Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany.
Lübeck Institute of Experimental Dermatology, University of Lübeck, Lübeck, Germany; Department of Dermatology, Allergology and Venerology, University of Lübeck, Lübeck, Germany.
J Am Acad Dermatol. 2024 Apr;90(4):790-797. doi: 10.1016/j.jaad.2023.11.014. Epub 2023 Nov 20.
Anti-p200 pemphigoid is a subepidermal autoimmune blistering disease (AIBD) characterized by autoantibodies against a 200 kDa protein. Laminin γ1 has been described as target antigen in 70% to 90% of patients. No diagnostic assay is widely available for anti-p200 pemphigoid, which might be due to the unclear pathogenic relevance of anti-laminin γ1 autoantibodies.
To identify a target antigen with higher clinical and diagnostic relevance.
Immunoprecipitation, mass spectrometry, and immunoblotting were employed for analysis of skin extracts and sera of patients with anti-p200 pemphigoid (n = 60), other AIBD (n = 33), and healthy blood donors (n = 29). To localize the new antigen in skin, cultured keratinocytes and fibroblasts, quantitative real-time polymerase chain reaction and immunofluorescence microscopy were performed.
Laminin β4 was identified as target antigen of anti-p200 pemphigoid in all analyzed patients. It was located at the level of the basement membrane zone of the skin with predominant expression in keratinocytes.
A higher number of sera needs to be tested to verify that laminin β4 is the diagnostically relevant antigen of anti-p200 pemphigoid.
The identification of laminin β4 as an additional target antigen in anti-p200 pemphigoid will allow its differentiation from other AIBD and as such, improve the management of these rare disorders.
抗 p200 天疱疮是一种表皮下自身免疫性水疱病（AIBD），其特征是针对 200kDa 蛋白的自身抗体。层粘连蛋白 γ1 已在 70%至 90%的患者中被描述为靶抗原。目前尚无广泛可用的抗 p200 天疱疮诊断检测方法，这可能是由于抗层粘连蛋白 γ1 自身抗体的发病机制相关性尚不清楚。
确定具有更高临床和诊断相关性的靶抗原。
采用免疫沉淀、质谱和免疫印迹分析抗 p200 天疱疮（n=60）、其他 AIBD（n=33）和健康献血者（n=29）的皮肤提取物和血清。为了在皮肤中定位新抗原，进行了培养的角质形成细胞和成纤维细胞的定量实时聚合酶链反应和免疫荧光显微镜检查。
在所有分析的患者中，层粘连蛋白 β4 被鉴定为抗 p200 天疱疮的靶抗原。它位于皮肤基底膜带水平，在角质形成细胞中表达为主。
需要测试更多的血清来验证层粘连蛋白 β4 是抗 p200 天疱疮的诊断相关抗原。
将层粘连蛋白 β4 鉴定为抗 p200 天疱疮的另一个靶抗原，将使其与其他 AIBD 区分开来，从而改善这些罕见疾病的管理。
