Dermatological survey of HIV seropositive Japanese patients
Dermatological survey of HIV seropositive Japanese patients
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日本 HIV 血清阳性患者的皮肤病学调查
DOI：
10.1046/j.1365-2133.1998.02238.x
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发表时间：
1998
影响因子：
10.3
通讯作者：
Nakajima
中科院分区：
文献类型：
--
作者：
Ishii;Sugita;Nishiyama;Nakajima
SIR、Matsumura等人最近报道了一例全身性萎缩性良性大疱性表皮松解症（GABEB）患者中180 kda大疱性类天疱疮抗原（BP180； XVII型胶原）阳性和阴性细胞的花状分布。此外，作者发现uncein[单克隆抗体（mAb） 19-DEJ-1抗原]在BP180阴性细胞中同时缺失。细胞嵌合体仅在病灶周围皮肤活检中观察到。在临床未受累的患者背部皮肤活检中，BP180和uncein均显示正常的连续模式。作者认为BP180与uncein关系密切，推测其嵌合模式可能是后天获得的，而非遗传的。在最近的一项研究中，我们揭示了GABEB患者的嵌合体是由体细胞前体细胞中的反向突变（即有丝分裂基因转换）引起的。2我们将这种遗传原理称为反向嵌合体，它确实是获得的而不是遗传的。该患者为BP180基因（COL17A1: R1226X/1706delA）的两个截断突变的复合杂合。BP180在细胞中的表达是由母体等位基因突变的逆转引起的。更具体地说，母本突变周围的位点已经被来自父本等位基因的正常序列修复（非互惠杂交或基因转换）。我们的论文没有包含uncein表达的数据。我们现在报告在COL17A1基因突变的患者中，uncein的缺失与BP180的缺失模式相同。如前所述，对GABEB患者临床受影响和未受影响的皮肤冷冻标本进行免疫荧光检测。2 .临床病变皮肤活检标本中，用单克隆抗体1D1和1A8C（由K. Owaribe博士慷慨提供）对BP180进行免疫荧光染色，用单克隆抗体19-DEJ-1对uncein3进行免疫荧光染色均为阴性。然而，在临床未受影响的皮肤中，大约50%的基底细胞中有BP180和uncein染色，尽管强度略有降低（图1）。BP180和uncein在连续切片上的不连续分布模式相似。对两种抗原进行双重免疫染色是不可能的，因为可用的一抗都是在同一物种（即小鼠）中产生的。其他半间粒黏附分子如64整合素、粘连素（HD-1）、BP230、层粘连蛋白-1、层粘连蛋白-5和VII型胶原的染色显示沿表皮基底膜区（EBMZ）呈正常的连续模式（数据未显示）。然而，在缺乏uncein和BP180的细胞中不表达120-kDa线性IgA大疱性皮肤病抗原（lad1抗原）；我们在其他地方详细发表了这一观察结果。COL17A1基因突变继发缺乏uncein和LAD-1表明这些分子与BP180相互作用。Matsumura等人可能观察到了前向嵌合现象，因为在他们的散发性患者中，细胞嵌合现象仅发生在病灶周围（受影响的）皮肤，而未受影响的皮肤则表现出正常的表达模式。然而，为了在EBMZ抗原的嵌合表达与皮肤脆性之间建立临床病理相关性，有必要了解这种突变及其对分子的影响。此外，这些研究强调uncein与laminin-5并不相同。
SIR, Matsumura et al. 1 recently reported a mosaic distribution of 180-kDa bullous pemphigoid antigen (BP180; type XVII collagen) positive and negative cells in a patient with generalized atrophic benign epidermolysis bullosa (GABEB). Moreover, the authors found that uncein [antigen of monoclonal antibody (mAb) 19-DEJ-1] was concomitantly absent in BP180 negative cells. The cellular mosaicism was only observed in biopsies from perilesional skin. In biopsies from clinically uninvolved skin on the back of the patient, both BP180 and uncein showed a normal continuous pattern. The authors concluded that BP180 and uncein are closely related and speculated that the mosaic pattern may be acquired and not inherited. In a recent study, we disclosed that mosaicism in a GABEB patient was caused by a reverse mutation, ie mitotic gene conversion, in somatic precursor cell (s). 2 We called this genetic principle revertant mosaicism, and it is indeed acquired and not inherited. The patient was compound heterozygous for two truncation mutations in the gene of BP180 (COL17A1: R1226X/1706delA). The expression of BP180 in the cells was caused by reversion of the mutation on the maternal allele. More specifically, the site surrounding the maternal mutation had been repaired with the normal sequence from the paternal allele (non-reciprocal crossingover or gene conversion). Our paper did not contain data on the expression of uncein. We now report the absence of uncein in the same pattern as that of BP180 in this patient with mutations in the COL17A1 gene. Immunofluorescence was performed as previously described on frozen specimens of clinically affected and unaffected skin of the patient with GABEB. 2 Immunofluorescence staining with mAbs 1D1 and 1A8C (generously provided by Dr K. Owaribe) against BP180 and with mAb 19-DEJ-1 against uncein3 was negative in biopsy specimens of the clinically affected skin. In the clinically unaffected skin, however, BP180 as well as uncein were stained, although with slightly reduced intensity, in approximately 50% of the basal cells (Fig. 1). The discontinuous distribution pattern of BP180 and uncein was similar in serial sections. Double immunostaining for both antigens was impossible because the available primary antibodies were all generated in the same species, ie the mouse. Staining for other hemidesmosomal adhesion molecules such as 64 integrin, plectin (HD-1), BP230, laminin-1, laminin-5 and type VII collagen showed a normal continuous pattern along the epidermal basement membrane zone (EBMZ)(data not shown). However, 120-kDa linear IgA bullous dermatosis antigen (LAD-1 antigen) was not expressed in cells lacking uncein and BP180; we have published this observation in detail elsewhere. 4 The lack of uncein and LAD-1 secondary to mutations in the COL17A1 gene suggests that these molecules interact with BP180. Matsumura et al. possibly observed forward mosaicism since the cellular mosaicism in their sporadic patient occurred only in perilesional (affected?) skin, whereas the uninvolved skin displayed a normal expression pattern. To make a clinicopathological correlation between mosaic expression of EBMZ antigens and skin fragility, however, it is necessary to know the mutation and its effect on the molecule. Furthermore, these studies underline that uncein is not identical to laminin-5.