Serum Soluble OX40 as a Diagnostic and Prognostic Biomarker for Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms
Serum Soluble OX40 as a Diagnostic and Prognostic Biomarker for Drug-Induced Hypersensitivity Syndrome/Drug Reaction with Eosinophilia and Systemic Symptoms
复制标题
DOI：
10.1016/j.jaip.2021.10.042
复制
发表时间：
2022-02-07
影响因子：
9.4
通讯作者：
Asada, Hideo
中科院分区：
文献类型：
--
作者：
Mitsui, Yasuhiro;Shinkuma, Satoru;Asada, Hideo
背景技术背景：药物诱导的超敏反应综合征/药物反应伴嗜酸性粒细胞增多和全身症状（DIHS/ DRESS）是一种严重的药物不良反应，通常与人类疱疹病毒6型（HHV-6）的再活化相关。目前还没有足够的生物标志物用于DIHS/DRESS的早期诊断和检测。值得注意的是，OX 40（CD 134）在过敏性炎症中具有重要作用，并作为HHV-6进入的细胞受体发挥作用。我们以前报道过CD 4 + T细胞中的OX 40的膜结合形式在DIHS/DRESS中上调。目的：探讨血清可溶性OX 40（sOX 40）在DIHS/DRESS中的临床意义。方法：采用酶联免疫吸附试验检测了DIHS/DRESS患者（n = 39）、斑丘疹性皮肤病/多形性红斑患者（n = 17）、Stevens-Johnson综合征/中毒性表皮坏死松解症患者（n = 13）、自身免疫性大疱病患者（n = 5）和健康志愿者（n = 5）的血清sOX 40水平。使用实时PCR定量外周血单个核细胞中HHV-6、HHV-7和巨细胞病毒的拷贝数。结果：DIHS/DRESS患者急性期血清sOX 40水平升高，与CD 4 + T细胞OX 40高表达平行。血清sOX 40水平与疾病严重程度、血清胸腺和活化调节趋化因子、IL-5和IL-10水平显著正相关。人类疱疹病毒6型阳性患者sOX 40水平高于HHV-6阴性患者，血清sOX 40水平与HHV-6 DNA载量相关。结论：血清sOX 40水平可作为反映疾病严重程度的DIHS/DRESS的诊断指标。血清sOX 40水平升高也可预测DIHS/DRESS患者中HHV-6的再活化。(c)2021年美国过敏、哮喘和免疫学学会（J Allergy Clin Immunol Pract 2022;10：558-65）
BACKGROUND: Drug-induced hypersensitivity syndrome/ drug reaction with eosinophilia and systemic symptoms (DIHS/ DRESS) is a severe adverse drug reaction commonly associated with the reactivation of human herpesvirus 6 (HHV-6). There are currently no adequate biomarkers for the early diagnosis and detection of DIHS/DRESS. Notably, OX40 (CD134) has an important role in allergic inflammation and functions as a cellular receptor for HHV-6 entry. We previously reported that the membrane-bound form of OX40 in CD4+ T cells was upregulated in DIHS/DRESS. OBJECTIVE: We sought to investigate the clinical significance of serum soluble OX40 (sOX40) in DIHS/DRESS. METHODS: Serum sOX40 levels in patients with DIHS/DRESS (n = 39), maculopapular exanthema/erythema multiforme (n = 17), Stevens-Johnson syndrome/toxic epidermal necrolysis (n = 13), or autoimmune bullous diseases (n = 5), and levels in healthy volunteers (n = 5) were examined by enzyme-linked immunosorbent assay. Copy numbers of HHV-6, HHV-7, and cytomegalovirus in peripheral blood mononuclear cells were quantified using real-time PCR. RESULTS: Serum sOX40 levels in patients with DIHS/DRESS in the acute stage were elevated in parallel with high OX40 expression on CD4+ T cells. Serum sOX40 levels were significantly positively correlated with disease severity and serum levels of thymus and activation-regulated chemokine, IL-5, and IL-10. Human herpesvirus 6-positive patients had higher sOX40 levels than did HHV-6-negative patients, and serum sOX40 levels were correlated with HHV-6 DNA loads. CONCLUSIONS: Serum sOX40 levels can be a useful diagnostic marker for DIHS/DRESS that reflect disease severity. Elevated serum sOX40 levels also predict HHV-6 reactivation in patients with DIHS/DRESS. (c) 2021 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2022;10:558-65)