Genetic Variation in CCL18 Gene Influences CCL18 Expression and Correlates with Survival in Idiopathic Pulmonary Fibrosis-Part B.

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.