Abstract：
Dear Editor, Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by erosive mucosal lesions mainly on the oral and ocular mucosae (1). We report a case of oral and ocular anti-BP180-type MMP with variable IgG and IgA reactivities and underlying dementia. An 84-year-old Japanese man presented with a 4-year history of erosions in the oral cavity and on the conjunctivae, with progressive vision impairment. The medical history included benign prostatic hyperplasia, cataract, sinusitis, and dementia. Physical examination revealed erosions and white atrophic scars along the gingival mucosa and on the hard palate (Figure 1, a, b). Conjunctival inflammation and corneal scarring were also observed only on the left eye (Figure 1, c, d). No lesions were observed on the skin or on any other mucosae. A skin biopsy from the patient\'s oral mucosa showed lymphocytic infiltration in the superficial dermis without apparent subepithelial blister. Direct immunofluorescence showed linear depositions of IgG, IgA, and C3 at the epithelial basement membrane zone (Figure 1, e-g). Circulating IgG and IgA autoantibodies were not detected by indirect immunofluorescence of normal human skin, while circulating IgA, but not IgG, autoantibodies were bound to the epidermal side of 1M NaCl-split normal human skin at 1:10 serum dilution (Figure 1, h, i). Commercially available IgG enzyme-linked immunosorbent assays (ELISAs) of BP180 NC16a domain, BP230, and type VII collagen (MBL, Nagoya, Japan) showed negative results. IgG and IgA immunoblotting analyses of six different antigen sources, including BP180 C-terminal domain recombinant protein, were all negative. However, ELISA of full-length BP180 was slightly positive for IgG antibodies (index = 5.79; cut-off <4.64). Immunoblotting analysis of full-length BP180 was negative for both IgG and IgA antibodies (Figure 1, j, k). Immunoblotting analysis of hemidesmosome-rich fraction was negative for both IgG and IgA antibodies to integrin β4 (Figure 1, l). Based mainly on the clinical and immunological findings, we established a diagnosis of MMP with IgG and IgA autoantibodies, likely reactive with BP180. Because the patient refused systemic treatments, we prescribed a mouth rinse sodium gualenate hydrate and eyedrops of fluorometholone and purified sodium hyaluronate, which did not improve the oral and ocular mucosal symptoms during the 8 month follow-up period (Figure 1, m, n). Both IgG and IgA autoantibodies in anti-BP180-type MMP tend to react with the C-terminal domain of BP180 (2), and IgG autoantibodies in 39.7% of MMP patients reactive with the epidermal side of split skin were reported to be positive with BP180 C-terminal domain (3). The full-length BP180 ELISA shows excellent sensitivity for diagnosing BP180-type MMP (4). The different IgG and IgA reactivities among various methods used in the present study may be attributed either to different methodologies (i.e., immunoblotting or ELISA) or to the different substrates, since BP180-type MMP targets various regions of BP180, including the NC16a domain, the C-terminal domain, and the intracytoplasmic region (5). Precise diagnosis for MMP by various immunological methods is critical, because urgent and extensive treatments are necessary for the ocular and laryngeal lesions, which may result in loss of eyesight and airway obstruction, respectively. Acknowledgments: We express our gratitude to Ms. Mako Mine and Dr. Daisuke Hayashi, Department of Dermatology, Osaka City University Graduate School of Medicine in Osaka, Japan for the HD-rich fraction immunoblotting analysis, and Dr. Yoshiaki Hirako, Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya, Aichi, Japan for the preparation of the HD-rich fraction sample. This work was supported by JSPS KAKENHI Grant Number JP20k08684 and the Hirosaki University Research Support System.
摘要：
亲爱的编辑，粘膜类天疱疮（MMP）是一种自身免疫性起泡疾病，其特征是主要在口腔和眼粘膜上的糜烂性粘膜病变（1）。我们报告了一例口服和眼部抗BP180型MMP，具有可变的IgG和IgA反应性和潜在的痴呆。一名84岁的日本男子在口腔和结膜上有4年的糜烂史，进行性视力障碍。病史包括良性前列腺增生，白内障,鼻窦炎,和痴呆症。体格检查发现沿着牙龈粘膜和硬腭的糜烂和白色萎缩性疤痕（图1，a，b).结膜炎症和角膜瘢痕也仅在左眼观察到（图1，c，d).在皮肤或任何其他粘膜上未观察到病变。患者口腔粘膜皮肤活检显示真皮浅层淋巴细胞浸润，无明显上皮下水疱。直接免疫荧光显示IgG的线性沉积，IgA,和C3在上皮基底膜区（图1，e-g）。通过正常人皮肤的间接免疫荧光未检测到循环IgG和IgA自身抗体，而循环的IgA,但不是IgG，自身抗体以1：10的血清稀释度与1MNaCl分裂的正常人皮肤的表皮结合（图1，h，i).BP180NC16a结构域的市售IgG酶联免疫吸附测定（ELISA），BP230和VII型胶原蛋白（MBL，名古屋,日本）显示负面结果。6种不同抗原来源的IgG和IgA免疫印迹分析,包括BP180C端结构域重组蛋白，都是负面的。然而,全长BP180的ELISA对IgG抗体略呈阳性(指数=5.79;截止值<4.64)。全长BP180的免疫印迹分析对IgG和IgA抗体均为阴性（图1，j，k).富含半网结小体的级分的免疫印迹分析对于针对整联蛋白β4的IgG和IgA抗体均为阴性(图1,1)。主要基于临床和免疫学发现，我们用IgG和IgA自身抗体建立了MMP的诊断，可能与BP180反应。因为病人拒绝全身治疗,我们规定了漱口水瓜伦酸钠水合物和氟米龙和纯化透明质酸钠的滴眼液，在8个月的随访期间，没有改善口腔和眼部粘膜症状（图1，m，n).抗BP180型MMP中的IgG和IgA自身抗体都倾向于与BP180的C末端结构域反应（2），据报道，39.7％的与皮肤分裂的表皮侧反应的MMP患者的IgG自身抗体对BP180C末端结构域呈阳性（3）。全长BP180ELISA对诊断BP180型MMP显示出极好的敏感性(4)。本研究中使用的各种方法中不同的IgG和IgA反应性可能归因于不同的方法(即，免疫印迹或ELISA）或对不同的底物，由于BP180型MMP靶向BP180的各个区域，包括NC16a结构域，C端结构域，和胞质内区域(5)。通过各种免疫学方法对MMP的精确诊断至关重要，因为眼部和喉部病变需要紧急和广泛的治疗，这可能会导致视力丧失和气道阻塞，分别。致谢:我们向MakoMine女士和林大助博士表示感谢,皮肤科,大阪城市大学医学院，日本用于富含HD的部分免疫印迹分析，还有YoshiakiHirako博士,生物科学司,科学研究生院,名古屋大学,名古屋,爱知,日本用于制备富含HD的级分样品。这项工作得到了JSPSKAKENHI资助号JP20k08684和Hirosaki大学研究支持系统的支持。
