A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis

Liv I B Sikkeland; Thor Ueland; May B Lund; Michael Thomas Durheim; Tom Eirik Mollnes

doi:10.3389/fmed.2023.1236495

A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis

Front Med (Lausanne). 2023 Aug 9:10:1236495. doi: 10.3389/fmed.2023.1236495. eCollection 2023.

Authors

Liv I B Sikkeland^{1

2}, Thor Ueland^{1

3

4}, May B Lund^{1

2}, Michael Thomas Durheim^{1

2}, Tom Eirik Mollnes^{4

5

6

7}

Affiliations

¹ Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
² Department of Respiratory Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
³ Institute of Internal Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway.
⁴ K. G. Jebsen, Thrombosis Research Center, University of Tromsø, Tromsø, Norway.
⁵ Department of Immunology, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway.
⁶ Research Laboratory, Nordland Hospital, Bodø, Norway.
⁷ Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease characterized by damage to the alveolar epithelium, leading to fibrosis and excessive accumulation of extracellular matrix in the interstitium of the lung. In the present study we performed high-resolution proteomic profiling of bronchoalveolar lavage (BAL) from IPF patients and controls, and found that the complement pathway was highly upregulated in IPF. The proteins C5, C6, C7, C8, and C9, all of which are part of the complement end product, TCC, were all upregulated. We also found that TCC levels were increased in plasma among IPF patients compared to controls, after adjustment for age, sex and BMI [mean (SD) 0.62 (0.24) vs. 0.33 (0.10), p = 0.031]. These findings suggest a role for the complement system in the pathogenesis of IPF.

Keywords: bronchial lavage fluid; idiopathic pulmonary fibrosis; interstitial lung disease; proteomics; terminal complement complex.