E Reefman1, H Kuiper, P C Limburg, C G M Kallenberg, M Bijl. 1. Departments of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. ereefman@scientist.com
Abstract
OBJECTIVE: To investigate the involvement of type I interferons and endothelial cell adhesion molecules in the development of ultraviolet B (UVB)-induced systemic lupus erythaematosus (SLE) skin lesions. METHODS: A total of 19 SLE patients and 13 controls were irradiated with two minimal erythaemal doses(MED) of UVB. Subsequently, skin biopsies were analysed (immuno) histologically over 10 days, for expression of IFNalpha-induced MxA, numbers of plasmacytoid dendritic cells (pDC), and expression of endothelial cell adhesion molecules, namely E-selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was compared to its expression in nine established cutaneous lupus erythaematosus(CLE) lesions of SLE patients. RESULTS: Before irradiation IFNalpha-induced MxA was expressed at significantly higher levels in non-lesional skin of SLE patients compared to healthy controls. In patients developing infiltrates upon UVB irradiation, MxA expression increased further, reaching expression levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA expression was sustained up to day 10, in contrast to patients not developing infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid dendritic cells (pDC) were detected in nonirradiated skin or at any time after UVB exposure in SLE patients or controls. MxA expression correlated with influx of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM-1. CONCLUSION: Development of UVB-induced SLE skin lesions involves a skewing towards production of Th1-associated cytokines, such as IFNalpha. In turn, this may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T-cells and macrophages.
OBJECTIVE: To investigate the involvement of type I interferons and endothelial cell adhesion molecules in the development of ultraviolet B (UVB)-induced systemic lupus erythaematosus (SLE) skin lesions. METHODS: A total of 19 SLEpatients and 13 controls were irradiated with two minimal erythaemal doses(MED) of UVB. Subsequently, skin biopsies were analysed (immuno) histologically over 10 days, for expression of IFNalpha-induced MxA, numbers of plasmacytoid dendritic cells (pDC), and expression of endothelial cell adhesion molecules, namely E-selectin, ICAM-1, and L-selectin ligand. Additionally, MxA expression was compared to its expression in nine established cutaneous lupus erythaematosus(CLE) lesions of SLEpatients. RESULTS: Before irradiation IFNalpha-induced MxA was expressed at significantly higher levels in non-lesional skin of SLEpatients compared to healthy controls. In patients developing infiltrates upon UVB irradiation, MxA expression increased further, reaching expression levels similar to or exceeding levels in CLE-skin lesions. In these patients, MxA expression was sustained up to day 10, in contrast to patients not developing infiltrates in whom expression decreased. No noteworthy numbers of plasmacytoid dendritic cells (pDC) were detected in nonirradiated skin or at any time after UVB exposure in SLEpatients or controls. MxA expression correlated with influx of T-cells and monocytes/macrophages, and with expression of E-selectin and ICAM-1. CONCLUSION: Development of UVB-induced SLE skin lesions involves a skewing towards production of Th1-associated cytokines, such as IFNalpha. In turn, this may lead to up-regulation of E-selectin and ICAM-1 resulting in recruitment of T-cells and macrophages.
Authors: Jason S Knight; Venkataraman Subramanian; Alexander A O'Dell; Srilakshmi Yalavarthi; Wenpu Zhao; Carolyne K Smith; Jeffrey B Hodgin; Paul R Thompson; Mariana J Kaplan Journal: Ann Rheum Dis Date: 2014-08-07 Impact factor: 19.103