title: Differentiation between acute skin rejection in allotransplantation and T-cell mediated skin inflammation based on gene expression analysis.
abstract: Advances in microsurgical techniques and immunosuppressive medication have rendered transplantation of vascularized composite allografts possible, when autologous tissue is neither available nor sufficient for reconstruction. However, skin rejection and side effects of long-term immunosuppression still remain a major hurdle for wide adoption of this excellent reconstructive technique. Histopathologic changes during acute skin rejection in vascular composite allotransplantation often mimic inflammatory skin disorders and are hard to distinguish. Hence, the identification of diagnostic and therapeutic markers specific for skin rejection is of particular clinical need. Here we present novel markers allowing for early differentiation between rejection in hind limb allotransplantation and contact hypersensitivity. Assessment of Ccl7, Il18, and Il1b expression is most indicative of distinguishing skin rejection from skin inflammatory disorders. Gene expression levels varied significantly across skin types and regions, indicating localization specific mechanism of leukocyte migration and infiltration. Expression of Il12b, Il17a, and Il1b gene expression levels differed significantly between rejection and inflammation, independent of the skin type. In synopsis of the RNA expression profile and previously assessed protein expression, the Il1 family appears as a promising option for accurate skin rejection diagnosis and, as a following step, for development of novel rejection treatments.
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Dolores
authors.initials: D
authors.lastname: Wolfram
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Evi M
authors.initials: EM
authors.lastname: Morandi
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ; Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Nadine
authors.initials: N
authors.lastname: Eberhart
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Theresa
authors.initials: T
authors.lastname: Hautz
authors.affiliation: Division of Bioinformatics, Biocenter, Medical University of Innsbruck, Innrain 80, 6020 Innsbruck, Austria.
authors.forename: Hubert
authors.initials: H
authors.lastname: Hackl
authors.affiliation: Department of Pathology, Medical University of Innsbruck, Muellerstrasse 44, 6020 Innsbruck, Austria.
authors.forename: Bettina
authors.initials: B
authors.lastname: Zelger
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria ; Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Riede
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Tanja
authors.initials: T
authors.lastname: Wachter
authors.affiliation: Department of Dermatology and Venereology, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dubrac
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Ploner
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pierer
authors.affiliation: Department of Visceral, Transplant and Thoracic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schneeberger
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology* / Q000502:physiology; D002465:Cell Movement / Q000276:immunology; D054410:Chemokine CCL7 / Q000276:immunology; D015870:Gene Expression / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006614:Hindlimb / Q000276:immunology / Q000473:pathology; D007165:Immunosuppression Therapy / Q000379:methods; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D007375:Interleukin-1 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D014184:Transplantation, Homologous / Q000379:methods
chemical_list: C515452:Ccl7 protein, rat; D054410:Chemokine CCL7; D007375:Interleukin-1; D020382:Interleukin-18