Soluble CD59 is a novel biomarker for the prediction of obstructive chronic lung allograft dysfunction after lung transplantation

Budding, Kevin; van de Graaf, Eduard. A.; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M.; Luijk, Bart D.; Oudijk, Erik-Jan D.; van Kessel, Diana A.; Grutters, Jan C.; Hack, C. Erik; Otten, Henderikus G.

doi:10.1038/SREP26274

Title

Soluble CD59 is a novel biomarker for the prediction of obstructive chronic lung allograft dysfunction after lung transplantation

Author

Budding, Kevin

van de Graaf, Eduard. A.

Kardol-Hoefnagel, Tineke

Kwakkel-van Erp, Johanna M.

Luijk, Bart D.

Oudijk, Erik-Jan D.

van Kessel, Diana A.

Grutters, Jan C.

Hack, C. Erik

Otten, Henderikus G.

Abstract

CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers = 400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers = 400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

Language

English

Source (journal)

Scientific reports. - London, 2011, currens

Publication

London : Nature Publishing Group , 2016

ISSN

2045-2322

DOI

10.1038/SREP26274

Volume/pages

6 (2016) , 7 p.