Division of Dermatology, Tohoku Medical and Pharmaceutical University, Sendai, Japan.
Department of Medical Laboratory Science, Faculty of Health Sciences, Hokkaido University, Sapporo, Japan.
J Dermatol. 2022 Dec;49(12):1233-1237. doi: 10.1111/1346-8138.16523. Epub 2022 Jul 25.
We previously reported that IgA vasculitis and cutaneous arteritis could be dependently associated with the presence of the antiphosphatidylserine/prothrombin complex (anti-PS/PT) antibody and lysosomal-associated membrane protein-2 (LAMP-2). The copy number of LAMP-2 mRNA in skin tissue samples from rats with cutaneous vasculitis induced by intravenous administration of anti-PS/PT antibody after subcutaneous histone injection was significantly higher than in those without cutaneous vasculitis. We found LAMP-2 protein overexpression in neutrophils and vascular endothelial cells of the affected blood vessels in rats with cutaneous vasculitis induced by intravenous administration of anti-PS/PT antibody after cutaneous priming by histones. We found typical cutaneous small-vessel vasculitis in the skin of rats given intravenous injection of both anti-PS/PT antibody and anti-LAMP-2 antibody after cutaneous priming by histones. We suggested that the introduction of skin local histones and anti-PS/PT antibody in serum could move LAMP-2 to the cell surface of neutrophils and vascular endothelial cells, and that anti-LAMP-2 antibody could bridge these cells through antigen-specific binding in typical cutaneous small-vessel vasculitis.
我们之前曾报道过,IgA 血管炎和皮肤小动脉炎可能与抗磷脂酰丝氨酸/凝血酶原复合物(抗 PS/PT)抗体和溶酶体相关膜蛋白-2(LAMP-2)的存在有关。在皮下注射组蛋白后静脉注射抗 PS/PT 抗体诱导的大鼠皮肤血管炎组织样本中 LAMP-2mRNA 的拷贝数明显高于无皮肤血管炎的组织样本。我们发现,在皮下注射组蛋白诱导的大鼠皮肤血管炎中,LAMP-2 蛋白在中性粒细胞和受影响血管的血管内皮细胞中过度表达。在皮下注射组蛋白后静脉注射抗 PS/PT 抗体和抗 LAMP-2 抗体的大鼠皮肤中,我们发现了典型的皮肤小血管血管炎。我们认为,皮肤局部组蛋白和血清中的抗 PS/PT 抗体可以将 LAMP-2 转移到中性粒细胞和血管内皮细胞的细胞表面,而抗 LAMP-2 抗体可以通过典型皮肤小血管血管炎中的抗原特异性结合来桥接这些细胞。