Distinct immune activation patterns in adult-onset Still’s disease with fungal infections

Objective Fungal infections are uncommon but potentially life-threatening complications in adult-onset Still’s disease (AOSD). The immunological features of AOSD patients with fungal infections remain poorly defined, and this study aimed to characterize immune activation profiles in this population. Methods We retrospectively analyzed 277 patients diagnosed with AOSD, among whom 35 (12.6%) developed fungal infections. Clinical features and immunological parameters, including neutrophil CD64 (nCD64), myeloid-derived suppressor cells (MDSCs), activated T cells, and serum cytokine profiles, were compared between patients with and without fungal infections. Results Compared to non-infected AOSD patients, those with fungal infections had a higher frequency of splenomegaly (60.0% vs. 33.5%, p = 0.0024), pulmonary infiltrates (57.1% vs. 20.2%, p < 0.001), and pericarditis (42.9% vs. 20.7%, p = 0.0038). Immunologically, the infection group showed significantly elevated levels of nCD64 (45.39 vs. 11.16, p < 0.05) and enhanced CD8 + T cell activation, particularly CD8 + CD38 + T cells (81.54% vs. 66.89%, p < 0.05). Serum soluble IL-2R levels were also higher in infection patients (1884.18 vs. 1259.13 U/mL, p < 0.05). Cytokines such as IL-8, and IL-10 were markedly elevated during infection episodes. Additionally, ferritin elevation remained independently associated with fungal infection after adjusting for disease activity, MAS, and glucocorticoid exposure. Conclusions AOSD patients with fungal infections exhibit distinct immune activation patterns involving neutrophils and CD8 + T cells, reflecting dynamic immune changes during infection episodes. These immunological features may support integrated immune assessment and inform therapeutic considerations under immunosuppressive treatment.