A case of paraneoplastic pemphigus with antidesmoglein 1 antibodies as determined by immunoblotting
A case of paraneoplastic pemphigus with antidesmoglein 1 antibodies as determined by immunoblotting
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免疫印迹检测伴抗桥粒芯糖蛋白 1 抗体的副肿瘤性天疱疮一例
DOI：
10.1046/j.1365-2133.2000.03433.x
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发表时间：
2000
影响因子：
10.3
通讯作者：
P. Joly
中科院分区：
文献类型：
--
作者：
P. Martel;D. Gilbert;B. Labeille;Jean Kanitakis;P. Joly
副肿瘤性天疱疮（Paraneoplastic pemphigus，PNP）是天疱疮的一个亚类，其临床和组织学特征与多形性红斑、大疱性类天疱疮和扁平苔藓密切相关。PNP自身抗体针对主要由斑蛋白家族的蛋白质组成的抗原复合物：这些是桥粒和半桥粒斑的主要组分。我们首先通过免疫印迹法描述了PNP血清中抗桥粒芯糖蛋白3（Dsg 3）抗体的存在。最近已经证明，致病性抗Dsg 3自身抗体可以通过酶联免疫吸附测定（ELISA）在PNP血清中一致地检测到。奇怪的是，尽管使用ELISA在超过50%的PNP血清中回收了抗桥粒芯糖蛋白1（Dsg 1）抗体，但使用免疫印迹或免疫沉淀测定从未在PNP血清中检测到此类自身抗体。我们描述了一个PNP患者的非典型临床表现，其中循环抗Dsg 1抗体检测免疫印迹。一位70岁男性，有慢性淋巴细胞白血病和前列腺癌病史，表现为全身性苔藓样皮疹。皮肤病变发展为剥脱性红皮病（图1a），伴有下肢非典型靶样病变。患者出现粘膜糜烂和广泛皮肤水疱，Nikolsky征阳性。尽管给予了非肠道抗生素和皮质激素治疗，但他还是死于感染。皮肤水疱的组织学检查显示基底和基底上分裂伴空泡变化和角质形成细胞坏死。直接和间接免疫荧光（IF）显示抗表皮细胞表面抗体，无抗基底膜带抗体。患者的血清在间接IF上染色大鼠膀胱上皮。免疫印迹分析显示IgG抗体针对250-，210-（双联体）和190-kDa分子量的条带，分别对应于桥粒斑蛋白I，envoplakin和桥粒斑蛋白II，和periplakin。此外，患者血清中含有IgG抗体，该抗体可识别与鼠抗Dsg 1单克隆抗体（克隆DG3.10，Progen，Heidelberg，德国）识别的条带共迁移的160-kDa条带（图1b）。令人惊讶的是，迄今为止，从未通过免疫印迹或免疫沉淀在PNP血清中检测到抗Dsg 1抗体，而最近通过使用杆状病毒表达的重组Dsg 1的ELISA测定，在50%的PNP血清中报告了抗Dsg 1抗体。一种可能的解释是，PNP血清，如落叶型天疱疮（PF）血清，可以识别Dsg 1上的构象表位，其在免疫印迹提取过程中变性。PNP抗Dsg 1抗体的致病作用
Sir, Paraneoplastic pemphigus (PNP) is a subset of pemphigus in patients with neoplasia, in which clinical and histological features of pemphigus vulgaris (PV) are variably associated with features of erythema multiforme, bullous pemphigoid and lichen planus. PNP autoantibodies are directed against an antigen complex mainly composed of proteins of the plakin family: these are major components of desmosomal and hemidesmosomal plaques. We first described the presence of antidesmoglein 3 (Dsg3) antibodies in PNP sera by immunoblotting. It has recently been demonstrated that pathogenic anti-Dsg3 autoantibodies can be consistently detected in PNP sera by enzyme-linked immunosorbent assay (ELISA). Curiously, whereas antidesmoglein 1 (Dsg1) antibodies have been recovered in more than 50% of PNP sera using ELISA, such autoantibodies have never been detected in PNP sera using immunoblotting or immunoprecipitation assays. We describe a PNP patient with an atypical clinical presentation in whom circulating anti-Dsg1 antibodies were detected by immunoblotting. A 70-year-old man with a history of chronic lymphoid leukaemia and prostate carcinoma presented with a generalized lichenoid eruption. Cutaneous lesions evolved to an exfoliative erythroderma (Fig. 1a) associated with atypical target-like lesions on the lower limbs. The patient had mucosal erosions and extensive cutaneous blisters with a positive Nikolsky sign. He died of infection despite parenteral antibiotics and corticoid therapy. Histological examination of a cutaneous blister showed basilar and suprabasilar cleavage with vacuolar changes and keratinocyte necrosis. Direct and indirect immunofluorescence (IF) showed antiepidermal cell surface antibodies without antibasement membrane zone antibodies. The patient's serum stained rat bladder epithelium on indirect IF. Immunoblot analysis showed IgG antibodies directed against bands of 250-, 210-(doublet) and 190-kDa molecular weight, corresponding to desmoplakin I, envoplakin and desmoplakin II, and periplakin, respectively. Additionally, the patient's serum contained IgG antibodies that recognized a 160-kDa band comigrating with the band recognized by a murine anti-Dsg1 monoclonal antibody (Clone DG3.10, Progen, Heidelberg, Germany) (Fig. 1b). It is surprising that, to date, anti-Dsg1 antibodies have never been detected in PNP sera by immunoblotting or immunoprecipitation, whereas they have recently been reported in 50% of PNP sera by an ELISA assay using baculovirus-expressed recombinant Dsg1. One possible explanation is that PNP sera, like pemphigus foliaceus (PF) sera, may recognize a conformational epitope on Dsg1 which is denatured during the immunoblotting extraction procedure. The pathogenic effect of PNP anti-Dsg1 antibodies
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影响因子：
6.5
作者：
Frazier, K;Williams, S;Grotendorst, GR
通讯作者：
Grotendorst, GR
红细胞生成性原卟啉症半胱氨酸光保护的双盲研究。
DOI：
--
发表时间：
1994
期刊：
Photodermatology, photoimmunology & photomedicine
影响因子：
--
作者：
Mathews-Roth,MM;Rosner,B;Benfell,K;Roberts,JE
通讯作者：
Roberts,JE
影响因子：
158.5
作者：
FALK, RJ;JENNETTE, JC
通讯作者：
JENNETTE, JC
角蛋白单克隆抗体在人类表皮疾病中的应用：免疫组织化学染色模式的改变。
DOI：
10.1111/1523-1747.ep12518198
发表时间：
1983
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Weiss,RA;Guillet,GY;Freedberg,IM;Farmer,ER;Small,EA;Weiss,MM;Sun,TT
通讯作者：
Sun,TT