自身免疫性大疱性皮肤病的实验室诊断进展
收稿日期: 2022-02-01
网络出版日期: 2023-11-17
基金资助
国家自然科学基金面上项目(82173407);国家自然科学基金面上项目(82273514)
Advances in laboratory diagnosis of autoimmune bullous dermatoses
Received date: 2022-02-01
Online published: 2023-11-17
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%;EUROTideTM 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
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 . DOI: 10.16150/j.1671-2870.2023.03.16
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. EUROTideTM 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.
[1] | SCHMIDT E, KASPERKIEWICZ M, JOLY P. Pemphigus[J]. The Lancet, 2019, 394(10201):882-894. |
[2] | SCHMIDT E, ZILLIKENS D. Pemphigoid diseases[J]. The Lancet, 2013, 381(9863):320-332. |
[3] | ALPSOY E, AKMAN-KARAKAS A, UZUN S. Geographic variations in epidemiology of two autoimmune bullous diseases: pemphigus and bullous pemphigoid[J]. Arch Dermatol Res, 2015, 307(4):291-298. |
[4] | PORRO A M, SEQUE C A, FERREIRA M C C, et al. Pemphigus vulgaris[J]. An Bras Dermatol, 2019, 94(3):264-278. |
[5] | EGAMI S, YAMAGAMI J, AMAGAI M. Autoimmune bullous skin diseases, pemphigus and pemphigoid[J]. J Allergy Clin Immunol, 2020, 145(4):1031-1047. |
[6] | MIYAMOTO D, SANTI C G, AOKI V, et al. Bullous pemphigoid[J]. An Bras Dermatol, 2019, 94(2):133-146. |
[7] | KRIDIN K, LUDWIG R J. The Growing Incidence of Bullous Pemphigoid: Overview and Potential Explanations[J]. Front Med (Lausanne), 2018, 5:220. |
[8] | DANIEL B S, MURRELL D F. Review of autoimmune blistering diseases: the Pemphigoid diseases[J]. J Eur Acad Dermatol Venereol, 2019, 33(9):1685-1694. |
[9] | SASCHENBRECKER S, KARL I, KOMOROWSKI L, et al. Serological Diagnosis of Autoimmune Bullous Skin Diseases[J]. Front Immunol, 2019, 10:1974. |
[10] | 刘红芳, 薛汝增, 潘慧清, 等. 80例大疱性皮肤病组织病理及直接免疫荧光结果分析[J]. 皮肤性病诊疗学杂志, 2010, 17(3):179-181. |
[10] | LIU H F, XUE R Z, PAN H Q, et al. Analysis of pathology and direct immunofluorescence test on 80 cases of bullous dermatosis[J]. J Diagn Ther on Derm Venereol, 2010, 17(3):179-181. |
[11] | KNEISEL A, HERTL M. Autoimmune bullous skin diseases. Part 1: Clinical manifestations[J]. J Dtsch Dermatol Ges, 2011, 9(10):844-856. |
[12] | 马俊兵, 杨丽颖. 80例大疱性皮肤病组织病理及直接免疫荧光结果分析[J]. 中国农村卫生, 2017(2):71-72. |
[12] | MA J B, YANG L Y. Analysis of pathology and direct immunofluorescence test on 80 cases of bullous dermatosis[J]. Chin Rural Health, 2017(2):71-72. |
[13] | SáRDY M, KOSTAKI D, VARGA R, et al. Comparative study of direct and indirect immunofluorescence and of bullous pemphigoid 180 and 230 enzyme-linked immunosorbent assays for diagnosis of bullous pemphigoid[J]. J Am Acad Dermatol, 2013, 69(5):748-753. |
[14] | GIURDANELLA F, DIERCKS G F, JONKMAN M F, et al. Laboratory diagnosis of pemphigus: direct immunofluorescence remains the gold standard[J]. Br J Dermatol, 2016, 175(1):185-186. |
[15] | 李卫平, 潘萌, 薛峰, 等. 免疫印迹法与免疫荧光法检测寻常型天疱疮自身抗体的比较[J]. 上海免疫学杂志, 2003, 23(1):43-44. |
[15] | LI W P, PAN M, XUE F, et al. Comparison of Immunoblot and Immunofluorescence in Detecting Pemphigus Vulgaris Antibodies[J]. Shanghai J Immunol, 2003, 23(1):43-44. |
[16] | KRIDIN K, BERGMAN R. The usefulness of indirect immunofluorescence in pemphigus and the natural history of patients with initial false-positive results: a retrospective cohort study[J]. Front Med (Lausanne), 2018, 5:266. |
[17] | DI LERNIA V, CASANOVA D M, GOLDUST M, et al. Pemphigus Vulgaris and Bullous Pemphigoid: Update on Diagnosis and Treatment[J]. Dermatol Pract Concept, 2020, 10(3):e2020050. |
[18] | 许人超, 郑捷, 潘萌, 等. 酶联免疫吸附法和免疫印迹技术检测天疱疮抗体的比较[J]. 中国皮肤性病学杂志, 2012, 26(5):452-454. |
[18] | XU R C, ZHENG J, PAN M, et al. Comparison of enzyme-linked immunosorbent assay test with immunoblot assay in the diagnosis of pemphigus[J]. Chin J Derm Venereol, 2012, 26(5):452-454. |
[19] | XUAN R R, YANG A, MURRELL D F. New biochip immunofluorescence test for the serological diagnosis of pemphigus vulgaris and foliaceus: A review of the literature[J]. Int J Womens Dermatol, 2018, 4(2):102-108. |
[20] | WITTE M, ZILLIKENS D, SCHMIDT E. Diagnosis of Autoimmune Blistering Diseases[J]. Front Med (Lausanne), 2018, 5:296. |
[21] | MEIJER J M, DIERCKS G F H, DE LANG E W G, et al. Assessment of Diagnostic Strategy for Early Recognition of Bullous and Nonbullous Variants of Pemphigoid[J]. JAMA Dermatol, 2019, 155(2):158-165. |
[22] | SCHMIDT E, D?HNRICH C, ROSEMANN A, et al. Novel ELISA systems for antibodies to desmoglein 1 and 3: correlation of disease activity with serum autoantibody levels in individual pemphigus patients[J]. Exp Dermatol, 2010, 19(5):458-463. |
[23] | TAMPOIA M, ZUCANO A, VILLALTA D, et al. Anti-skin specific autoantibodies detected by a new immunofluorescence multiplex biochip method in patients with autoimmune bullous diseases[J]. Dermatology, 2012, 225(1):37-44. |
[24] | SADIK C D, PAS H H, BOHLMANN M K, et al. Value of biochip technology in the serological diagnosis of pemphigoid gestationis[J]. Acta Derm Venereol, 2017, 97(1):128-130. |
[25] | VAN BEEK N, KRüGER S, FUHRMANN T, et al. Multicenter prospective study on multivariant diagnostics of autoimmune bullous dermatoses using the BIOCHIP technology[J]. J Am Acad Dermatol, 2020, 83(5):1315-1322. |
[26] | LEMCKE S, SOKOLOWSKI S, RIECKHOFF N, et al. Automated direct immunofluorescence analyses of skin biopsies[J]. J Cutan Pathol, 2016, 43(3):227-235. |
[27] | HORVáTH O N, VARGA R, KANEDA M, et al. Diagnostic performance of the “MESACUP anti-Skin profile TEST”[J]. Eur J Dermatol, 2016, 26(1):56-63. |
[28] | SCHMIDT T, MAURACHER S, BENDER L. et al. A novel lateral flow immunoassay for the rapid detection of anti-Dsg3 IgG serum autoantibodies in pemphigus vulgaris[J]. Exp Dermatol, 2018, 27(3):233-237. |
[29] | FUJIO Y, KOJIMA K, HASHIGUCHI M, et al. Validation of chemiluminescent enzyme immunoassay in detection of autoantibodies in pemphigus and pemphigoid[J]. J Dermatol Sci, 2017, 85(3):208-215. |
[30] | TANAKA R, TAKEMURA M, SATO M, et al. Comparison of chemiluminescence enzyme immunoassay (CLEIA) with ELISA for the determination of anti-cyclic citrullinated peptide antibodies[J]. Clin Chim Acta, 2010, 411(1-2):22-25. |
[31] | WOZNIAK K, JAKUBOWSKA B, KALINSKA-BIENIAS A, et al. Diagnosis of autoimmune subepidermal bullous diseases with mucous membrane involvement based on laser-scanning confocal microscopy[J]. Eur J Dermatol, 2020, 30(5):516-523. |
[32] | WOZNIAK K, KAZAMA T, KOWALEWSKI C. A practical technique for differentiation of subepidermal bullous diseases: localization of in vivo-bound IgG by laser scanning confocal microscopy[J]. Arch Dermatol, 2003, 139(8):1007-1011. |
[33] | PROST-SQUARCIONI C, CAUX F, SCHMIDT E, et al. International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita[J]. Br J Dermatol, 2018, 179(1):30-41. |
[34] | KITAYAMA S, MAKINO T, HAYASHI M, et al. Usefulness of immunofluorescence overlay antigen mapping in the identification of autoantigen in anti-p200 pemphigoid[J]. J Dermatol, 2023, 50(9):1194-1198. |
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