Caliskan Canay, Seeliger Benjamin, Jäger Benedikt, Fuge Jan, Welte Tobias, Terwolbeck Oliver, Freise Julia, van Moorsel Coline H M, Zhang Yingze, Prasse Antje
Department of Respiratory Medicine, Hannover Medical School and Biomedical Research in End-stage and Obstructive Lung Disease Hannover, German Lung Research Center (DZL), 30265 Hannover, Germany.
Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany.
J Clin Med. 2020 Jun 25;9(6):1993. doi: 10.3390/jcm9061993.
Idiopathic pulmonary fibrosis (IPF) is a progressive disease with high mortality. CC-chemokine ligand 18 (CCL18) is predictive of survival in IPF. We described correlation of CCL18 serum levels with the genotype of C > T polymorphism the -gene, which was associated with survival in a pre-antifibrotic cohort (Part-A). Herein (Part-B), we aimed to validate these findings and to study the effects of antifibrotics. Two cohorts were prospectively recruited, cohort-A ( = 61, pre-antifibrotic) and cohort B ( = 101, received antifibrotics). Baseline CCL18 serum level measurement by enzyme-linked immunosorbent assay (ELISA, serially in cohort B) and genotyping of was performed and correlated with clinical outcomes. The CT genotype was present in 15% and 31% of patients. These patients had higher CCL18 levels compared to the TT-genotype (cohort-A: 234 vs. 115.8 ng/mL, < 0.001; cohort B: 159.5 vs. 120 ng/mL, = 0.0001). During antifibrotic therapy, CCL18 increased ( = 0.0036) regardless of -genotype and antifibrotic-agent. In cohort-A, baseline CCL18-cutoff (>120 ng/mL) and CT-genotype were associated with mortality ( = 0.041 and = 0.0051). In cohort-B, the CCL18-cutoff (>140 ng/mL) was associated with mortality ( = 0.003) and progression ( = 0.004), but not the CT/CC-genotype. In conclusion, we validated the correlation between -genotype and CCL18 serum levels, which was predictive of (progression-free)-survival in two prospective validation cohorts.
特发性肺纤维化（IPF）是一种死亡率高的进行性疾病。CC趋化因子配体18（CCL18）可预测IPF患者的生存情况。我们描述了CCL18血清水平与-基因C>T多态性基因型的相关性，该基因在一个抗纤维化治疗前队列中与生存相关（A部分）。在此（B部分），我们旨在验证这些发现并研究抗纤维化药物的作用。前瞻性招募了两个队列，队列A（n = 61，抗纤维化治疗前）和队列B（n = 101，接受抗纤维化治疗）。通过酶联免疫吸附测定（ELISA，队列B中进行连续检测）测量基线CCL18血清水平，并进行基因分型，将其与临床结局相关联。CT基因型在15%和31%的患者中存在。与TT基因型患者相比，这些患者的CCL18水平更高（队列A：234 vs. 115.8 ng/mL，P < 0.001；队列B：159.5 vs. 120 ng/mL，P = 0.0001）。在抗纤维化治疗期间，无论-基因型和抗纤维化药物如何，CCL18均升高（P = 0.0036）。在队列A中，基线CCL18临界值（>120 ng/mL）和CT基因型与死亡率相关（P = 0.041和P = 0.0051）。在队列B中，CCL18临界值（>140 ng/mL）与死亡率（P = 0.003）和疾病进展（P = 0.004）相关，但与CT/CC基因型无关。总之，我们验证了-基因型与CCL18血清水平之间的相关性，其可预测两个前瞻性验证队列中的（无进展）生存情况。
