Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
J Immunol. 2012 Aug 15;189(4):1535-9. doi: 10.4049/jimmunol.1200842. Epub 2012 Jul 13.
The environmental factors that contribute to the development of autoimmune diseases are largely unknown. Endemic pemphigus foliaceus in humans, known as Fogo Selvagem (FS) in Brazil, is mediated by pathogenic IgG4 autoantibodies against desmoglein 1 (Dsg1). Clusters of FS overlap with those of leishmaniasis, a disease transmitted by sand fly (Lutzomyia longipalpis) bites. In this study, we show that salivary Ags from the sand fly, and specifically the LJM11 salivary protein, are recognized by FS Abs. Anti-Dsg1 monoclonal autoantibodies derived from FS patients also cross-react with LJM11. Mice immunized with LJM11 generate anti-Dsg1 Abs. Thus, insect bites may deliver salivary Ags that initiate a cross-reactive IgG4 Ab response in genetically susceptible individuals and lead to subsequent FS. Our findings establish a clear relationship between an environmental, noninfectious Ag and the development of potentially pathogenic autoantibodies in an autoimmune disease.
导致自身免疫性疾病发展的环境因素在很大程度上是未知的。在人类中，特发性落叶型天疱疮（pemphigus foliaceus），在巴西被称为 Fogo Selvagem（FS），是由针对桥粒芯糖蛋白 1（desmoglein 1，Dsg1）的致病性 IgG4 自身抗体介导的。FS 的发病区域与利什曼病（一种由沙蝇（Lutzomyia longipalpis）叮咬传播的疾病）的发病区域重叠。在这项研究中，我们表明沙蝇唾液中的抗原，特别是 LJM11 唾液蛋白，被 FS 抗体识别。源自 FS 患者的抗 Dsg1 单克隆自身抗体也与 LJM11 发生交叉反应。用 LJM11 免疫的小鼠产生抗 Dsg1 的抗体。因此，昆虫叮咬可能会传递唾液抗原，在遗传易感个体中引发交叉反应性 IgG4 Ab 反应，进而导致随后发生 FS。我们的研究结果在一种环境性、非传染性抗原与自身免疫性疾病中潜在致病性自身抗体的发展之间建立了明确的关系。
