Department of Dermatology, University of Luebeck, Luebeck, Germany.
Department of Dermatology, Kurume University School of Medicine, Kurume, Japan.
J Am Acad Dermatol. 2014 Jul;71(1):185-91. doi: 10.1016/j.jaad.2014.02.036. Epub 2014 Apr 24.
Anti-p200 pemphigoid is a rare subepidermal blistering skin disease. Patients' autoantibodies label the dermal side of 1 mol/L NaCl-split human skin by indirect immunofluorescence microscopy and recognize a 200-kd protein by immunoblotting of human dermal extract. Clinically, anti-p200 pemphigoid is characterized by tense blisters and vesicles, erosions, and urticarial plaques, closely resembling bullous pemphigoid and the inflammatory variant of epidermolysis bullosa acquisita. Recently, 90% of anti-p200 pemphigoid sera were shown to recognize laminin γ1. The C-terminus of laminin γ1 was identified as an immunodominant region and in its recombinant form was used by immunoblotting and enzyme-linked immunosorbent assay for the serologic diagnosis of this disease. Subsequent ex vivo and in vivo studies were, however, unable to show pathogenic activity of antilaminin γ1 antibodies. Both patients' sera and sera depleted from antilaminin γ1 antibodies induced subepidermal splitting in an ex vivo model of autoantibody-mediated leukocyte-dependent neutrophil activation. Antilaminin γ1 antibodies appear to be useful biomarkers that will further facilitate the diagnosis of anti-p200 pemphigoid. The true identity of the pathogenetically relevant autoantigen of this disease, which may either be a yet unknown isoform of laminin γ1 or even another 200-kd protein of the dermoepidermal junction, still needs to be elucidated.
抗 p200 天疱疮是一种罕见的表皮下水疱性皮肤病。患者的自身抗体通过间接免疫荧光显微镜标记 1mol/L NaCl 分离的人皮肤的真皮侧，并通过免疫印迹分析人真皮提取物识别 200kD 蛋白。临床上，抗 p200 天疱疮的特征是紧张性水疱和大疱、糜烂和荨麻疹样斑块，与大疱性类天疱疮和获得性大疱性表皮松解症的炎症变异型非常相似。最近，90%的抗 p200 天疱疮血清被证明识别层粘连蛋白 γ1。层粘连蛋白 γ1 的 C 末端被确定为免疫优势区，其重组形式用于免疫印迹和酶联免疫吸附试验来诊断这种疾病。然而，随后的体外和体内研究未能显示抗层粘连蛋白 γ1 抗体的致病性活性。在体外抗体介导的白细胞依赖性中性粒细胞激活模型中，患者血清和从抗层粘连蛋白 γ1 抗体中耗尽的血清都能诱导表皮下水疱分离。抗层粘连蛋白 γ1 抗体似乎是有用的生物标志物，将进一步促进抗 p200 天疱疮的诊断。这种疾病的潜在相关自身抗原的真实身份，可能是尚未被发现的层粘连蛋白 γ1 同种型，甚至是真皮表皮连接的另一个 200kD 蛋白，仍需要阐明。
