Detection of apoptotic keratinocytes in a case of bullous pemphigoid developed after graft-versus-host disease.
Detection of apoptotic keratinocytes in a case of bullous pemphigoid developed after graft-versus-host disease.
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DOI：
10.2340/00015555-1676
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发表时间：
2014-03
影响因子：
3.6
通讯作者：
K. Yoneda;T. Demitsu;M. Kakurai;T. Narita;K. Nakai;Y. Kubota;N. Ishii;T. Hashimoto
中科院分区：
文献类型：
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作者：
K. Yoneda;T. Demitsu;M. Kakurai;T. Narita;K. Nakai;Y. Kubota;N. Ishii;T. Hashimoto
移植物抗宿主病（GVHD）是造血干细胞移植后常见的并发症。GVHD表现为各种皮肤病变，如斑丘疹、褐色色素沉着和硬皮病（1）。虽然GVHD可能表现为基底细胞空泡变性引起的表皮下水疱，但大疱性类天疱疮（BP）和GVHD的相关性极为罕见（1）。我们在这里报告一例BP开发4个月后异基因骨髓移植（BMT）。有趣的是，组织病理学显示坏死的角化细胞分散在海绵状表皮中，由表皮下水疱屋顶组成。我们进一步研究了坏死角质形成细胞中凋亡细胞和裂解的半胱天冬酶3的存在。一名57岁的日本妇女于2002年11月被诊断为急性髓性白血病。她在接受阿糖胞苷、柔红霉素和吉西他滨化疗后完全缓解。2004年6月，该患者接受了与她的人类白细胞抗原（HLA）相同的姐姐的异基因BMT。尝试使用环孢菌素预防GVHD，并使用甲氨蝶呤进行短期治疗。急性髓细胞白血病完全缓解和100%的供体嵌合体得到证实。2004年10月（BMT后4个月），患者全身出现广泛渗出性水疱（图1a）。新鲜水疱的活检显示表皮下水疱，真皮和大疱中嗜酸性粒细胞和淋巴细胞中度浸润（图1b）。在大疱顶部的表皮中观察到角化不良的角化细胞，伴有海绵状增生（图1b，c）。在不同水疱的水疱顶部也显示出萎缩的角质形成细胞（图1d）。皮肤活检直接免疫荧光显示表皮基底膜区（BMZ）线性免疫球蛋白G（IgG）沉积。正常人皮肤的间接免疫荧光显示循环IgG抗BMZ抗体。1 M氯化钠（NaCl）-分裂皮肤切片的间接免疫荧光显示IgG与分裂表皮侧的反应性（图1 e）。在姐姐中未检测到循环抗BMZ抗体。BP 180和BP 230酶联免疫吸附试验（ELISA）的患者和她的妹妹的血清是阴性的。正常人表皮提取物的免疫印迹分析未检测到针对BP 180或BP 230的IgG抗体。NC 16 a和BP 180 C端结构域重组蛋白的免疫印迹分析均为阴性。开始口服泼尼松龙1 mg/kg/天，导致皮肤病变在1个月内完全消失。6个月后停用口服泼尼松龙。一年后，患者死于白血病脑转移和进行性肾衰竭。为了解角膜上皮细胞坏死的特点，
Graft-versus-host disease (GVHD) is a frequent complication following haematopoietic stem cell trans-plantation. GVHD reveals various skin lesions, such as maculo-papular rash, brownish pigmentation, and sclero-derma (1). Although GVHD may present subepidermal blisters caused by vacuolar degeneration of basal cells, the association of bullous pemphigoid (BP) and GVHD is extremely rare (1). We report here a case of BP that developed 4 months after allogeneic bone marrow transplantation (BMT). Interestingly, histopathology revealed necrotic keratino-cytes scattered in the spongiotic epidermis, composed of subepidermal blister roof. We further investigated the necrotic keratinocytes for the presence of apoptotic cells and cleaved caspase 3. A 57-year-old Japanese woman was diagnosed with acute mye-logenous leukaemia in November 2002. She achieved complete remission after chemotherapy with cytarabine, daunorubicin and gemcitabine. In June 2004, the patient underwent allogeneic BMT from her human leukocyte antigen (HLA)-identical older sister. GVHD prophylaxis was attempted with cyclosporine and short-term treatment with methotrexate. Complete remission of the acute myelogenous leukaemia and 100% donor chimerism were confirmed. In October 2004 (4 months after BMT), extensive exudative erythemas with blisters appeared over the patient's entire body surface (Fig. 1a). A biopsy from a fresh vesicle showed sub-epidermal blistering and moderate infiltration of both eosinophils and lymphocytes in both the dermis and the bulla (Fig. 1b). Dys-keratotic keratinocytes were observed in the epidermis at the roof of the bulla with spongiosis (Fig. 1b, c). Shrunken keratinocytes were also demonstrated in the blister roof of different blisters (Fig. 1d). Direct immunofluorescence of skin biopsy showed linear immunoglobulin G (IgG) deposition in the epidermal basement membrane zone (BMZ). Indirect immunofluorescence of normal human skin revealed circulating IgG anti-BMZ antibodies. Indirect immunofluorescence of 1 M sodium chloride (NaCl)-split skin sections showed IgG reactivity with the epidermal side of the split (Fig. 1e). No circulating anti-BMZ antibodies were detected in the older sister. BP180 and BP230 enzyme-linked immunosorbent assays (ELISAs) of the sera from the patient and her sister were negative. Immunoblot analysis of normal human epidermal extracts did not detect IgG antibodies to either BP180 or BP230. Immu-noblot analysis of recombinant proteins of NC16a and C-terminal domains of BP180 showed negative results. Oral prednisolone, 1 mg/kg/day, was started, leading to complete disappearance of the skin lesions within one month. Oral prednisolone was discontinued 6 months later. One year later, the patient died from brain metastasis of leukaemia and progressive renal failure. In order to characterize the necrotic kera-tinocytes in …