Respiratory Diseases Unit, Department of Medical and Surgical Sciences & Neurosciences, Siena University Hospital, Siena, Tuscany 53100, Italy.
Rheumatology Unit, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Tuscany 53100, Italy.
Tissue Cell. 2024 Oct;90:102516. doi: 10.1016/j.tice.2024.102516. Epub 2024 Aug 3.
Novel progressive fibrotic phenotype has recently been proposed characterized by progressive and inexorable worsening of the disease. Krebs von den Lungen-6 (KL-6) has been proposed as fibrotic-ILD biomarker. We aimed to assess the role of KL-6 in fibrotic-ILD and the progressive phenotype in accordance with serial serum KL-6.
107 patients were enrolled in the study (median age,IQR, 65(54-71)y/o) followed at respiratory diseases and rheumatology units of University of Siena. Thirty-five had diagnoses of IPF, 18 sarcoidosis, 10 PLCH, 5 LAM, 24 fibrotic HP(fHP), 13 RA (4/13 RA-ILD) and 22 SSc (18/22 SSc-ILD). Serial serum samples were collected before therapy (t0) and 24 months later (t1) from IPF, SSc- and RA-ILD patients. Twenty-two healthy controls (HC) were enrolled. Serum samples were assayed for KL-6 concentrations (Fujirebio Europe, Gent, Belgium).
Higher KL-6 concentrations were reported in IPF, fHP and SSc-ILD patients than HC (p<0.0001). KL-6 cut-off value of 885 U/mL identified fibrotic-ILD patients. Logistic regression analysis indicated KL-6 (p=0.004) and smoking-habit (p=0.005) affected the ILD diagnosis. The decision tree model showed KL-6>1145 U/mL, DLco≤60.15 %, FVC≤86 % to classify 86 % IPF patients. Inverse correlation between T0-KL-6 and T1-FVC%(r=-0.314, p=0.046) and T1-DLco%(r=-0.327, p=0.038) in the progressive group.
KL-6 proved to be a reliable marker for diagnosis and prognosis of fibrotic ILD patients with predictive value in progressive fibrotic patients and a useful marker to identify the new and similar progressive phenotype of IPF and SSc-ILD patients assessing the functional progression in accordance with serial serum KL-6 measurements.
最近提出了一种新的进行性纤维化表型，其特征为疾病的进行性和不可避免的恶化。Krebs von den Lungen-6（KL-6）被提议作为纤维化间质性肺病（ILD）的生物标志物。我们旨在根据连续血清 KL-6 评估 KL-6 在纤维化 ILD 和进行性表型中的作用。
本研究纳入了 107 名患者（中位年龄，IQR，65（54-71）岁），在锡耶纳大学的呼吸疾病和风湿病科接受随访。其中 35 例诊断为特发性肺纤维化（IPF），18 例为结节病，10 例为机化性肺炎（PLCH），5 例为淋巴管平滑肌瘤病（LAM），24 例为纤维化性特发性肺高压（fHP），13 例为类风湿关节炎（RA）（4/13 例 RA-ILD），22 例为系统性硬化症（SSc）（18/22 例 SSc-ILD）。在治疗前（t0）和 24 个月后（t1），从 IPF、SSc-ILD 和 RA-ILD 患者中采集了连续的血清样本。纳入了 22 名健康对照者（HC）。用 Fujirebio Europe（比利时根特）的试剂盒检测血清 KL-6 浓度。
与 HC 相比，IPF、fHP 和 SSc-ILD 患者的 KL-6 浓度更高（p<0.0001）。KL-6 的截断值为 885 U/mL，可识别出纤维化 ILD 患者。Logistic 回归分析表明 KL-6（p=0.004）和吸烟习惯（p=0.005）影响 ILD 诊断。决策树模型显示 KL-6>1145 U/mL、DLco≤60.15%、FVC≤86%，可对 86%的 IPF 患者进行分类。在进行性组中，T0-KL-6 与 T1-FVC%（r=-0.314，p=0.046）和 T1-DLco%（r=-0.327，p=0.038）之间存在负相关。
KL-6 被证明是纤维化 ILD 患者诊断和预后的可靠标志物，在进行性纤维化患者中具有预测价值，是一种有用的标志物，可通过连续血清 KL-6 测量来识别 IPF 和 SSc-ILD 患者的新的类似进行性表型，评估与 KL-6 相关的功能进展。
