Lung

, Volume 188, Issue 6, pp 475–481 | Cite as

Fcγ Receptor IIIb (CD16b) Polymorphisms are Associated with Susceptibility to Idiopathic Pulmonary Fibrosis

  • Stylianos Bournazos
  • Irini Bournazou
  • John T. Murchison
  • William A. Wallace
  • Pauline McFarlane
  • Nikhil Hirani
  • A. John Simpson
  • Ian Dransfield
  • Simon P. Hart
Article

Abstract

An excess of neutrophils in the alveoli and lung interstitium has been described in idiopathic pulmonary fibrosis (IPF). Engagement of neutrophil Fcγ receptors with IgG complexes may contribute to the pathogenesis of IPF. The neutrophil FcγRIIIb receptor occurs in two codominantly expressed allelic variants, NA1 and NA2, which exhibit different binding affinities for IgG1 and IgG3 subclasses. The aim of this study was to investigate whether FcγRIIIb genotype is associated with IPF susceptibility or disease progression. In a case-control study we compared the distribution of FcγRIIIb NA1/2 polymorphisms in 142 patients with IPF and in 218 controls using allele-specific PCR amplification. Significant skewing in the distribution of FcγRIIIb genotypes was observed between patients with IPF and control subjects. In the IPF cohort, there was higher frequency of the NA1/NA1 genotype (0.19 vs. 0.07), and lower NA2/NA2 frequency (0.31 vs. 0.50; χ2 = 17.71, df = 2, P < 0.001). The overall frequency of the NA1 allele was increased in IPF patients compared to controls (0.44 vs. 0.29; P < 0.0001, odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.42–2.64). Heterozygotes and homozygotes of the NA1 allele were at higher risk of developing IPF (OR = 2.19, 95% CI = 1.40–3.41, P = 0.0005), whereas the NA2 allele was protective against IPF (OR = 0.34, 95% CI = 0.17–0.65, P = 0.0014). There was no association of FcγRIIIb genotype with disease progression as assessed by serial lung function measurements. FcγRIIIb NA1/2 polymorphisms are associated with IPF disease susceptibility. These results support a role for immunological mechanisms contributing to IPF pathogenesis.

Keywords

Fc receptors Idiopathic pulmonary fibrosis Interstitial lung disease Neutrophils 

Notes

Acknowledgments

We are grateful to Dr. Andrew Robson for his help in obtaining lung function measurements and Dr. Zhe Hui Hoo for his help and comments. We also thank all the past members from our group (Centre for Inflammation Research, UK) and all the subjects who participated in this study. This work was supported by grants from the British Heart Foundation (FS/05/119/19568) and the Medical Research Council.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Stylianos Bournazos
    • 1
    • 2
  • Irini Bournazou
    • 1
  • John T. Murchison
    • 3
  • William A. Wallace
    • 1
    • 4
  • Pauline McFarlane
    • 5
  • Nikhil Hirani
    • 1
    • 5
  • A. John Simpson
    • 1
    • 5
  • Ian Dransfield
    • 1
  • Simon P. Hart
    • 6
  1. 1.University of Edinburgh/Medical Research Council Centre for Inflammation Research, The Queen’s Medical Research InstituteEdinburghUK
  2. 2.Centre for Cardiovascular ScienceQueen’s Medical Research Institute, University of EdinburghEdinburghUK
  3. 3.Department of RadiologyRoyal Infirmary of EdinburghEdinburghUK
  4. 4.Department of PathologyRoyal Infirmary of EdinburghEdinburghUK
  5. 5.Respiratory Medicine UnitRoyal Infirmary of EdinburghEdinburghUK
  6. 6.Division of Cardiovascular and Respiratory StudiesHull York Medical School/University of HullCottinghamUK

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