title: Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.
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.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kevin
authors.initials: K
authors.lastname: Budding
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Eduard A
authors.initials: EA
authors.lastname: van de Graaf
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Tineke
authors.initials: T
authors.lastname: Kardol-Hoefnagel
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Kwakkel-van Erp
authors.affiliation: Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Bart D
authors.initials: BD
authors.lastname: Luijk
authors.affiliation: Center of Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Erik-Jan D
authors.initials: ED
authors.lastname: Oudijk
authors.affiliation: Center of Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Diana A
authors.initials: DA
authors.lastname: van Kessel
authors.affiliation: Center of Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.|Departments of Rheumatology and Dermatology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Henderikus G
authors.initials: HG
authors.lastname: Otten
mesh_terms: D000293:Adolescent; D000328:Adult; D064591:Allografts; D015415:Biomarkers / Q000097:blood; D001989:Bronchiolitis Obliterans / Q000097:blood* / Q000209:etiology* / Q000276:immunology; D018957:CD59 Antigens / Q000097:blood*; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000209:etiology / Q000276:immunology; D006801:Humans; D053208:Kaplan-Meier Estimate; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012307:Risk Factors; D012995:Solubility; D013997:Time Factors; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018957:CD59 Antigens; C051590:CD59 protein, human