Introduction IPF is a progressive disease with a poor prognosis. Recently antifibrotic treatment
with either pirfenidone or nintedanib were approved. Both drugs have been shown to
slow disease progression. In previous studies undertaken before the approval of antifibrotic
treatment we and others have reported on the predictive value of serum CCL18 concentration
in patients not treated with antifibrotics.
Objective To investigate the predictive value of serum CCL18 concentrations on disease progression
and mortality in a cohort of IPF patients treated with antifibrotic drugs. In addition,
we genotyped the CCL18 promoter polymorphism to analyze a correlation between CCL18
concentration and the CCL18 genotype.
Methods IPF was defined according to the ATS/ERS criteria. The study was approved by the
local ethics committee and all 119 patients signed informed consent prior to inclusion.
Serum samples were harvested at initial diagnosis (baseline, prior to antifibrotic
treatment) and during the antifibrotic treatment. Serum CCL18 concentrations were
measured by ELISA. In addition, we genotyped the CCL18 promoter polymorphism (SNP
rs2015086). Patients were followed for 24 months. Pulmonary function tests, including
FVC% and DLCO% and survival status were analyzed.
Results At initial diagnosis the mean CCL18 concentration was 143 ng/ml. In comparison, the
mean CCL18 concentration after 9 ± 4 months of antifibrotic treatment was 156 ng/ml
(p = 0.00 187). The genotyping of the CCL18 promoter polymorphism showed that 69%
of all patients were homozygous (AA-genotype), 30% had a heterozygous (AG-) genotype
and only 1% was homozygous for allele 2 (GG-genotype). The mean CCL18 concentration
in patients with an AA-genotype was 129 ± 46 ng/ml, for patients with AG-genotype
considerably higher with 196 ± 80 ng/ml and for the GG-genotype even higher with 314 ng/ml
(p = 0.0004). Serum CCL18 concentration keeps its predictive value in IPF patients
treated with antifibrotics.
Conclusion Our data show a statistically significant slight increase in the serum CCL18 levels
during an antifibrotic treatment irrespective of the antifibrotic drug. Furthermore,
the CCL18 gene polymorphism has an impact on the CCL18 concentration which also works
for prediction of survival and disease progression in IPF patients treated with antifibrotic
drugs.
