Background CXCL10 is produced in response to interferon-γ, and tumor necrosis factor-α triggers the accumulation of activated lymphocytes via interaction with a specific receptor, CXCR3, creating an amplification feedback loop. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation, and CXCR3 and CXCR5 are known to serve as receptors for CXCL13.

Objectives It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD.

Methods Blood samples were collected from 39 active AOSD patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6±9.2 months later. CXCL10, CXCL13, and CXCR3 expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry.

Results The CXCL10 level of AOSD patients (1,031.3±2,019.62 pg/mL) was higher than that of HC (104.35±47.92 pg/mL, p=0.006). Also, the CXCL13 level of AOSD patients (158.8±151.2 pg/mL) was higher than that of HC (23.5±18.1 pg/mL, p<0.001). Serum CXCL10 levels correlated with ferritin and aspartate transaminase levels, and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. Also, serum CXCL10 levels correlated with those of CXCL13. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (p=0.002 and p=0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 0 to 85% (mean, 25.77±23.28%), CXCL13 from 1 to 72% (mean, 23.27±22.17%), and CXCR3 from 2 to 65% (mean, 16.35±18.54%). The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p=0.01). CXCL13 levels were correlated with those of CD4 (r=0.453, p=0.02) and CD68 (r=0.464, p=0.017).

Conclusions Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations in AOSD.

References

1. Manzo A, Vitolo B, Humby F, et al. Mature antigen-experienced T helper cells synthesize and secrete the B cell chemoattractant CXCL13 in the inflammatory environment of the rheumatoid joint. Arthritis Rheum 2008;58:3377-3387.

2. Kasama T, Furuya H, Yanai R, et al. Correlation of serum CX3CL1 level with disease activity in adult-onset Still's disease and significant involvement in hemophagocytic syndrome. Clin Rheumatol 2012;31:853-860.

3. Laragione T, Brenner M, Sherry B, et al. CXCL10 and its receptor CXCR3 regulate synovial fibroblast invasion in rheumatoid arthritis. Arthritis Rheum 2011;63:3274-3283.

Disclosure of Interest None declared