Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome.
Integrating longitudinal serum IL-17 and IL-23 follow-up, along with autoantibodies variation, contributes to predict bullous pemphigoid outcome.
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DOI：
10.1038/srep18001
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发表时间：
2015-12-14
影响因子：
4.6
通讯作者：
Bernard P
中科院分区：
文献类型：
--
作者：
Plée J;Le Jan S;Giustiniani J;Barbe C;Joly P;Bedane C;Vabres P;Truchetet F;Aubin F;Antonicelli F;Bernard P
大疱性类天疱疮（BP）是一种炎症性自身免疫性大疱性疾病，在水疱形成过程中涉及细胞因子和蛋白酶。最近，IL-17和IL-23在BP患者诊断时的皮损和血清中被证实，但它们与疾病结局的关系尚未被研究。然后，我们分析了治疗后第一个月随访期间的IL-17和IL-23血清水平。与年龄和性别相匹配的对照组相比，BP患者血清中IL-23水平在基线时较高（P < 0.01），而IL-17水平则不高。然而，一些BP患者表达高IL-17血清水平，独立于疾病的严重程度。在这些患者中，持续缓解的患者在治疗后降低了IL-17浓度（P < 0.001），而复发患者的IL-17水平仍然升高。治疗1个月后复发的BP患者血清IL-23水平升高（P < 0.01），MMP-9水平未得到控制。因此，我们发现IL-17和IL-23都增加了体外白细胞分泌MMP-9。然后，我们发现升高的IL-17/IL-23血清浓度有助于区分后来复发的BP患者。这种不受控制的炎症反应提出了一个问题，即这些分子是否可以成为对类固醇治疗耐药的BP患者的生物靶点。
Bullous pemphigoid (BP) is an inflammatory autoimmune bullous disease involving cytokines and proteases in the process of blister formation. Recently, IL-17 and IL-23 were evidenced in lesional skin and serum of BP patients at time of diagnosis, but their involvement in disease outcome has still not been investigated yet. We then analysed IL-17 and IL-23 serum levels during the first months of follow-up upon treatment. Compared with age- and sex- matched controls, high levels of IL-23 were observed at baseline in BP patients serum (P < 0.01), while IL-17 levels was not. However, some BP patients expressed high IL-17 serum level, independently of disease severity. In these patients, those with ongoing remission reduced IL-17 concentration upon treatment (P < 0.001), whereas IL-17 level remained elevated in patients who relapsed. Meanwhile, IL-23 serum levels increased during the first month of treatment in BP patients who later relapsed (P < 0.01) and MMP-9 serum level was not controlled. Accordingly, we found that both IL-17 and IL-23 increased MMP-9 secretion from leukocytes in-vitro. Then, we showed that elevated IL-17/IL-23 serum concentrations helped to discriminate BP patients who later relapsed. Such uncontrolled inflammatory response raises the question whether these molecules could become biological target for BP patients resistant to steroid treatment.