IL-4 polymorphisms, HRCT score and lung tissue markers in idiopathic pulmonary fibrosis

Hum Immunol. 2013 Oct;74(10):1346-51. doi: 10.1016/j.humimm.2013.07.011. Epub 2013 Jul 31.

Abstract

Aims: We studied the influence of IL-4 gene polymorphisms on the IPF phenotype, i.e., extent of radiological changes (HRCT interstitial (IS) and alveolar (AS) score) and histopathological markers from lung biopsies.

Patients and methods: 46 IPF patients underwent genotyping, 43 of them had HRCT and 14 patients had a surgical lung biopsy. The HRCT scans were evaluated for AS and IS. The histopathological evaluation comprised myofibroblast foci (MF), intensity of inflammation and fibrosis (Ashcroft score) and numbers of eosinophils and granulomas. For immunohistochemical evaluation primary antibodies against PAR-2, CD124, TGF beta, YY-1 and TSLP were used. The IL-4 and IL-4 R alpha gene polymorphisms were characterized.

Results: We found a correlation between eosinophils in lung biopsies and AS. The Ashcroft score was higher in IL-4 HA 2 GCC and MF were more frequent in IL-4 HA 2 TCC carriers. A relationship was found between IL-4 (-1098) A2 T and PAR-2 expression and IL-4 (-590) A1 T, IL-4 HA1TTT and CD124 expression. AS was lower in IL-4 (-590) A1 C, in IL-4 HA1 TCC and in IL-4RA (+1902) A1 A carriers.

Conclusions: We suggest that the polymorphisms of IL-4 genes might influence the phenotype of IPF reflected by histopathological changes in lung biopsies and HRCT score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Biomarkers
  • Biopsy
  • Eosinophils / metabolism
  • Female
  • Genotype
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnosis*
  • Idiopathic Pulmonary Fibrosis / genetics*
  • Interleukin-4 / genetics*
  • Interleukin-4 Receptor alpha Subunit / genetics
  • Interleukin-4 Receptor alpha Subunit / metabolism
  • Leukocyte Count
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Genetic*

Substances

  • Biomarkers
  • Interleukin-4 Receptor alpha Subunit
  • Interleukin-4