro stimulation models may not fully replicate the complex in vivo milieu; causality between IL-18 and CD38+HLA-DR+CD8+ T cell expansion cannot be definitively established from this design.
CD38+HLA-DR+CD8+ T cells appear early in Still's disease and escalate sharply in MAS, suggesting monitoring this subset could help identify patients at risk for MAS. Targeting the IL-18 axis may be a strategy to interrupt this process before full MAS develops.
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