Zhou S, Ferguson D J, Allen J, Wojnarowska F
Department of Dermatology, Oxford Radcliffe Hospital, Oxford OX3 7LJ, U.K.
Br J Dermatol. 1998 Oct;139(4):591-7. doi: 10.1046/j.1365-2133.1998.02453.x.
Linear IgA disease (LAD) of adults and children is a dapsone-responsive, autoimmune subepidermal blistering disease characterized by linear IgA deposits at the basement membrane zone (BMZ) of the skin and mucosa. Circulating IgA antibodies to BMZ components are often present. In this study we investigated the ultrastructural localization of the antigens and autoantibodies in six patients with LAD (five adults and one child). Using a direct postembedding immunogold electron microscopy (EM) technique, three different patterns of IgA antibody deposition were seen in the skin of four patients with LAD. The IgA deposits localized within the uppermost part of the lamina lucida and to the basal surface of the hemidesmosome in two patients, to the lamina lucida in one, and to the lamina densa in the fourth patient. Using an indirect immunogold EM technique and serum or purified blister fluid from two additional LAD patients, we showed that the serum autoantibodies of one patient bound to the hemidesmosome of the BMZ, while the autoantibodies in the blister fluid of the other patient bound to the lamina densa and sublamina densa including the anchoring fibrils in a labelling pattern similar to that of the monoclonal antibody (LH7.2) to collagen VII. All the autoantibodies binding to the hemidesmosome or lamina lucida recognized a protein in epidermal extracts of molecular weight 180 kDa or its breakdown product of 97 kDa, 200 kDa or 230 kDa. The antibodies binding to the lamina densa recognized proteins of 180 and 285 kDa. The antibodies that bound to the lamina densa and anchoring fibrils recognized collagen VII. In this immunogold EM study we have shown four patterns of IgA labelling in six patients with LAD, associated with five different antigens as recognized by immunoblotting. These results, together with our previous immunofluorescence and immunoblotting findings add support to the contention that LAD is a heterogeneous disease as regards both the target antigens and epitopes.
成人和儿童线状IgA疾病（LAD）是一种对氨苯砜有反应的自身免疫性表皮下大疱性疾病，其特征是在皮肤和黏膜的基底膜带（BMZ）处有线状IgA沉积。通常存在针对BMZ成分的循环IgA抗体。在本研究中，我们调查了6例LAD患者（5例成人和1例儿童）中抗原和自身抗体的超微结构定位。使用直接包埋后免疫金电子显微镜（EM）技术，在4例LAD患者的皮肤中观察到三种不同模式的IgA抗体沉积。在两名患者中，IgA沉积定位于透明板的最上部和半桥粒的基底表面，在一名患者中定位于透明板，在第四名患者中定位于致密板。使用间接免疫金EM技术以及另外两名LAD患者的血清或纯化疱液，我们发现一名患者的血清自身抗体与BMZ的半桥粒结合，而另一名患者疱液中的自身抗体与致密板和致密板下包括锚定原纤维的区域结合，其标记模式类似于抗胶原VII单克隆抗体（LH7.2）。所有与半桥粒或透明板结合的自身抗体识别表皮提取物中分子量为180 kDa的蛋白质或其97 kDa、200 kDa或230 kDa的降解产物。与致密板结合的抗体识别180 kDa和285 kDa的蛋白质。与致密板和锚定原纤维结合的抗体识别胶原VII。在这项免疫金EM研究中，我们在6例LAD患者中显示了四种IgA标记模式，与免疫印迹识别的五种不同抗原相关。这些结果，连同我们之前的免疫荧光和免疫印迹结果，支持了LAD在靶抗原和表位方面是一种异质性疾病的观点。
