Department of Rheumatology, Ren Ji Hospital South Campus, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Department of Pulmonology, Ren Ji Hospital South Campus, Shanghai Jiaotong University School of Medicine, Shanghai, P.R. China.
Rheumatology (Oxford). 2019 Mar 1;58(3):511-521. doi: 10.1093/rheumatology/key341.
There is an unmet need for the development of new biomarkers for idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD).
Peripheral CD4+CXCR4+ T cells, stromal cell-derived factor-1 and Krebs von den Lungen-6 were measured in patients with IIM-ILD (n = 85) and controls. The relation to pulmonary functions, high-resolution CT scores, specific clinical phenotypes and survival was analysed. Cytokine-expression profiling of these CD4+CXCR4+ T cells and their co-culture with pulmonary fibroblasts were conducted.
The peripheral percentages of CD4+CXCR4+ T cells were significantly elevated in IIM-ILD patients, and correlated with high-resolution CT score (r = 0.7136, P < 0.0001) and pulmonary function impairments, such as percentage of forced volume vital capacity (r = -0.4734, P = 0.0005). They were associated with anti-melanoma differentiation-associated gene 5 autoantibodies and the amyopathic DM phenotype. In IIM-ILD, peripheral percentages of CD4+CXCR4+ T cells ⩾30% revealed a 6-month mortality as high as 47%. These CD4+CXCR4+ T cells express high levels of IL-21 and IL-6. In vitro blockade of IL-21 signalling by neutralization of IL-21 or Janus kinase inhibitor could abolished the fibroblast proliferation.
Overall, peripheral CD4+CXCR4+ T cells appear to be a potentially valuable novel biomarker associated with the severity and prognosis of IIM-ILD. They promote pulmonary fibroblast proliferation via IL-21, which may herald future targeted treatments for this severe disease.
特发性炎症性肌病相关间质性肺病（IIM-ILD）新生物标志物的开发仍存在未满足的需求。
测量了 85 例 IIM-ILD 患者和对照组患者外周血 CD4+CXCR4+T 细胞、基质细胞衍生因子-1 和 Krebs von den Lungen-6。分析了它们与肺功能、高分辨率 CT 评分、特定临床表型和生存的关系。对这些 CD4+CXCR4+T 细胞进行了细胞因子表达谱分析，并与肺成纤维细胞进行了共培养。
IIM-ILD 患者外周血 CD4+CXCR4+T 细胞的百分比明显升高，与高分辨率 CT 评分（r = 0.7136，P < 0.0001）和肺功能损害（如用力肺活量百分比，r = -0.4734，P = 0.0005）相关。它们与抗黑色素瘤分化相关基因 5 自身抗体和无肌病性 DM 表型相关。在 IIM-ILD 中，外周血 CD4+CXCR4+T 细胞百分比 ⩾30%提示 6 个月死亡率高达 47%。这些 CD4+CXCR4+T 细胞表达高水平的白细胞介素-21 和白细胞介素-6。通过中和白细胞介素-21 或 Janus 激酶抑制剂阻断白细胞介素-21 信号通路，可消除成纤维细胞增殖。
总之，外周血 CD4+CXCR4+T 细胞似乎是一种与 IIM-ILD 严重程度和预后相关的潜在有价值的新型生物标志物。它们通过白细胞介素-21 促进肺成纤维细胞增殖，可能预示着未来针对这种严重疾病的靶向治疗。
