CD34 stromal expression is inversely proportional to smooth muscle actin expression and extent of morphea

Abstract

Background Fibrosis is thought to be the main pathophysiology of scleroderma, and myofibroblasts play the main role in abnormal fibrotic pathologies. Altered distribution of dermal dendritic cells (DDCs) and vascular abnormalities has been reported to relate to the pathogenesis of scleroderma. Objective Methods To investigate fibrotic pathogenesis of morphea (localized scleroderma) by demonstrating the relative expression and distribution of DDCs and myofibroblasts, we performed immunohistochemical stains using several relevant antibodies. Skin lesions of 50 patients with morphea and age-, sex- and site-matched normal skin of 50 subjects were evaluated for the following antibodies: CD34, factor XIIIa (FXIIIa), smooth muscle actin (SMA), CD31 and vascular cell adhesion molecule-1 (VCAM-1). Results Conclusions CD34 stromal stain was significantly lower in patients than controls (P = 0.000), while FXIIIa, SMA and VCAM-1 stains were significantly higher in patients than controls (P = 0.043, P = 0.000 and P = 0.027, respectively). In subtype analysis within patients, CD34 stromal stain showed decreasing trends with increasing disease extent and increasing fibrosis, respectively. CD34 stromal stain showed an inverse correlation and mutually exclusive spatial expression pattern with SMA stain (r = -0.286, P = 0.044). The inverse relationship was maintained in each dermal layer analysis, upper and lower dermis (r = -0.397, P = 0.004 and r = -0.281, P = 0.048, respectively). Mutually exclusive staining patterns of CD34 stromal and SMA stains suggest a phenotypic change of CD34+ DDCs into SMA+ myofibroblasts with increasing disease extent and fibrosis in morphea. Degree of loss of CD34+ DDCs can be a useful marker in predicting the extent and severity of morphea.