Superantigen-Induced Glucocorticoid Insensitivity in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps

Superantigen-Induced Glucocorticoid Insensitivity in the Recurrence of Chronic Rhinosinusitis with Nasal Polyps
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超抗原诱导的糖皮质激素不敏感导致慢性鼻窦炎伴鼻息肉复发

DOI:
10.1177/0194599811413859
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发表时间:
2011-11-01
影响因子:
3.4
通讯作者:
Wang, Haibo
Wang, Haibo
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Mingming;Shi, Peng;Wang, Haibo

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目标。探讨超抗原诱导慢性鼻-鼻窦炎(CRS)患者糖皮质激素不敏感的可能机制。前瞻性队列研究。第三医学中心。研究对象和方法。鼻息肉来自CRS合并鼻息肉(CRSwNP,20例无复发,18例复发,随访1.5~2.0年)和16例CRS无鼻息肉(CRSsNP)患者的鼻黏膜。用酶联免疫吸附试验检测葡萄球菌外毒素(SE),包括SEA、SEB、SEC、SED和中毒性休克综合征毒素-1(TSST-1),用免疫组织化学方法检测糖皮质激素受体(GR)α和β,并分析GRβ/GRα比值。在CRSwNP中,18例复发性NP患者中13例(72.22%),20例未复发NP患者中11例(55.00%),16例SES阳性患者中1例(6.25%)。对照组没有阳性结果。3组CRS患者GRβ表达与对照组比较差异均有统计学意义(均P<0.05),除CRSwNP组与复发性NP组比较外,GRβ/GRα比值也有相似的升高趋势(P=0.053)。此外,在酶联免疫吸附试验(ELISA)阳性的样本中,GRβ的表达与阴性的样本相比有明显的增加趋势。对于GRα,只有在毒素阳性的复发性NP中GRα的表达显著高于对照组(P=0.048),但GRβ的相对诱导率要高得多,从而导致GRβ/GRα的比率更高。细菌超抗原可能通过诱导GRβ而导致糖皮质激素不敏感,而GRβ似乎是CRSwNP激素不敏感的标志。
Objective. To investigate a potential mechanism by which superantigens could induce glucocorticoid insensitivity in chronic rhinosinusitis (CRS) patients.Study Design. Prospective cohort study.Setting. Tertiary medical center.Subjects and Methods. Sinonasal polyps were obtained from CRS patients with nasal polyps (CRSwNP; 20 without recurrence, 18 with recurrent NP followed for 1.5-2.0 years) and nasal mucosa from 16 CRS patients without nasal polyps (CRSsNP). Specimens were tested by enzyme-linked immunosorbent assay for staphylococcal exotoxins (SEs) including SEA, SEB, SEC, SED, and toxic shock syndrome toxin type-1 (TSST-1) and assessed by immunohistochemistry for glucocorticoid receptor (GR) alpha and beta, and the GR beta/GR alpha ratio was analyzed.Results. In CRSwNP, 13 of 18 (72.22%) subjects with subsequently recurrent NP, 11 of 20 (55.00%) subjects without NP recurrence, and 1 of 16 (6.25%) CRSsNP subjects with positive reactions for SEs were obtained. There were no positive results in controls. The expressions of GR beta in 3 CRS groups and controls were significantly different (all P < .05), and a similar increasing tendency of the GR beta/GR alpha ratio was found among groups besides the comparison of CRSwNP versus recurrent NP groups (P = .053). Furthermore, there was a clear trend of increased GR beta expression in the enzyme-linked immunosorbent assay (ELISA)-positive samples compared with ELISA-negative samples. Concerning GR alpha, the expression was enhanced significantly just in toxin-positive recurrent NP versus controls (P = .048), but the relative induction of GR beta was much higher, thereby leading to a higher GR beta/GR alpha ratio.Conclusions. Bacterial superantigens may contribute to glucocorticoid insensitivity through induction of GR beta, which appears to be a marker of steroid insensitivity in CRSwNP.