自身免疫性大疱性皮肤病的实验室诊断进展

doi:10.16150/j.1671-2870.2023.03.16

摘要/Abstract

摘要：

自身免疫性大疱性皮肤病（autoimmune bullous dermatoses，AIBD）与针对皮肤及黏膜组织中结构蛋白的自身抗体相关。天疱疮疾病中的自身抗体主要针对桥粒的组成部分，而类天疱疮疾病中的自身抗体主要针对真表皮连接的结构蛋白。这两类疾病的治疗方法不同，因此需要依靠实验室诊断予以鉴别。传统实验室诊断方法包括直接免疫荧光（direct immunofluorescence，DIF）、间接免疫荧光（indirect immunofluorescence，IIF）、酶联免疫吸附试验（enzyme-inked immunosorbent assay，ELISA) 和免疫印迹（immunoblotting，IBT）。近年来，不断有新型实验室技术出现。生物芯片技术简化了IIF的判读，成本较低且高效，对桥粒芯糖蛋白（Dsg3）和大疱性类天疱疮抗原180（BP180）的检出率分别高达97%~100%和94%；EUROTide^TM 孵育技术比传统DIF方法灵敏度和特异度更高，背景荧光更少；MESACUP anti-Skin profile TEST能同时检测多种抗体，对Dsg1和Dsg3的检测特异度可达100%；侧向流动免疫层析技术（lateral flow immunoassay，LFIA）可用于快速定性检测，能肉眼观察结果；化学发光酶免疫技术与ELISA相比符合率可达到94%~99%，且检测时间短、自动化程度高；荧光叠加抗原定位-激光扫描共焦显微镜技术（fluorescence overlay antigen mapping using laser-scanning confocal microscopy，FOAM-LSCM）能够一次性对皮肤基底膜带的不同成分进行区别染色，比传统手工DIF法效率更高，且有助于诊断在传统方法下难以与大疱性类天疱疮或获得性大疱性表皮松解症区分的AIBD。实验室诊断技术对AIBD的治疗和预后有着重要作用，本文基于传统实验室方法，比较并探讨了新技术在AIBD诊断中的应用价值。

关键词: 自身免疫性大疱性皮肤病, 直接免疫荧光, 大疱性类天疱疮抗原180, 实验室

Abstract:

Autoimmune bullous dermatoses (AIBD) are associated with autoantibodies against structural components in the skin and mucous membranes. Pemphigus diseases are associated with autoantibodies against the components of desmoglein, while pemphigoid diseases are associated with autoantibodies targeting the structural proteins of the dermal‐epidermal junction. Depending on the components targeted by the autoimmune system, treatments for the two types of diseases are different, so laboratory diagnosis is required for identification. Traditional laboratory diagnosis methods include direct immunofluorescence (DIF), indirect immunofluorescence (IIF), enzyme‐linked immunosorbent assay (ELISA) and immunoblotting (IBT). In recent years, new technologies have emerged. The low‐cost and efficient BIOCHIP technology simplifies the interpretation of IIF, and detection rates of Dsg3 and BP180 are as high as 97%-100% and 94% respectively. EUROTide^TM technology is more sensitive and specific than traditional DIF methods, with less background fluorescence. MESACUP anti-Skin profile TEST (ASPT) can detect multiple antibodies simultaneously, and the detection specificity for Dsg1 and Dsg3 reaches 100%. Lateral flow immunoassay (LFIA) can be used for rapid qualitative testing and results can be checked visually. Chemiluminescence enzyme immunoassay is highly automated and efficient, with 94%-99% compliance rate compared with ELISA. Fluorescence overlay antigen mapping using laser‐scanning confocal microscopy (FOAM‐LSCM) can differentially stain different components of the skin basement membrane zone by one‐ime, which is more efficient than the traditional manual DIF method, and is useful for diagnosing the AIBD that is difficult to differentiate from bullous pemphigoid or acquired epidermolysis bullosa under traditional methods. Laboratory diagnostic technology plays an important role in the treatment and prognosis of AIBD. Based on traditional laboratory methods, this article compares and discusses the value of new technologies in the diagnosis of AIBD.

Key words: Autoimmune bullous dermatoses, Direct immunofluorescence assay, Bullous pemphigoid antigen 180, Laboratory

中图分类号:

R758.66

乌心怡, 潘萌, 朱海琴. 自身免疫性大疱性皮肤病的实验室诊断进展[J]. 诊断学理论与实践, 2023, 22(03): 306-310.

WU Xinyi, PAN Meng, ZHUN Haiqin. Advances in laboratory diagnosis of autoimmune bullous dermatoses[J]. Journal of Diagnostics Concepts & Practice, 2023, 22(03): 306-310.

图/表 2

参考文献 34

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表皮内水疱病	桥粒黏附结构
寻常型天疱疮	Dsg3，Dsg1
落叶型天疱疮	Dsg1
红斑型天疱疮	Dsg1
增殖型天疱疮	Dsg3，Dsg1，Dsc3
副肿瘤型天疱疮	Dsg3，Dsg1，Dsc1，Dsc2，Dsc3，
	斑蛋白家族，α₂-巨球样蛋白1，
	BP230，BP180
IgA天疱疮	Dsg1，Dsg3，Dsc1，Dsc2，Dsc3
疱疹样天疱疮	Dsg1，Dsg3，Dsc1，Dsc3

表皮下水疱病	真表皮连接成分
大疱性类天疱疮	BP180，BP230
妊娠性类天疱疮	BP180
线状IgA大疱性皮病	LAD-1，LABD-97，BP180，BP230，
	VII型胶原
黏膜类天疱疮	BP180，BP230，层粘连蛋白332，
	α6β4整合素，Ⅶ型胶原
抗p200类天疱疮	p200
获得性大疱性表皮松解症	Ⅶ型胶原
疱疹样皮炎	谷氨酰胺转移酶
扁平苔藓类天疱疮	BP180，BP230
瘢痕性类天疱疮	BP180，BP230，层粘连蛋白332