University of California, San Francisco, Division of Pulmonary and Critical Care, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
University of California, San Francisco, Division of Pulmonary and Critical Care, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
Respir Med. 2020 Jan;161:105822. doi: 10.1016/j.rmed.2019.105822. Epub 2019 Nov 20.
Sarcoidosis is a granulomatous inflammatory disease with limited blood markers to predict outcomes. The interferon-gamma (IFN-γ)-inducible chemotactic cytokines (chemokines), CXCL9 and CXCL10, are both increased in sarcoidosis patients, yet they possess important molecular differences. Our study determined if serum chemokines correlated with different aspects of disease severity.
We measured CXCL9 and CXCL10 serum levels at initial study visits and longitudinally in sarcoidosis subjects using ELISA. We examined these chemokines' relationships with pulmonary and organ involvement outcomes, their gene expression, peripheral blood immune cell populations, and immunosuppression use.
Higher CXCL10 levels negatively correlated with FVC, TLC, and DLCO at subjects' initial visit and when measured repeatedly over two years. CXCL10 also positively correlated with longitudinal respiratory symptom severity. Additionally, for every log(CXCL10) increase, the risk of longitudinal pulmonary function decline increased 8.8 times over the 5-year study period (95% CI 1.6-50, p = 0.014, log(CXCL0) range 0.84-2.7). In contrast, CXCL9 levels positively correlated with systemic organ involvement at initial study visit (1.5 additional organs involved for every log(CXCL9) increase, 95% CI 1.1-2.0, p = 0.022, log(CXCL9) range 1.3-3.3). CXCL10, not CXCL9, positively correlated with its own blood gene expression and monocyte level. Immunosuppressive treatment was associated with lower levels of both chemokines.
In sarcoidosis subjects, serum CXCL9 levels correlated with systemic organ involvement and CXCL10 levels strongly correlated with respiratory outcomes, which may ultimately prove helpful in clinical management. These differing associations may be due to differences in cellular regulation and tissue origin.
结节病是一种肉芽肿性炎症性疾病，其预后的血液标志物有限。干扰素-γ（IFN-γ）诱导的趋化因子（趋化因子）CXCL9 和 CXCL10 在结节病患者中均增加，但它们具有重要的分子差异。我们的研究旨在确定血清趋化因子是否与疾病严重程度的不同方面相关。
我们使用 ELISA 在结节病患者的初始研究就诊时和纵向测量血清 CXCL9 和 CXCL10 水平。我们检查了这些趋化因子与肺部和器官受累结果、基因表达、外周血免疫细胞群和免疫抑制使用的关系。
更高的 CXCL10 水平与患者初始就诊时的 FVC、TLC 和 DLCO 以及两年内的重复测量呈负相关。CXCL10 还与纵向呼吸症状严重程度呈正相关。此外，每增加一个对数（CXCL10），在 5 年研究期间，纵向肺功能下降的风险增加 8.8 倍（95%CI 1.6-50，p=0.014，log（CXCL0）范围 0.84-2.7）。相比之下，CXCL9 水平与初始研究就诊时的全身器官受累呈正相关（每增加一个对数（CXCL9），涉及 1.5 个额外器官，95%CI 1.1-2.0，p=0.022，log（CXCL9）范围 1.3-3.3）。CXCL10 而不是 CXCL9 与自身血液基因表达和单核细胞水平呈正相关。免疫抑制治疗与两种趋化因子水平降低相关。
在结节病患者中，血清 CXCL9 水平与全身器官受累相关，而 CXCL10 水平与呼吸结局密切相关，这可能最终有助于临床管理。这些不同的关联可能是由于细胞调节和组织起源的差异。
