title: Epidermal elafin expression is an indicator of poor prognosis in cutaneous graft-versus-host disease.
abstract: Graft-versus-host disease (GVHD) remains a common and potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation. In the skin, GVHD can present in an acute (aGVHD), chronic lichenoid (clGVHD), or chronic sclerotic form (csGVHD). Measuring peripheral blood levels of the keratinocyte-derived protease inhibitor elafin has recently emerged as a promising tool for the diagnosis of cutaneous aGVHD. We evaluated whether the analysis of elafin expression in skin would allow distinguishing aGVHD from drug hypersensitivity rashes (DHR) and whether cutaneous elafin expression would correlate with disease severity or altered prognosis of aGVHD and clGVHD/csGVHD. Skin biopsies from aGVHD (n=22), clGVHD (n=15), csGVHD (n=7), and DHR (n=10) patients were collected and epidermal elafin expression and its association with diverse clinical/histological parameters were analyzed. Acute GVHD and DHR displayed varying degrees of elafin expression. No elafin was detectable in csGVHD, whereas the molecule was increased in clGVHD as compared with aGVHD. Elafin-high aGVHD/clGVHD lesions presented with epidermal thickening and were associated with poor prognosis-i.e., decreased overall survival in aGVHD and corticosteroid resistance in clGVHD. Although cutaneous elafin does not seem to discriminate aGVHD from DHR lesions, our study strongly suggests an association between cutaneous elafin expression and poor prognosis for patients with cutaneous GVHD.
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Marie-Charlotte
authors.initials: MC
authors.lastname: Brüggen
authors.affiliation: Skin and Endothelium Research Division, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Petzelbauer
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Dragana
authors.initials: D
authors.lastname: Jankovic
authors.affiliation: Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: French
authors.affiliation: Department of Hematology/Transplantation, AP-HP Hospital Saint Louis, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Rabitsch
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kuzmina
authors.affiliation: Bone Marrow Transplantation Unit, Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Kalhs
authors.affiliation: Division of General Dermatology, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Knobler
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Stingl
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases, Department of Dermatology, Medical University of Vienna, Vienna, Austria. Electronic address: georg.stary@meduniwien.ac.at.
authors.forename: Georg
authors.initials: G
authors.lastname: Stary
mesh_terms: D000328:Adult; D001706:Biopsy; D015331:Cohort Studies; D053492:Elafin / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000473:pathology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053492:Elafin; C506806:PI3 protein, human; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha