Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): A Multiorgan Antiviral T Cell Response
复制标题
DOI：
10.1126/scitranslmed.3001116
复制
发表时间：
2010-08-25
影响因子：
17.1
通讯作者：
Musette, Philippe
中科院分区：
文献类型：
--
作者：
Picard, Damien;Janela, Baptiste;Musette, Philippe
嗜酸性粒细胞增多和全身症状的药物反应（DRESS）是一种严重的药物引起的反应，涉及皮肤和内脏。在一些DRESS患者中发现了疱疹家族病毒再激活的证据。为了了解DRESS的免疫学成分及其与病毒再激活的关系，我们前瞻性地评估了40例卡马西平、别嘌呤醇或磺胺甲恶唑治疗后出现DRESS的患者。评估患者外周血T淋巴细胞的表型、细胞因子分泌、CD4（+）和CD8（+）储备以及病毒再激活。我们在76%的患者中发现了eb病毒（EBV）、人类疱疹病毒6 （HHV-6）或HHV-7再激活。在所有患者中，循环CD8(+) T淋巴细胞被激活，表现出皮肤归巢标记物增加，分泌大量肿瘤坏死因子-a和干扰素-g。这些细胞因子的产生在最严重的内脏受累的患者中特别高。此外，在患者的血液、皮肤、肝脏和肺部检测到具有相同T细胞受体库的CD8(+) T淋巴细胞的扩增群体。这些扩增的血液CD8(+) T淋巴细胞中有近一半特异性识别EBV表位之一。最后，我们发现罪魁祸首药物触发EBV在患者转化EBV的B淋巴细胞中产生。因此，DRESS的皮肤和内脏症状是由活化的CD8(+) T淋巴细胞介导的，这些T淋巴细胞主要针对疱疹病毒，如EBV。
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, drug-induced reaction that involves both the skin and the viscera. Evidence for reactivation of herpes family viruses has been seen in some DRESS patients. To understand the immunological components of DRESS and their relationship to viral reactivation, we prospectively assessed 40 patients exhibiting DRESS in response to carbamazepine, allopurinol, or sulfamethoxazole. Peripheral blood T lymphocytes from the patients were evaluated for phenotype, cytokine secretion, and repertoire of CD4(+) and CD8(+) and for viral reactivation. We found Epstein-Barr virus (EBV), human herpes virus 6 (HHV-6), or HHV-7 reactivation in 76% of the patients. In all patients, circulating CD8(+) T lymphocytes were activated, exhibited increased cutaneous homing markers, and secreted large amounts of tumor necrosis factor-a and interferon-g. The production of these cytokines was particularly high in patients with the most severe visceral involvement. In addition, expanded populations of CD8(+) T lymphocytes sharing the same T cell receptor repertoire were detected in the blood, skin, liver, and lungs of patients. Nearly half of these expanded blood CD8(+) T lymphocytes specifically recognized one of several EBV epitopes. Finally, we found that the culprit drugs triggered the production of EBV in patients' EBV-transformed B lymphocytes. Thus, cutaneous and visceral symptoms of DRESS are mediated by activated CD8(+) T lymphocytes, which are largely directed against herpes viruses such as EBV.