A prospective study on serum Cytokeratin (CK)-18 and CK18 fragments as biomarkers of acute hepato-intestinal GVHD
Apoptotic intestinal crypt cells are pathognomonic of acute intestinal graft versus host disease (GVHD). Serum levels of the apoptotic degradation product cytokeratin-18 fragments (CK18F) were associated with acute hepato-intestinal GVHD. Here we present a prospective clinical observational trial (N...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
27 June 2018
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| In: |
Leukemia
Year: 2018, Volume: 32, Issue: 12, Pages: 2685-2692 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-018-0183-0 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1038/s41375-018-0183-0 Verlag, Volltext: https://www.nature.com/articles/s41375-018-0183-0 
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| Author Notes: | Sandra Sauer, Johannes Hüsing, Jacek Hajda, Frank Neumann, Aleksandar Radujkovic, Anthony D. Ho, Peter Dreger, Thomas Luft |
| Summary: | Apoptotic intestinal crypt cells are pathognomonic of acute intestinal graft versus host disease (GVHD). Serum levels of the apoptotic degradation product cytokeratin-18 fragments (CK18F) were associated with acute hepato-intestinal GVHD. Here we present a prospective clinical observational trial (NCT00935324) investigating serum levels of total CK18 (tCK18) and apoptotic CK18F to predict imminent acute hepato-intestinal GVHD and response to treatment. Total (t)CK18 and CK18F kinetics were measured before transplantation and in weekly intervals thereafter. In total 109 patients were enrolled. Acute hepato-intestinal GVHD grade I-IV was suspected in 36 patients (33%) at a median of 56 days post-transplant, 12 of these patients developed steroid-refractory GVHD. Both tCK18 and apoptotic CK18F increased at GVHD onset, and distinguished patients with suspected acute hepato-intestinal GVHD who were negative in intestinal histology. In patients with clinical acute hepato-intestinal GVHD, tCK18 significantly raised already 7-14 days before symptom onset. In receiver operator characteristics, areas under the curve at GVHD onset were 0.927 (p < 0.001) for tCK18 and 0.875 (p < 0.001) for apoptotic CK18F for patients with proven hepato-intestinal acute GVHD. This prospective study validates CK18F and highlights tCK18 as specific biomarkers suitable for improving prediction and diagnosis of suspected imminent and clinically manifest acute hepato-intestinal GVHD. |
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| Item Description: | Gesehen am 22.05.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-018-0183-0 |