Cirillo Nicola, Gombos Fernando, Lanza Alessandro
Regional Center on Craniofacial Malformations-MRI, Department of Ondontostomatology, II University of Naples, Naples, Italy.
Immunology. 2007 Jul;121(3):377-82. doi: 10.1111/j.1365-2567.2007.02585.x. Epub 2007 Mar 26.
Pemphigus vulgaris (PV) is considered to be an autoimmune disease affecting skin and mucous membranes. Traditionally, PV autoantibodies are thought to recognize antigens located in the intercellular substance (ICS) of keratinocytes; antigens represented mainly by the desmosomal cadherin desmoglein 3 (Dsg3). Accordingly, titres of anti-ICS and anti-Dsg3 immunoglobulin G (IgG) are considered to be major laboratory criteria when making a diagnosis of PV. In this paper, we demonstrated for the first time that PV IgG bind antigen(s) expressed on the surface of peripheral blood mononuclear cells (PBMC), as revealed by immunofluorescence studies. This novel autoantigen is immunoprecipitated by PV IgG as a 130 000 molecular weight protein. However, Western blot analysis of the immunocomplexes failed to show reactivity with anti-Dsg3 monoclonal and polyclonal antibodies. Taken together, our data provide strong evidence that PV autoimmunity targets a 130 000 antigen other than Dsg3 on PBMC. This shifting from epidermis to blood cells may open new perspectives for a better understanding of pemphigus autoimmunity and more rational approaches to its treatment.
寻常型天疱疮(PV)被认为是一种影响皮肤和黏膜的自身免疫性疾病。传统上,PV自身抗体被认为可识别位于角质形成细胞细胞间质(ICS)中的抗原;这些抗原主要由桥粒钙黏蛋白桥粒芯糖蛋白3(Dsg3)代表。因此,抗ICS和抗Dsg3免疫球蛋白G(IgG)的滴度被认为是诊断PV时的主要实验室标准。在本文中,我们首次证明PV IgG可结合外周血单个核细胞(PBMC)表面表达的抗原,免疫荧光研究揭示了这一点。这种新的自身抗原被PV IgG免疫沉淀为一种分子量为130 000的蛋白质。然而,免疫复合物的蛋白质印迹分析未能显示与抗Dsg3单克隆和多克隆抗体发生反应。综上所述,我们的数据提供了强有力的证据,表明PV自身免疫靶向PBMC上除Dsg3之外的一种130 000抗原。这种从表皮向血细胞的转变可能为更好地理解天疱疮自身免疫及更合理的治疗方法开辟新的前景。