Liu Z, Diaz L A, Giudice G J
Department of Dermatology, Medical College of Wisconsin, Milwaukee 53226.
Dermatology. 1994;189 Suppl 1:34-7. doi: 10.1159/000246925.
An immunodominant and potentially pathogenic epitope associated with bullous pemphigoid (BP) and herpes gestationis (HG) has recently been mapped by our laboratory to a noncollagenous stretch of the extracellular domain of the human BP180 antigen. This antigenic site, designated the MCW-1 epitope, has been shown to be recognized by the majority of BP and HG sera. Interestingly, the MCW-1 epitope is absent from the murine BP180 molecule, and therefore, human autoantibodies directed against this site could not be tested for pathogenicity using the conventional passive transfer mouse model. Alternatively, rabbit antibodies were prepared against recombinant forms of the human MCW-1 epitope and the murine NC16A domain and were tested for pathogenicity by passive transfer experiments. Neonatal mice injected with rabbit antimurine BP180 IgG developed a subepidermal blistering disease that closely mimicked BP and HG at the clinical, histological and immunological levels. Rabbit IgG specific for the human MCW-1 epitope was not pathogenic. These results suggest that the autoantibodies against the MCW-1 epitope of the human BP180 antigen found in BP and HG sera may be relevant in the pathogenesis of blister formation in these patients.
最近，我们实验室已将与大疱性类天疱疮（BP）和妊娠疱疹（HG）相关的一个免疫显性且可能致病的表位定位到人类BP180抗原细胞外结构域的一段非胶原序列上。这个抗原位点，命名为MCW-1表位，已被证明能被大多数BP和HG血清识别。有趣的是，小鼠BP180分子中不存在MCW-1表位，因此，针对该位点的人类自身抗体无法使用传统的被动转移小鼠模型来检测其致病性。作为替代方法，制备了针对人类MCW-1表位和小鼠NC16A结构域重组形式的兔抗体，并通过被动转移实验检测其致病性。注射兔抗小鼠BP180 IgG的新生小鼠发生了一种表皮下疱病，在临床、组织学和免疫学水平上与BP和HG极为相似。对人类MCW-1表位具有特异性的兔IgG没有致病性。这些结果表明，在BP和HG血清中发现的针对人类BP180抗原MCW-1表位的自身抗体可能与这些患者水疱形成的发病机制有关。
