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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4535-4542.
Prepublished online as a Blood First Edition Paper on August 16, 2007; DOI 10.1182/blood-2006-10-049817.


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Submitted October 13, 2006
Accepted June 26, 2007

Serum cytokeratin-18 fragments as quantitative markers of epithelial apoptosis in liver and intestinal graft-versus-host disease

Thomas Luft*, Michael Conzelmann, Axel Benner, Michael Rieger, Michael Hess, Ulrich Strohhaecker, Martin Gorner, Ute Hegenbart, Anthony D. Ho, and Peter Dreger

Dept. Medicine V, University of Heidelberg, Heidelberg, Germany
Unit Adaptive Immune Regulation, German Cancer Research Center, Heidelberg, Germany
Department of Biostatistics, German Cancer Research Center, Heidelberg, Germany

* Corresponding author; email: t.luft{at}dkfz.de.

Graft-versus-host disease (GvHD) is the main complication of allogeneic stem cell transplantation. However, diagnosis of GvHD and evaluation of response to immuno-suppressive treatment is sometimes difficult. Since apoptosis is the histopathological hallmark in GvHD, we investigated whether active GvHD-induced target organ destruction is mirrored by serum levels of the caspase-cleaved neo-epitope of cytokeratin 18 fragments (CK18F). Serum CK18F kinetics was monitored by M30 antibody-based ELISA in 50 patients who fulfilled histopathological and/or clinical criteria diagnostic for GvHD. Both intestinal and hepatic GvHD were consistently associated with significant elevations of CK18F levels over baseline. Responses of GvHD to immunosuppressive therapy were paralleled by CK18F decreases, whereas resistant GvHD was characterized by persistent CK18F rises. Clinical conditions that might represent relevant differential diagnoses, such as toxic mucositis, non-complicated, infection-related diarrhea and veno-occlusive disease were not associated with CK18F elevations. In conclusion, CK18F monitoring provides a serum marker for quantitative assessment of GvHD-associated apoptotic activity in intestinal and hepatic GvHD. Although apoptosis is not GvHD-specific, CK18F may help to distinguish active GvHD from GvHD-unrelated conditions with similar symptoms, and to monitor response to immunosuppressive treatment. Prospective studies are warranted to evaluate how CK18F may assist in diagnosis, grading, and treatment guidance of GvHD.


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