Lopalco Giuseppe, Lucherini Orso Maria, Lopalco Antonio, Venerito Vincenzo, Fabiani Claudia, Frediani Bruno, Galeazzi Mauro, Lapadula Giovanni, Cantarini Luca, Iannone Florenzo
Department of Emergency and Organ Transplantation, Rheumatology Unit, University of Bari Aldo Moro , Bari , Italy.
Research Center of Systemic Autoinflammatory Diseases and Behçet's Disease Clinic, Department of Medical Sciences, Surgery and Neurosciences, University of Siena , Siena , Italy.
Front Immunol. 2017 Feb 27;8:200. doi: 10.3389/fimmu.2017.00200. eCollection 2017.
Behçet's disease (BD) is a multi-systemic inflammatory disorder consisting of recurrent oral aphthosis, genital ulcers, and chronic relapsing bilateral uveitis; however, many other organs may be affected. Several pro-inflammatory cytokines, mainly derived from Th1 and Th17 lymphocytes, seem to be involved in different pathogenic pathways leading to development of the clinical manifestations. On this basis, the primary aim of our study was to compare a core set of pro-inflammatory cytokines between patients with BD and healthy control (HC). The secondary goal was to evaluate potential correlations between these putative circulating biomarkers, the status of disease activity, and the specific organ involvement at the time of sample collection. Fifty-four serum samples were collected from 46 BD patients (17 males, 29 females, mean age 45.5 ± 11.3 years), and 19 HC (10 males, 9 females, mean age 43 ± 8.3 years). Twenty-five serum cytokines (APRIL/TNFS13, BAFF/TNFSF13B, sCD30/TNFRSF8, sCD163, Chitinase3-like1, gp130/sIL-6Rb, IFNb, sIL-6Ra, IL-10, IL-11, IL-19, IL-20, IL-26, IL-27 (p28), IL-28A/IFN-lambda2, IL-29/IFN-lambda1, IL-32, IL-34, IL-35, LIGHT/TNFSF-14, Pentraxin-3, sTNF-R1, sTNF-R2, TSLP, and TWEAK/TNFSF-12) were simultaneously quantified using a Bio-Rad cytokine bead arrays. Serum concentration of sTNF-R1 ( < 0.01) and sTNF-R2 ( < 0.01) resulted higher in both active and inactive BD than HC, while Chitinase3-like1 ( < 0.05) and gp130/sIL-6Rb ( < 0.01) serum levels were significantly higher in inactive BD, and IL-26 ( < 0.01) in active BD than HC. No differences were observed between inactive and active BD group. In addition, we observed that gp130/sIL-6Rb, sIL-6Ra, IL-35, and TSLP serum levels were significantly enhanced in patients with mucocutaneous manifestations plus ocular involvement (MO-BD) compared to subgroup with only mucocutaneous involvement (M-BD). Our findings may suggest a signature of IL-6, tumor necrosis factor-α as well as of Th17 response in BD patients due to increased levels of gp130/sIL-6Rb, sTNF-R1, sTNF-R2, IL-26, respectively. This evidence could contribute to improve the knowledge regarding the role of these citokines in the induction of specific BD clinical features.
白塞病（BD）是一种多系统炎症性疾病，由复发性口腔溃疡、生殖器溃疡和慢性复发性双侧葡萄膜炎组成；然而，许多其他器官也可能受到影响。几种主要源自Th1和Th17淋巴细胞的促炎细胞因子似乎参与了导致临床表现发展的不同致病途径。在此基础上，我们研究的主要目的是比较BD患者和健康对照（HC）之间一组核心促炎细胞因子。次要目标是评估这些假定的循环生物标志物、疾病活动状态以及样本采集时特定器官受累情况之间的潜在相关性。从46例BD患者（17例男性，29例女性，平均年龄45.5±11.3岁）和19例HC（10例男性，9例女性，平均年龄43±8.3岁）中采集了54份血清样本。使用Bio-Rad细胞因子珠阵列同时定量25种血清细胞因子（增殖诱导配体/肿瘤坏死因子超家族成员13、B细胞活化因子/肿瘤坏死因子超家族成员13B、可溶性CD30/肿瘤坏死因子受体超家族成员8、可溶性CD163、几丁质酶3样蛋白1、糖蛋白130/可溶性白细胞介素-6受体β、干扰素β、可溶性白细胞介素-6受体α、白细胞介素-10、白细胞介素-11、白细胞介素-19、白细胞介素-20、白细胞介素-26、白细胞介素-27（p28）、白细胞介素-28A/干扰素λ2、白细胞介素-29/干扰素λ1、白细胞介素-32、白细胞介素-34、白细胞介素-35、淋巴毒素相关诱导配体/肿瘤坏死因子超家族成员14、五聚素-3、可溶性肿瘤坏死因子受体1、可溶性肿瘤坏死因子受体2、胸腺基质淋巴细胞生成素和肿瘤坏死因子样弱凋亡诱导因子/肿瘤坏死因子超家族成员12）。在活动期和非活动期BD患者中，可溶性肿瘤坏死因子受体1（<0.01）和可溶性肿瘤坏死因子受体2（<0.01）的血清浓度均高于HC，而非活动期BD患者中几丁质酶3样蛋白1（<0.05）和糖蛋白130/可溶性白细胞介素-6受体β（<0.01）的血清水平显著高于HC，活动期BD患者中白细胞介素-26（<0.01）的血清水平高于HC。非活动期和活动期BD组之间未观察到差异。此外，我们观察到，与仅皮肤黏膜受累的亚组（M-BD）相比，皮肤黏膜表现加眼部受累的患者（MO-BD）中糖蛋白130/可溶性白细胞介素-6受体β、可溶性白细胞介素-6受体α、白细胞介素-35和胸腺基质淋巴细胞生成素的血清水平显著升高。我们的研究结果可能表明，由于糖蛋白130/可溶性白细胞介素-6受体β、可溶性肿瘤坏死因子受体1、可溶性肿瘤坏死因子受体2、白细胞介素-26水平升高，BD患者中存在白细胞介素-6、肿瘤坏死因子-α以及Th17反应的特征。这一证据可能有助于增进对这些细胞因子在诱导BD特定临床特征中作用的认识。
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