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.
Highlights
CD59 is a membrane anchored complement regulatory protein that inhibits membrane attack complex (MAC) formation, thereby preventing complement mediated cell lysis[1,2]
Long-term outcome after LTx is hampered by chronic lung allograft dysfunction (CLAD) which can be divided into an obstructive CLAD and a restrictive CLAD
80% of the bronchiolitis obliterans syndrome (BOS) patients have elevated soluble form of CD59 (sCD59) serum concentrations compared to the median of matched controls
Summary
CD59 is a membrane anchored complement regulatory protein that inhibits membrane attack complex (MAC) formation, thereby preventing complement mediated cell lysis[1,2]. Elevated circulating sCD59 concentrations have been found in acute myocardial infarction[10], and higher serum titers of glycated sCD59 have been described in diabetes mellitus[12]. Despite these findings, the role of sCD59 and its association with disease is still largely unidentified. In the clinical setting the FEV1 decrease is used as surrogate marker and will occur after obliterative bronchiolitis has already developed The recognition of this damage and the diagnosis obliterative bronchiolitis prior to BOS development may be of help in designing therapies for BOS prevention. Five years after LTx the BOS-free survival is 50%, though most patients who survive short-term complications, will eventually develop BOS14
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