Increased expression of CXCR 3 and its ligands in patients with vitiligo and CXCL 10 as a potential clinical marker for vitiligo

Abstract

BACKGROUND: Vitiligo is a skin disorder characterized by loss of melanocytes from the epidermis. A recent study reported that CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo, but there is very limited clinical data regarding this issue and little is known about the dynamic changes or correlations with disease severity of these chemokines throughout the disease course. OBJECTIVES: To present clinical data that supports and identifies the pathway of CXCR3 and its ligands in T-lymphocytic cell recruitment in vitiligo. METHODS: Cytometric bead array, flow cytometry, quantitative real-time polymerase chain reaction and immunohistology were used to examine their systemic and local expression in 80 patients with vitiligo and 40 controls. RESULTS: We showed that serum CXCL9 and CXCL10 were significantly elevated in patients with vitiligo and were higher in patients in progressive stages than in stable stages. The relative expression of CXCR3 mRNA in peripheral blood mononuclear cells was higher in vitiligo. There were higher percentages of both circulating CXCR3(+) CD4(+) and CXCR3(+) CD8(+) T cells in patients with progressive vitiligo compared with controls, while only the expression of CXCR3(+) CD8(+) T cells increased in patients with stable vitiligo. Histological findings also demonstrated an abundance of CXCR3(+) cells within vitiligo lesions. Furthermore, serum CXCL10 levels were associated with Vitiligo Area Scoring Index scores of patients with progressive vitiligo and were reduced after successful treatment. CONCLUSIONS: The CXCL10/CXCR3 axis mediates T-cell recruitment into the skin in progressive vitiligo. Blocking this chemotactic mechanism may present a new form of therapy. Serum CXCL10 may be a novel biomarker in monitoring disease activity and guiding treatment of progressive vitiligo.