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Differentiation between acute skin rejection in allotransplantation and T-cell mediated skin inflammation based on gene expression analysis.

Wolfram D, Morandi EM, Eberhart N, Hautz T, Hackl H, Zelger B, Riede G, Wachter T, Dubrac S, Ploner C, Pierer G, Schneeberger S - Biomed Res Int (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

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.

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Related in: MedlinePlus

Histological evaluation of skin samples. Representative microscopic images of hematoxylin and eosin stained histological skin sections: (a) contact hypersensitivity (CHS) reaction (pinna, 24 h), (A) control skin from left pinna, (b) skin rejection (grade 2, thigh, POD 5); (c) delayed type hypersensitivity (DTH) reaction (planta pedis, 24 h), (C) control skin from left footpad, and (d) skin rejection (grades 1-2, planta pedis) are presented.
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fig2: Histological evaluation of skin samples. Representative microscopic images of hematoxylin and eosin stained histological skin sections: (a) contact hypersensitivity (CHS) reaction (pinna, 24 h), (A) control skin from left pinna, (b) skin rejection (grade 2, thigh, POD 5); (c) delayed type hypersensitivity (DTH) reaction (planta pedis, 24 h), (C) control skin from left footpad, and (d) skin rejection (grades 1-2, planta pedis) are presented.

Mentions: On POD 5, 40% of the animals displayed grade I rejection and 60% grade II rejection. The CHS and DTH animals showed a most impressive erythema and swelling 24 hours after challenge (Figure 1). Skin biopsies taken from thigh and footpad from allografts at POD 5 exhibited an almost identical composition and distribution of inflammatory cells when compared with CHS and DTH at 24 hours after challenge. Histological evaluation showed a moderate to severe perivascular inflammation with or without mild epidermal and/or adnexal epidermal dyskeratosis or apoptosis consistent with rejection grade II in 80% of the biopsies taken from thigh and footpad in the rejection group (ATC). 24 hours after challenge with DTH, animals presented with a moderate to severe inflammatory response mainly located in the epidermis as well as an interphase reaction, correlating with grade II rejection. The same histological finding was found in the CHS group, and 50% of the animals, however, showed progression to a severe inflammatory response, correlating with grade III rejection (Figure 2).


Differentiation between acute skin rejection in allotransplantation and T-cell mediated skin inflammation based on gene expression analysis.

Wolfram D, Morandi EM, Eberhart N, Hautz T, Hackl H, Zelger B, Riede G, Wachter T, Dubrac S, Ploner C, Pierer G, Schneeberger S - Biomed Res Int (2015)

Histological evaluation of skin samples. Representative microscopic images of hematoxylin and eosin stained histological skin sections: (a) contact hypersensitivity (CHS) reaction (pinna, 24 h), (A) control skin from left pinna, (b) skin rejection (grade 2, thigh, POD 5); (c) delayed type hypersensitivity (DTH) reaction (planta pedis, 24 h), (C) control skin from left footpad, and (d) skin rejection (grades 1-2, planta pedis) are presented.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4338383&req=5

fig2: Histological evaluation of skin samples. Representative microscopic images of hematoxylin and eosin stained histological skin sections: (a) contact hypersensitivity (CHS) reaction (pinna, 24 h), (A) control skin from left pinna, (b) skin rejection (grade 2, thigh, POD 5); (c) delayed type hypersensitivity (DTH) reaction (planta pedis, 24 h), (C) control skin from left footpad, and (d) skin rejection (grades 1-2, planta pedis) are presented.
Mentions: On POD 5, 40% of the animals displayed grade I rejection and 60% grade II rejection. The CHS and DTH animals showed a most impressive erythema and swelling 24 hours after challenge (Figure 1). Skin biopsies taken from thigh and footpad from allografts at POD 5 exhibited an almost identical composition and distribution of inflammatory cells when compared with CHS and DTH at 24 hours after challenge. Histological evaluation showed a moderate to severe perivascular inflammation with or without mild epidermal and/or adnexal epidermal dyskeratosis or apoptosis consistent with rejection grade II in 80% of the biopsies taken from thigh and footpad in the rejection group (ATC). 24 hours after challenge with DTH, animals presented with a moderate to severe inflammatory response mainly located in the epidermis as well as an interphase reaction, correlating with grade II rejection. The same histological finding was found in the CHS group, and 50% of the animals, however, showed progression to a severe inflammatory response, correlating with grade III rejection (Figure 2).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria.

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.

Show MeSH
Related in: MedlinePlus