Arase Noriko, Sasaoka Yusuke, Narita Jun, Kiyohara Eiji, Hashimoto Kazuhisa, Shinzaki Shinichiro, Nojima Satoshi, Takagi Junichi, Fujimoto Manabu
Department of Dermatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Department of Pediatrics, Osaka University Graduate School of Medicine, Osaka, Japan.
J Eur Acad Dermatol Venereol. 2024 Feb;38(2):404-412. doi: 10.1111/jdv.19582. Epub 2023 Nov 20.
Anti-α6β4 integrin autoantibodies can be observed in some patients with mucous membrane pemphigoid. We have previously identified anti-α6β4 integrin extracellular domain autoantibodies together with anti-BP180 NC16A antibodies in a patient with DPP-4 inhibitor-induced bullous pemphigoid. However, the significance and impact of anti-α6β4 integrin antibodies are unknown.
To characterize anti-α6β4 integrin extracellular domain autoantibodies in pemphigoid patients, to determine whether these antibodies inhibit laminin-α6β4 integrin binding and to observe their systemic effects.
Anti-α6β4 integrin autoantibodies were analysed by staining cells expressing the extracellular region of α6β4 integrin with sera from 20 patients with pemphigoid. The anti-α6β4 integrin autoantibodies were characterized using different transfectants. The binding of laminins to α6β4 integrin was studied using cells expressing the activated conformation of α6β4 integrin and the inhibitory effect of the autoantibodies on the binding of laminins to α6β4 integrin was tested. Trends in antibody titres and clinical symptoms were quantified and analysed.
IgG autoantibodies against the extracellular domain of anti-α6β4 integrin were found in some patients with pemphigoid. Laminin binding to α6β4 integrin was observed in the active conformation of α6β4 integrin, and serum from a patient with a high titre of anti-α6β4 integrin antibodies inhibited the binding of both laminin-511 and laminin-332 to α6β4 integrin. α6β4 integrin is expressed on the basement membrane of both skin and small intestine, and exfoliation was observed in the patient's epidermis and small intestinal epithelium. A reduction in the titre of the anti-α6β4 integrin antibody was associated with improvement in both skin and gastrointestinal symptoms.
This study demonstrated the presence of anti-α6β4 integrin extracellular domain-specific autoantibodies in some patients with pemphigoid. In addition, these autoantibodies showed inhibitory activity on α6β4 integrin-laminin binding. Anti-α6β4 integrin antibodies can affect the gastrointestinal tract as well as the skin and oral mucosa.
在一些黏膜类天疱疮患者中可观察到抗α6β4整合素自身抗体。我们之前在一名患有二肽基肽酶-4抑制剂诱导的大疱性类天疱疮患者中，发现了抗α6β4整合素细胞外结构域自身抗体以及抗BP180 NC16A抗体。然而，抗α6β4整合素抗体的意义和影响尚不清楚。
对类天疱疮患者的抗α6β4整合素细胞外结构域自身抗体进行特征分析，确定这些抗体是否抑制层粘连蛋白-α6β4整合素结合，并观察其全身效应。
用20例类天疱疮患者的血清对表达α6β4整合素细胞外区域的细胞进行染色，分析抗α6β4整合素自身抗体。使用不同的转染细胞对抗α6β4整合素自身抗体进行特征分析。利用表达活化构象的α6β4整合素的细胞研究层粘连蛋白与α6β4整合素的结合情况，并检测自身抗体对层粘连蛋白与α6β4整合素结合的抑制作用。对抗体滴度和临床症状的变化趋势进行量化和分析。
在一些类天疱疮患者中发现了针对抗α6β4整合素细胞外结构域的IgG自身抗体。在α6β4整合素的活化构象中观察到层粘连蛋白与α6β4整合素的结合，一名抗α6β4整合素抗体滴度高的患者的血清抑制了层粘连蛋白-511和层粘连蛋白-332与α6β4整合素的结合。α6β4整合素在皮肤和小肠的基底膜上均有表达，该患者的表皮和小肠上皮出现了剥脱现象。抗α6β4整合素抗体滴度的降低与皮肤和胃肠道症状的改善相关。
本研究证明了在一些类天疱疮患者中存在抗α6β4整合素细胞外结构域特异性自身抗体。此外，这些自身抗体对α6β4整合素-层粘连蛋白结合具有抑制活性。抗α6β4整合素抗体可影响胃肠道以及皮肤和口腔黏膜。
