The levels of CXCL12 and its receptor, CXCR4, as a biomarker of disease activity and cutaneous manifestation in adult-onset Still's disease

Objective. This study evaluated the SDF-1/CXCL12 and soluble CXCR4 (sCXCR4) levels, and investigated their clinical relevance in adult-onset Still's disease (AOSD). Methods. Forty-two AOSD patients and 30 healthy controls (HC) were enrolled for serum sampling. Expression levels of CXCL12 and CXCR4 in skin biopsy materials of 40 AOSD patients, 10 patients with eczema, or 10 psoriasis, and 10 HC skin were evaluated with immunohistochemistry. Results. The serum CXCL12 levels in patients with AOSD (2,452 +/- 1,531 pg/mL) were higher than those in HC (1,708 +/- 1,322 pg/mL, p=0.017). The serum sCXCR4 levels in patients with AOSD (14,449 +/- 16,627 pg/mL) were higher than those in HC ( 3,046 +/- 2,554 pg/mL, p<0.001). Serum CXCL12 levels correlated positively with counts of leukocytes and neutrophils, erythrocyte sedimentation rate, ferritin, and C-reactive protein (CRP). Serum sCXCR4 levels correlated positively with systemic scores, platelet counts, and CRP levels. The serum levels of CXCL12 and sCXCR4 were decreased significantly in the patients with AOSD followed after resolution of disease activity. On immunohistochemical stain, the mean percentage of CXCR4-positive inflammatory cells was 51.4 +/- 27.5% and that of CXCL12-positive inflammatory cells was 16.7 +/- 13.3% in AOSD patients. CXCR4 was more frequently expressed in inflammatory cells from AOSD patients than in those with eczema or psoriasis and HC skin. Conclusion. These results demonstrate that sCXCR4 could be a clinical biomarker of evaluation for disease activity in AOSD, and show that CXCR4/CXCL12 may influence the inflammatory condition and skin manifestations of AOSD.