Abstract
In idiopathic pulmonary fibrosis (IPF), lung accumulation of excessive extracellular iron and macrophage haemosiderin may suggest disordered iron homeostasis leading to recurring microscopic injury and fibrosing damage.
The current study population comprised 89 consistent IPF patients and 107 controls. 54 patients and 11 controls underwent bronchoalveolar lavage (BAL). Haemosiderin was assessed by Perls' stain, BAL fluid malondialdehyde (MDA) by high-performance liquid chromatography, BAL cell iron-dependent oxygen radical generation by fluorimetry and the frequency of hereditary haemochromatosis HFE gene variants by reverse dot blot hybridisation.
Macrophage haemosiderin, BAL fluid MDA and BAL cell unstimulated iron-dependent oxygen radical generation were all significantly increased above controls (p<0.05). The frequency of C282Y, S65C and H63D HFE allelic variants was markedly higher in IPF compared with controls (40.4% versus 22.4%, OR 2.35, p=0.008) and was associated with higher iron-dependent oxygen radical generation (HFE variant 107.4±56.0, HFE wild type (wt) 59.4±36.4 and controls 16.7±11.8 fluorescence units per 105 BAL cells; p=0.028 HFE variant versus HFE wt, p=0.006 HFE wt versus controls).
The data suggest iron dysregulation associated with HFE allelic variants may play an important role in increasing susceptibility to environmental exposures, leading to recurring injury and fibrosis in IPF.
Abstract
HFE gene variants that cause iron-related fibrosing diseases implicate lung iron dysregulation in IPF pathogenesis http://ow.ly/DRnJK
Footnotes
Support statement: The work was supported by a grant from FILAS/Regione Lazio (Italy) to Research and Drug Development (ReDD) Inc., Rome, Italy (a University of Roma Tor Vergata spin-off with which M. Amicosante, F. Mariani and C. Saltini are associated) and the University of Roma Tor Vergata, Rome, Italy; by an unrestricted research grant from the “Associazione Italiana Malattie Interstiziali del Polmone”, Rome, Italy (awarded to M. Losi); by an unrestricted grant from Boehringer Ingelheim; and by a fellowship in memory of Virgilio Guzzini, from the Guzzini family, Recanati, Italy (awarded to M. Amicosante at the inception of the study).
Conflict of interest: Disclosures can be found alongside the online version of this article at erj.ersjournals.com
- Received June 9, 2014.
- Accepted October 25, 2014.
- Copyright ©ERS 2015