Lin M S, Gharia M, Fu C L, Olague-Marchan M, Hacker M, Harman K E, Bhogal B S, Black M M, Diaz L A, Giudice G J
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA.
Clin Immunol. 1999 Sep;92(3):285-92. doi: 10.1006/clim.1999.4756.
Herpes gestationis (HG) is an autoantibody-mediated subepidermal bullous dermatosis associated with pregnancy. The primary target of HG autoantibodies is BP180, a 180-kDa hemidesmosomal glycoprotein. We previously showed that autoantibodies and autoimmune T lymphocytes from HG patients recognize the MCW-1 antigenic site (AA 507-520), which is located in the membrane-proximal noncollagenous domain (NC16A) of BP180. Here, we analyzed the sera of 37 HG patients to further define the sites on BP180 that are targeted by autoantibodies. All of the HG sera, but none of the control sera, were immunoreactive with sec180e, a 120-kDa recombinant protein encompassing the entire BP180 extracellular domain. HG sera depleted of reactivity to NC16A no longer reacted with sec180e, indicating that the major HG-associated epitopes on BP180 are restricted to the NC16A domain. The vast majority of the HG sera (34 of 37) reacted with a 7 amino acid peptide corresponding to the N-terminal half of MCW-1 (MCW-1A). Eleven HG sera (including the 3 that failed to react with MCW-1A) recognized one or more of three antigenic sites located within a 15 amino acid stretch immediately downstream of MCW-1A. In summary, we have identified four major HG-associated epitopes clustered within a 22 amino acid region of the BP180 ectodomain. These findings support the hypothesis that an autoimmune response to the BP180 NC16A domain is a crucial step in the pathogenesis of HG.
妊娠疱疹（HG）是一种与妊娠相关的自身抗体介导的表皮下大疱性皮肤病。HG自身抗体的主要靶标是BP180，一种180 kDa的半桥粒糖蛋白。我们之前表明，HG患者的自身抗体和自身免疫性T淋巴细胞识别MCW-1抗原位点（氨基酸507-520），该位点位于BP180的膜近端非胶原结构域（NC16A）。在此，我们分析了37例HG患者的血清，以进一步确定BP180上被自身抗体靶向的位点。所有HG血清，但对照血清均无，与sec180e有免疫反应，sec180e是一种包含整个BP180细胞外结构域的120 kDa重组蛋白。对NC16A失去反应性的HG血清不再与sec180e反应，表明BP180上主要的HG相关表位局限于NC16A结构域。绝大多数HG血清（37例中的34例）与对应于MCW-1 N端一半的7氨基酸肽（MCW-1A）反应。11例HG血清（包括3例不与MCW-1A反应的血清）识别位于MCW-1A下游紧邻的15氨基酸片段内的三个抗原位点中的一个或多个。总之，我们在BP180胞外结构域的一个22氨基酸区域内确定了四个主要的HG相关表位。这些发现支持了这样的假说，即针对BP180 NC16A结构域的自身免疫反应是HG发病机制中的关键步骤。
