Bui Chau M, Vuong Huy G, Le Minh-Khang, Rybski Kristin J, Zengin Hatice B, Tang Haiming, Smoller Bruce R
Department of Pathology and Laboratory Medicine, University of Rochester, Rochester, NY 14642, USA.
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA.
Dermatopathology (Basel). 2023 Dec 21;11(1):1-7. doi: 10.3390/dermatopathology11010001.
Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey-Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism.
Claudin-4是紧密连接的关键组成部分，紧密连接通过在颗粒层形成一个圆周网络，作为细胞旁通路的守门人，在表皮屏障的形成中发挥重要作用。本研究的目的是阐明不同水疱性疾病中Claudin-4的免疫组织化学染色模式。我们收集了35例病例，包括2例黑棘皮病、1例毛囊角化病、3例Grover病、1例棘层松解性棘皮瘤、2例疣状角化不良瘤、11例寻常型天疱疮（PV）（包括6例黏膜PV）和2例落叶型天疱疮。作为对照，我们纳入了5例正常皮肤、5例湿疹和3例大疱性类天疱疮病例。Claudin-4在位于颗粒层的角质形成细胞、毛囊周围的角质形成细胞和附属腺中呈弱至中度表达。此外，在16/22例棘层松解性病例（6例黏膜PV未观察到）和所有3例大疱性类天疱疮的棘层松解和水疱区域周围及内部的破裂角质形成细胞中，Claudin-4表现出中度至强的膜染色。这一发现表明Claudin-4在这些情况下上调，这可能是对破坏的屏障功能的一种代偿反应。这一发现可能有助于揭示水疱性疾病中屏障功能破坏的分子机制，而与具体的潜在疾病机制无关。
