ABSTRACT
BACKGROUND: Tissue expression of endothelial cell (EC) markers of microcirculatory changes in CSU is poorly investigated. OBJECTIVE: to explore the expression of specific EC markers (stem cell factor (SCF), vascular endothelial growth factor (VEGF) and membrane attack complex (MAC)) in CSU-L and CSU-NL skin through immunohistochemistry (IHC) and in serum. METHODS: Lesional (L) and non-lesional (NL) skin biopsies from CSU patients and HCs were studied for the IHC expression of SCF, VEGF and MAC in CSU patients (n = 23) and healthy controls (HCs, n = 9). In this population, we also investigated blood levels of VEGF and SCF. Patients were also assessed for clinical characteristics, disease activity, and markers of autoimmune CSU (aiCSU). RESULTS: Epidermal SCF reactivity was significantly higher in CSU-L skin compared to HC skin (p=0.026). In the dermis, SCF immunoreactivity was seen particularly on endothelial, perivascular and epithelial cells. In CSU-L skin, mean perivascular SCF stainings were significantly more intense compared to HCs (p<0.001). Furthermore, CSU-NL skin also showed significantly higher SCF stainings on dermal perivascular cells compared to HCs (p<0.001). CSU patients had the highest SCF immunoreactivity scores in the epidermis and/or on dermal ECs. These patients did not have significantly higher SCF serum levels. CONCLUSION: This is the first study to show elevated cutaneous expression of SCF in chronic spontaneous urticaria. These findings underline the potential therapeutic possibilities of anti-KIT antibodies in CSU treatment.
ABSTRACT
Chronic urticaria (CU) is a chronic inflammatory mast cell-driven disorder. Endothelial cells (ECs) contribute importantly to key features of CU. Several markers of EC (dys)function in CU have been reported, but have not yet been systematically reviewed. In this study, we systematically reviewed and categorized all published markers of EC functions in CU through a comprehensive search in Pubmed, The Cochrane Library, Web of Science, and SCOPUS using the following Mesh terms: CU AND pathogenesis AND (vasculopathy OR microangiopathy OR ECs OR marker). In total, 79 articles were selected and the identified biomarkers were categorized according to EC (dys)function in CU. The most frequent and consistently reported upregulated biomarkers in CU skin were adhesion molecules, TF, and P-selectin. The most frequently reported upregulated and reliable biomarkers in sera of CU patients were F1+2 for coagulation cascade involvement, D-dimers for fibrinolysis, and MMP-9 for vascular permeability. Emerging biomarkers described in the selected articles were endostatin, heat shock proteins, cleaved high molecular weight kininogen, and adipokines. This systematic review contributes to the pool of growing evidence for vascular involvement in CU where EC dysfunction is present in different aspects of cell survival, maintenance of vascular structure, and coagulation/fibrinolysis balance.