Chan L S, Fine J D, Briggaman R A, Woodley D T, Hammerberg C, Drugge R J, Cooper K D
Department of Dermatology, University of Michigan School of Medicine, Ann Arbor.
J Invest Dermatol. 1993 Sep;101(3):262-7. doi: 10.1111/1523-1747.ep12365189.
Certain skin basement membrane components, such as bullous pemphigoid antigens and epidermolysis bullosa acquisita antigen, were discovered as a result of an autoimmune reaction. In this report, we describe a unique lamina lucida determinant associated with a novel immune-mediated subepidermal bullous dermatosis. This unique bullous dermatosis resembled severe toxic epidermal necrolysis clinically. The histologic findings resemble dermatitis herpetiformis. Direct immunofluorescence microscopy detected linear immunoglobulin G (IgG) and C3 deposition at the cutaneous basement membrane zone of lesional and perilesional skin. Direct and indirect immunoelectron microscopy localized the IgG deposits to the lowest portion of the lamina lucida. The patient's autoantibodies, belonging to the IgG1 subclass, labeled basement membrane zone of normal intact human skin, oral mucosa, and conjunctiva, and localized to the dermal side of salt-split normal adult and neonatal human skin, but failed to react with human fetal skin up to 142 gestational days. The patient's autoantibodies failed to react with bullous pemphigoid antigens or epidermolysis bullosa acquisita antigen (type VII collagen) by immunoblotting. Instead, the patient's autoantibodies unequivocally labeled a 105-kilodalton (kD) protein in cellular extracts and conditioned media of human cultured keratinocytes and dermal fibroblasts. The titer of the patient's antibody against the cutaneous basement membrane zone and the intensity of the antibody reactivity against the 105-kD protein paralleled the patient's disease activity. Thus, this 105-kD lower lamina lucida protein represents a novel autoantigen and this patient's disease represents a novel autoantigen and this patient's disease represents a deep lamina lucida pemphigoid, distinguishable from all other known autoimmune bullous dermatoses.
某些皮肤基底膜成分，如大疱性类天疱疮抗原和获得性大疱性表皮松解症抗原，是自身免疫反应的结果。在本报告中，我们描述了一种与新型免疫介导的表皮下大疱性皮肤病相关的独特透明层决定簇。这种独特的大疱性皮肤病在临床上类似于严重中毒性表皮坏死松解症。组织学表现类似于疱疹样皮炎。直接免疫荧光显微镜检查在皮损及皮损周围皮肤的皮肤基底膜区检测到线性免疫球蛋白G（IgG）和C3沉积。直接和间接免疫电子显微镜检查将IgG沉积物定位在透明层的最下部。患者的自身抗体属于IgG1亚类，标记正常完整的人皮肤、口腔黏膜和结膜的基底膜区，并定位于盐裂正常成人和新生儿皮肤的真皮侧，但与妊娠142天以内的人胎儿皮肤无反应。通过免疫印迹法，患者的自身抗体与大疱性类天疱疮抗原或获得性大疱性表皮松解症抗原（VII型胶原）无反应。相反，患者的自身抗体在人培养角质形成细胞和真皮成纤维细胞的细胞提取物和条件培养基中明确标记出一种105千道尔顿（kD）的蛋白质。患者针对皮肤基底膜区的抗体滴度以及针对105-kD蛋白质的抗体反应强度与患者的疾病活动度平行。因此，这种105-kD的透明层下部蛋白质代表一种新型自身抗原，该患者的疾病代表一种新型自身抗原，且该患者的疾病代表一种深部透明层类天疱疮，可与所有其他已知的自身免疫性大疱性皮肤病相区分。
