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

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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.

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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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Authors and Affiliations

  1. University of Edinburgh/Medical Research Council Centre for Inflammation Research, The Queen’s Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK

    Stylianos Bournazos, Irini Bournazou, William A. Wallace, Nikhil Hirani, A. John Simpson & Ian Dransfield

  2. Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

    Stylianos Bournazos

  3. Department of Radiology, Royal Infirmary of Edinburgh, Edinburgh, UK

    John T. Murchison

  4. Department of Pathology, Royal Infirmary of Edinburgh, Edinburgh, UK

    William A. Wallace

  5. Respiratory Medicine Unit, Royal Infirmary of Edinburgh, Edinburgh, UK

    Pauline McFarlane, Nikhil Hirani & A. John Simpson

  6. Division of Cardiovascular and Respiratory Studies, Hull York Medical School/University of Hull, Cottingham, UK

    Simon P. Hart

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  1. Stylianos Bournazos
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Correspondence to Stylianos Bournazos.

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Bournazos, S., Bournazou, I., Murchison, J.T. et al. Fcγ Receptor IIIb (CD16b) Polymorphisms are Associated with Susceptibility to Idiopathic Pulmonary Fibrosis. Lung 188, 475–481 (2010). https://doi.org/10.1007/s00408-010-9262-3

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  • DOI: https://doi.org/10.1007/s00408-010-9262-3

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