Correlation of serum CX3CL1 level with disease activity in adult-onset Still's disease and significant involvement in hemophagocytic syndrome

Abstract

To investigate the characteristics of patients with adult-onset Still's disease (AOSD), serum cytokines and chemokines were measured to examine their associations with systemic manifestations of AOSD, especially hemophagocytic syndrome (HPS). Nineteen patients diagnosed with AOSD were enrolled. Serial serum samples were obtained from patients with AOSD in both active and inactive stages and controls. The concentrations of cytokines and chemokines, including IL-18, soluble IL-2 receptor (sIL-2R), CX3CL1, CXCL8, CXCL10, CCL2, and CCL3, were determined using enzyme-linked immunosorbent assay. Multivariate analysis was used to evaluate the correlations among serum chemokine levels, disease activity, and the clinical features of AOSD. Significantly higher serum levels of all cytokines and chemokines were observed in patients with active, untreated AOSD than in controls. The level of CX3CL1, but not other chemokines, was elevated in AOSD patients and was positively correlated with clinical activity and the levels of CRP, ferritin, IL-18, and sIL-2R. Among the 19 patients with AOSD, four patients also had HPS. Serum CX3CL1 and ferritin were significantly higher in AOSD patients with HPS than in those without HPS. The serum CX3CL1 level may be used as a clinical marker to assess the disease activity of AOSD, and high serum CX3CL1 and ferritin in patients with AOSD reflected the presence of HPS. The association between the chemokine profile and distinct clinical manifestations or various patterns of disease progression indicates that the pathogenesis of AOSD is heterogeneous.

Elevated circulating levels of the interferon-γ–induced chemokines are associated with disease activity and cutaneous manifestations in adult-onset Still’s disease

“…Proinflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF- α), IL-6, CXCL8, and IL-18, are elevated in acute AOSD patients67. Although the role of interferon-γ (IFN-γ) in AOSD is controversial, signature IFN-γ–induced cytokines or chemokines, such as IL-18 or C-X-C motif chemokine 10 (CXCL10), are significantly elevated in AOSD5678. Our previous study also showed that CXCL10 levels are elevated in AOSD patients compared with rheumatoid arthritis (RA) patients and healthy controls (HCs), and are correlated with AOSD disease activity markers9.…”

“…These CXCR3 ligands have been reported to mediate chemotactic and proliferative responses in collaboration or competition with each other13. Although CXCR3 ligands and their functions have been reported in autoimmune diseases, such as JIA and RA, relatively few studies have investigated the role of these chemokines in the pathogenesis of AOSD89151617.…”

Serum levels of fractalkine are associated with markers of insulin resistance in gestational diabetes

“…However, fractalkine remains independently and positively associated with the proinflammatory adipokine progranulin in our study. Interestingly, several other groups demonstrate a significant association between fractalkine on the one hand and markers of inflammation on the other in non‐pregnant humans , as well as rodents . Specific interactions between fractalkine and inflammatory pathways need to be studied in future experiments.…”

Adult-onset Still’s disease with macrophage activation syndrome diagnosed and treated based on cytokine profiling: a case-based review

“…In another study, Chen et al reported significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha in both sera and pathological tissues of 50 patients with active AOSD than in the tissues of 20 patients with active rheumatoid arthritis or 20 healthy controls [11]. Additionally, Kasama et al reported that the concentrations of cytokines and chemokines, including IL-18, soluble IL-2 receptor (sIL-2R), and CX3CL1, were significantly higher in patients with untreated, active AOSD than in controls [12]. Inoue et al reported that 33 patients with AOSD had a significant increase in IL-18 [5], and identified a characteristic cytokine profile pattern based on serum concentrations of IL-18, IL-6, neopterin, sTNF-RI, and sTNF-RII in AOSD [5].…”