酶联免疫斑点法在重症药疹致敏药物鉴定中的应用

doi:10.3760/cma.j.issn.0412-4030.2019.06.015

中华皮肤科杂志 ›› 2019, Vol. 52 ›› Issue (6): 436-439.doi: 10.3760/cma.j.issn.0412-4030.2019.06.015

酶联免疫斑点法在重症药疹致敏药物鉴定中的应用

高雪梅章星琪王芳

中山大学附属第一医院皮肤科，广州 510080

收稿日期:2018-05-09 修回日期:2018-12-18 发布日期:2019-06-03
通讯作者: 王芳 E-mail:ffwang.640@163.com
基金资助:
国家自然科学基金（81703111）；广东省自然科学基金（2016A030313246）

Application of enzyme?linked immunospot assay in the identification of culprit drugs in severe drug eruptions

Gao Xuemei, Zhang Xingqi, Wang Fang

Department of Dermatology, The First Affiliated Hospital, Sun Yat⁃sen University, Guangzhou 510080, China

Received:2018-05-09 Revised:2018-12-18 Published:2019-06-03
Contact: Wang Fang E-mail:ffwang.640@163.com
Supported by:
National Natural Science Foundation of China （81703111）; Natural Science Foundation of Guangdong Province of China （2016A030313246）

摘要/Abstract

摘要： 【摘要】早期发现致敏药物对重症药疹的防治至关重要。目前对重症药疹致敏药物的鉴定尚无准确有效的检测方法，已有的斑贴试验、淋巴细胞转化实验等，因敏感度和特异度较低，难以广泛应用。酶联免疫斑点法通过在体外检测药物特异性T淋巴细胞分泌的细胞因子鉴定致敏药物，在重症药疹患者中具有较高的敏感度及特异度，并可应用于处于疾病早期及合并免疫抑制性疾病的药疹患者。酶联免疫斑点法可能成为鉴定重症药疹致敏药物的有效方法。

关键词: 药疹, 酶联免疫斑点测定, 干扰素γ释放试验, 敏感性与特异性, 致敏药物

Abstract: 【Abstract】 Early identification of culprit drugs is crucial for the treatment and prevention of severe drug eruptions. At present, no accurate and effective methods are available for identifying the culprit drugs in severe drug eruptions. Commonly used tests include patch test, lymphocyte transformation test and so on. However, low sensitivity and specificity limit their clinical application. Enzyme-linked immunospot assay, an in vitro technique, can identify culprit drugs in cutaneous adverse drug reactions by detecting cytokines secreted by drug-specific T lymphocytes. It has high sensitivity and specificity in patients with severe drug eruptions, and can be carried out during the acute stage of disease or among immunocompromised patients. Therefore, enzyme-linked immunospot assay may be an effective method for identifying culprit drugs in severe drug eruptions.

Key words: Drug eruptions, Enzyme-linked immunospot assay, Interferon-gamma release tests, Sensitivity and specificity, Culprit drugs

高雪梅章星琪王芳. 酶联免疫斑点法在重症药疹致敏药物鉴定中的应用[J]. 中华皮肤科杂志, 2019,52(6):436-439. doi:10.3760/cma.j.issn.0412-4030.2019.06.015

Gao Xuemei, Zhang Xingqi, Wang Fang. Application of enzyme?linked immunospot assay in the identification of culprit drugs in severe drug eruptions[J]. Chinese Journal of Dermatology, 2019, 52(6): 436-439.doi:10.3760/cma.j.issn.0412-4030.2019.06.015

参考文献 27

［1］	Duong TA, Valeyrie⁃Allanore L, Wolkenstein P, et al. Severe cutaneous adverse reactions to drugs［J］. Lancet, 2017,390（10106）:1996⁃2011. doi: 10.1016/S0140⁃6736（16）30378⁃6.
［2］	Hoetzenecker W, Nägeli M, Mehra ET, et al. Adverse cutaneous drug eruptions: current understanding［J］. Semin Immunopathol, 2016,38（1）:75⁃86. doi: 10.1007/s00281⁃015⁃0540⁃2.
［3］	Chung WH, Wang CW, Dao RL. Severe cutaneous adverse drug reactions［J］. J Dermatol, 2016,43（7）:758⁃766. doi: 10.1111/jde. 2016.43.issue⁃7.
［4］	Peter JG, Lehloenya R, Dlamini S, et al. Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice［J］. J Allergy Clin Immunol Pract, 2017,5（3）:547⁃563. doi: 10.1016/j.jaip.2017.01. 025.
［5］	Beeler A, Engler O, Gerber BO, et al. Long⁃lasting reactivity and high frequency of drug⁃specific T cells after severe systemic drug hypersensitivity reactions［J］. J Allergy Clin Immunol, 2006,117（2）:455⁃462. doi: 10.1016/j.jaci.2005.10.030.
［6］	Wang F, Cai R, He D, et al. Serum IFN⁃γ⁃inducible chemokines CXCL9 and CXCL10 are elevated in non⁃immediate drug hypersensitivity reactions［J］. Asian Pac J Allergy Immunol, 2016,34（3）:236⁃241. doi: 10.12932/AP0679
［7］	Czerkinsky CC, Nilsson LA, Nygren H, et al. A solid⁃phase enzyme⁃linked immunospot （ELISPOT） assay for enumeration of specific antibody⁃secreting cells［J］. J Immunol Methods, 1983,65（1⁃2）:109⁃121. doi: 10.1016/0022⁃1759（83）90308⁃3.
［8］	Su SC, Chung WH. Cytotoxic proteins and therapeutic targets in severe cutaneous adverse reactions［J］. Toxins （Basel）, 2014,6（1）:194⁃210. doi: 10.3390/toxins6010194.
［9］	Polak ME, Belgi G, McGuire C, et al. In vitro diagnostic assays are effective during the acute phase of delayed⁃type drug hypersensitivity reactions［J］. Br J Dermatol, 2013,168（3）:539⁃549. doi: 10.1111/bjd.2013.168.issue⁃3.
［10］	Haw WY, Polak ME, McGuire C, et al. In vitro rapid diagnostic tests for severe drug hypersensitivity reactions in children［J］. Ann Allergy Asthma Immunol, 2016,117（1）:61⁃66. doi: 10.1016/j.anai.2016.04.017.
［11］	Klaewsongkram J, Thantiworasit P, Suthumchai N, et al. In vitro test to confirm diagnosis of allopurinol⁃induced severe cutaneous adverse reactions［J］. Br J Dermatol, 2016,175（5）:994⁃1002. doi: 10.1111/bjd.2016.175.issue⁃5.
［12］	Porebski G, Pecaric⁃Petkovic T, Groux⁃Keller M, et al. In vitro drug causality assessment in Stevens⁃Johnson syndrome ⁃ alterna⁃tives for lymphocyte transformation test［J］. Clin Exp Allergy, 2013,43（9）:1027⁃1037. doi: 10.1111/cea.2013.43.issue⁃9.
［13］	Chung WH, Hung SI, Yang JY, et al. Granulysin is a key mediator for disseminated keratinocyte death in Stevens⁃Johnson syndrome and toxic epidermal necrolysis［J］. Nat Med, 2008,14（12）:1343⁃1350. doi: 10.1038/nm.1884.
［14］	Abe R, Yoshioka N, Murata J, et al. Granulysin as a marker for early diagnosis of the Stevens⁃Johnson syndrome［J］. Ann Intern Med, 2009,151（7）:514⁃515. doi: 10.7326/0003⁃4819⁃151⁃7⁃200910060⁃00016.
［15］	Wang F, Ye Y, Luo ZY, et al. Diverse of TNF⁃α and CCL27 in serum and blister of Stevens⁃Johnson syndrome/toxic epidermal necrolysis［J］. Clin Transl Allergy, 2018,8:12. doi: 10. 1186/s13601⁃018⁃0199⁃6.
［16］	Ogawa K, Morito H, Hasegawa A, et al. Elevated serum thymus and activation⁃regulated chemokine （TARCCCL17） relates to reactivation of human herpesvirus 6 in drug reaction with eosinophilia and systemic symptoms （DRESS）drug⁃induced hypersensitivity syndrome （DIHS）［J］. Br J Dermatol, 2014,171（2）:425⁃427. doi: 10.1111/bjd.12948.
［17］	White KD, Chung WH, Hung SI, et al. Evolving models of the immunopathogenesis of T cell⁃mediated drug allergy: the role of host, pathogens, and drug response［J］. J Allergy Clin Immunol, 2015,136（2）:219⁃234. doi: 10.1016/j.jaci.2015.05.050.
［18］	Esser S, Jablonka R, Heinemann FM, et al. Detection of abacavir hypersensitivity by ELISpot method［J］. Inflamm Allergy Drug Targets, 2012,11（3）:227⁃234. doi: 10.2174/187152812800392751.
［19］	Gibson A, Ogese M, Sullivan A, et al. Negative regulation by PD⁃L1 during drug⁃specific priming of IL⁃22⁃secreting T cells and the influence of PD⁃1 on effector T cell function［J］. J Immunol,2014,192（6）:2611⁃2621. doi: 10.4049/jimmunol.1302720.
［20］	Kato K, Kawase A, Azukizawa H, et al. Novel interferon⁃γ enzyme⁃linked immunoSpot assay using activated cells for identifying hypersensitivity⁃inducing drug culprits［J］. J Dermatol Sci, 2017,86（3）:222⁃229. doi: 10.1016/j.jdermsci.2017.03.007.
［21］	Adler NR, Aung AK, Ergen EN, et al. Recent advances in the understanding of severe cutaneous adverse reactions［J］. Br J Dermatol, 2017,177（5）:1234⁃1247. doi: 10.1111/bjd.15423.
［22］	Barbaud A, Collet E, Milpied B, et al. A multicentre study to determine the value and safety of drug patch tests for the three main classes of severe cutaneous adverse drug reactions［J］. Br J Dermatol, 2013,168（3）:555⁃562. doi: 10.1111/bjd.2013.168.issue⁃3.
［23］	Wolkenstein P, Chosidow O, Flechet ML, et al. Patch testing in severe cutaneous adverse drug reactions,including Stevens⁃Johnson syndrome and toxic epidermal necrolysis［J］. Contact Dermatitis, 1996,35（4）:234⁃236. doi: 10.1111/j.1600⁃0536.1996. tb02364.x.
［24］	Agache I, Bilo M, Braunstahl GJ, et al. In vivo diagnosis of allergic diseases⁃⁃allergen provocation tests［J］. Allergy, 2015,70（4）:355⁃365. doi: 10.1111/all.2015.70.issue⁃4.
［25］	Pichler WJ, Tilch J. The lymphocyte transformation test in the diagnosis of drug hypersensitivity［J］. Allergy, 2004,59（8）:809⁃820. doi: 10.1111/all.2004.59.issue⁃8.
［26］	Cabanas R, Calderon O, Ramirez E, et al. Sensitivity and specificity of the lymphocyte transformation test in drug reaction with eosinophilia and systemic symptoms causality assessment［J］. Clin Exp Allergy, 2018,48（3）:325⁃333. doi: 10.1111/cea. 2018.48.issue⁃3.
［27］	Trubiano JA, Strautins K, Redwood AJ, et al. The combined utility of ex vivo IFN⁃gamma release enzyme⁃linked immunoSpot assay and in vivo skin testing in patients with antibiotic⁃associated severe cutaneous adverse reactions［J］. J Allergy Clin Immunol Pract, 2018,6（4）:1287⁃1296.e1. doi: 10. 1016/j.jaip. 2017.09.004.

[1]	徐文凌昕施辛万聪翀戴彩红杨志刚陈玲玲. 特应性皮炎张氏诊断标准在苏南地区青少年和成人的适用性评估[J]. 中华皮肤科杂志, 2022, 55(12): 1084-1088.
[2]	龙海蒋丽邱月棨姚南刘力聪谢昱明熊峰谭思齐匡琪琪尤睿璇柴可罗鑫龙浩君忻悦郭子瑜王佳琪谭怡忻张庆张桂英李亚萍苏玉文肖嵘陆前进, . 皮肤科病房危重症1 057例临床分析[J]. 中华皮肤科杂志, 2021, 54(9): 790-797.
[3]	中华医学会皮肤性病学分会药物不良反应研究中心. Stevens-Johnson综合征/中毒性表皮坏死松解症诊疗专家共识[J]. 中华皮肤科杂志, 2021, 54(5): 376-381.
[4]	徐蓓蕾姚煦. 过敏原特异性T细胞检测方法的研究进展[J]. 中华皮肤科杂志, 2021, 54(4): 364-367.
[5]	康莉刘艳郑云燕鞠梅张亚美毕志刚芦桂青. 马血清破伤风抗毒素与马破伤风免疫球蛋白F（ab′）₂引起的皮肤迟发型变态反应临床分析[J]. 中华皮肤科杂志, 2021, 54(3): 226-228.
[6]	邓思思王欢余南岚黎松宋志强. 药物超敏反应综合征45例临床特点分析[J]. 中华皮肤科杂志, 2021, 54(2): 127-130.
[7]	姚翠玲王紫涵胡景景高昱丁长玲. 63例重症药疹住院患者发热及肝损伤特征分析[J]. 中华皮肤科杂志, 2021, 54(11): 984-989.
[8]	肖扬张晓光. 拉莫三嗪所致药疹的研究进展[J]. 中华皮肤科杂志, 2021, 54(10): 927-930.
[9]	渠莉田方意红苏惠春程波. 中毒性表皮坏死松解症合并噬血细胞综合征一例[J]. 中华皮肤科杂志, 2020, 53(9): 732-734.
[10]	霍玉萍陈柏嘉钟文宏. 林可霉素致急性泛发性发疹性脓疱病一例[J]. 中华皮肤科杂志, 2018, 51(7): 531-533.
[11]	闫志华李施清施辛苏玉华经晶李纪兵张婷徐丰谈星陈玲玲. 肿瘤坏死因子α拮抗剂治疗别嘌醇所致药疹后重新发热：药疹未控制？[J]. 中华皮肤科杂志, 2017, 50(12): 920-921.
[12]	陈官芝张洋路晓琳时培荣徐光勇孙梦绮李志涛刘信桥周惠赵娟. HIV阳性药疹患者CD4+、CD8+T细胞水平以及临床特征分析[J]. 中华皮肤科杂志, 2015, 48(12): 853-856.
[13]	刘爱英訾绍霞杨万石史振伟. 甲泼尼松联合血浆置换治疗大疱性表皮松解坏死型药疹一例[J]. 中华皮肤科杂志, 2012, 45(10): 757-757.
[14]	鲁严苏忠兰张涛骆丹. 卡马西平致重症药疹合并抗利尿激素分泌不当综合征一例[J]. 中华皮肤科杂志, 2011, 44(4): 292-293.
[15]	赵桂芝韩慧霞宋秋荷钟白玉陆洪光王鲁. 白念珠菌芽管特异性抗原快速检测方法的建立和初步评价[J]. 中华皮肤科杂志, 2011, 44(12): 861-864.

酶联免疫斑点法在重症药疹致敏药物鉴定中的应用

Application of enzyme?linked immunospot assay in the identification of culprit drugs in severe drug eruptions

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 27

相关文章 15

Metrics

本文评价

推荐阅读 10