Clinical Immunology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Institute of Protein Biochemistry, National Research Council, Naples, Italy.
Cytokine. 2018 Feb;102:145-148. doi: 10.1016/j.cyto.2017.08.001. Epub 2017 Aug 18.
BACKGROUND/AIM: The IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect almost any organ, often associated with eosinophilia and increased levels of IgE and IgG4. Overexpression in tissues of Th2-related cytokines but also of IFN-γ has been reported. Given the major role of Il-1 family cytokines in inducing and regulating inflammation, and the paucity of data so far available in IgG-RD, we performed a comprehensive analysis of IL-18, related IL-1 family cytokines and soluble receptors in these patients.
Fifteen patients fulfilling the criteria for the diagnosis of IgG4-RD and 80 blood donors as control were recruited. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein -IL-18BP-) were measured in sera by multiarray ELISA assay. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP.
Half of the patients had a multiorgan disease, mainly affecting retroperitoneum, lymph nodes and pancreas. sIL-1R1 (p=0.0001), sIL-1R2 (p=0.0024), ST2/sIL-1R4 (p=0.002) were significantly increased in IgG4-RD sera compared with healthy controls; sIL-R3 was significantly lower in patients vs controls (p=0,0006).
The increased levels of the soluble forms of the two IL-1 receptors IL-1R1 and IL-1R2 suggest the need to dampen IL-1-mediated inflammation at the tissue level. Elevated circulating ST2/sIL-1R4 levels may represent the marker of an ongoing protective mechanism, but their contribution to organ damage cannot be excluded. On the whole, the data suggest a tight control of IL-1 family cytokines signalling in IgG4-RD.
背景/目的：IgG4 相关疾病（IgG4-RD）是一种纤维炎症性疾病，几乎可影响任何器官，常伴有嗜酸性粒细胞增多和 IgE 及 IgG4 水平升高。组织中 Th2 相关细胞因子，甚至 IFN-γ的过表达也有报道。鉴于白细胞介素-1 家族细胞因子在诱导和调节炎症中起重要作用，而 IgG-RD 目前的数据很少，我们对这些患者的 IL-18、相关白细胞介素-1 家族细胞因子和可溶性受体进行了全面分析。
招募了 15 名符合 IgG4-RD 诊断标准的患者和 80 名献血者作为对照。采用多阵列 ELISA 法检测血清中白细胞介素-1 家族（IL-1α、IL-1β、IL-33、IL-18）、可溶性受体（sIL-1R1、sIL-1R2、sIL-1R3、ST2/sIL-1R4）和拮抗剂（IL-1Ra、IL-18 结合蛋白-IL-18BP-）。用 IL-18BP 抑制后计算未被抑制的游离 IL-18。
一半的患者有多器官疾病，主要累及腹膜后、淋巴结和胰腺。与健康对照组相比，IgG4-RD 患者的 sIL-1R1（p=0.0001）、sIL-1R2（p=0.0024）、ST2/sIL-1R4（p=0.002）明显升高；sIL-R3 在患者中明显低于对照组（p=0.0006）。
两种白细胞介素-1 受体 IL-1R1 和 IL-1R2 的可溶性形式水平升高提示需要在组织水平上抑制 IL-1 介导的炎症。循环中 ST2/sIL-1R4 水平升高可能代表一种持续的保护机制，但不能排除其对器官损伤的作用。总的来说，这些数据提示 IgG4-RD 中白细胞介素-1 家族细胞因子信号转导受到严密控制。
