Lin Mong-Shang, Fu Chang-Ling, Olague-Marchan Monica, Hacker Mary K, Zillikens Detlef, Giudice George J, Fairley Janet A
Department of Dermatology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Clin Immunol. 2002 Mar;102(3):310-9. doi: 10.1006/clim.2001.5177.
Linear IgA bullous disease (LABD) is an autoimmune skin disease characterized by subepidermal blisters and IgA autoantibodies directed against the epidermal basement membrane zone (BMZ) of the skin. Various antigens have been identified as targets of IgA autoantibodies including BP180, a type II glycoprotein that spans the BMZ and lamina lucida. Previously, we have identified a subset of LABD patients whose sera contained IgA antibodies against the 16th noncollagenous (NC16A) domain of BP180. NC16A was previously shown to harbor epitopes that are recognized by both autoantibodies and T cells from patients with bullous pemphigoid and herpes gestationis and is thought to be associated with the development of these immunobullous diseases. The aim of this study was to determine whether T lymphocytes from LABD patients with anti-NC16A IgA autoantibodies respond to epitopes in the same region of the BP180 protein. Indeed, of the four LABD patients in our study, all had T cells that specifically proliferated in response to NC16A. Moreover, two subfragments of NC16A were identified as the predominant targets of LABD T cells. Further analysis of T cell lines and clones derived from these patients revealed that these cells express a CD4 memory T cell phenotype and secrete a Th1/Th2 mixed-cytokine profile, characteristics similar to those of T cells in bullous pemphigoid patients. Our data suggest that the BP180 protein, typically the NC16A region, is the common target of both cellular and humoral immune responses in some LABD patients. This information helps to further elucidate the autoimmune mechanisms in this disease.
线状IgA大疱性疾病（LABD）是一种自身免疫性皮肤病，其特征为表皮下水疱以及针对皮肤表皮基底膜带（BMZ）的IgA自身抗体。多种抗原已被确定为IgA自身抗体的靶标，包括BP180，一种跨越BMZ和透明板的II型糖蛋白。此前，我们已鉴定出一部分LABD患者，其血清中含有针对BP180第16个非胶原（NC16A）结构域的IgA抗体。先前研究表明，NC16A含有天疱疮和妊娠疱疹患者自身抗体及T细胞所识别的表位，并且被认为与这些免疫性大疱性疾病的发生有关。本研究的目的是确定具有抗NC16A IgA自身抗体的LABD患者的T淋巴细胞是否对BP180蛋白同一区域的表位产生反应。事实上，在我们研究的4例LABD患者中，所有患者的T细胞均对NC16A产生特异性增殖反应。此外，NC16A的两个亚片段被确定为LABD T细胞的主要靶标。对源自这些患者的T细胞系和克隆的进一步分析显示，这些细胞表达CD4记忆T细胞表型，并分泌Th1/Th2混合细胞因子谱，这些特征与大疱性类天疱疮患者的T细胞相似。我们的数据表明，BP180蛋白，通常是NC16A区域，是一些LABD患者细胞免疫和体液免疫反应的共同靶标。这一信息有助于进一步阐明该疾病的自身免疫机制。
