Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation

T. Hautz; B. Zelger; J. Grahammer; C. Krapf; A. Amberger; G. Brandacher; L. Landin; H. Müller; M. P. Schön; P. Cavadas; A. W.P. Lee; J. Pratschke; R. Margreiter; S. Schneeberger

doi:10.1111/j.1600-6143.2010.03075.x

Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation

T. Hautz, B. Zelger, J. Grahammer, C. Krapf, A. Amberger, G. Brandacher, L. Landin, H. Müller, M. P. Schön, P. Cavadas, A. W.P. Lee, J. Pratschke, R. Margreiter, S. Schneeberger

Research output: Contribution to journal › Article › peer-review

61 Scopus citations

Abstract

Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

Original language	English (US)
Pages (from-to)	1200-1209
Number of pages	10
Journal	American Journal of Transplantation
Volume	10
Issue number	5
DOIs	https://doi.org/10.1111/j.1600-6143.2010.03075.x
State	Published - May 2010
Externally published	Yes

Keywords

Adhesion molecules
Composite tissue allograft
Composite tissue transplantation
Hand transplantation
Lymphocyte trafficking
Rat
Rejection
Selectin ligand inhibition
Skin
Topical therapy

ASJC Scopus subject areas

Immunology and Allergy
Transplantation
Pharmacology (medical)

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10.1111/j.1600-6143.2010.03075.x

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Hautz, T., Zelger, B., Grahammer, J., Krapf, C., Amberger, A., Brandacher, G., Landin, L., Müller, H., Schön, M. P., Cavadas, P., Lee, A. W. P., Pratschke, J., Margreiter, R., & Schneeberger, S. (2010). Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation. American Journal of Transplantation, 10(5), 1200-1209. https://doi.org/10.1111/j.1600-6143.2010.03075.x

Hautz, T, Zelger, B, Grahammer, J, Krapf, C, Amberger, A, Brandacher, G, Landin, L, Müller, H, Schön, MP, Cavadas, P, Lee, AWP, Pratschke, J, Margreiter, R & Schneeberger, S 2010, 'Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation', American Journal of Transplantation, vol. 10, no. 5, pp. 1200-1209. https://doi.org/10.1111/j.1600-6143.2010.03075.x

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title = "Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation",

abstract = "Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.",

keywords = "Adhesion molecules, Composite tissue allograft, Composite tissue transplantation, Hand transplantation, Lymphocyte trafficking, Rat, Rejection, Selectin ligand inhibition, Skin, Topical therapy",

author = "T. Hautz and B. Zelger and J. Grahammer and C. Krapf and A. Amberger and G. Brandacher and L. Landin and H. M{\"u}ller and Sch{\"o}n, {M. P.} and P. Cavadas and Lee, {A. W.P.} and J. Pratschke and R. Margreiter and S. Schneeberger",

note = "Funding Information: This work was done as part of the cooperation program between the Serbian Academy of Sciences and Arts and the Institute for the Problems of Material Science of the National Academy of Sciences of the Ukraine, i.e. as part of the project {\textquoteleft}Synthesis of functional materials in accordance with the synthesis-structure-properties-application relationship{\textquoteright} financed by the Ministry for Science and Technology of Serbia, and partially through NEDO International Joint Research Grant Program: “Wetability of solid by liquid at high temperatures”. ",

year = "2010",

month = may,

doi = "10.1111/j.1600-6143.2010.03075.x",

language = "English (US)",

volume = "10",

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T1 - Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation

AU - Hautz, T.

AU - Zelger, B.

AU - Grahammer, J.

AU - Krapf, C.

AU - Amberger, A.

AU - Brandacher, G.

AU - Landin, L.

AU - Müller, H.

AU - Schön, M. P.

AU - Cavadas, P.

AU - Lee, A. W.P.

AU - Pratschke, J.

AU - Margreiter, R.

AU - Schneeberger, S.

N1 - Funding Information: This work was done as part of the cooperation program between the Serbian Academy of Sciences and Arts and the Institute for the Problems of Material Science of the National Academy of Sciences of the Ukraine, i.e. as part of the project ‘Synthesis of functional materials in accordance with the synthesis-structure-properties-application relationship’ financed by the Ministry for Science and Technology of Serbia, and partially through NEDO International Joint Research Grant Program: “Wetability of solid by liquid at high temperatures”.

PY - 2010/5

Y1 - 2010/5

N2 - Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

AB - Skin rejection remains a major hurdle in reconstructive transplantation. We investigated molecular markers of skin rejection with particular attention to lymphocyte trafficking. Skin biopsies (n = 174) from five human hand transplant recipients were analyzed for rejection, characteristics of the infiltrate and lymphocytic adhesion markers. The cellular infiltrate predominantly comprised CD3+ T cells. CD68, Foxp3 and indoleamine 2, 3-dioxygenase expression and the CD4/CD8 increased with severity of rejection. Lymphocyte adhesion markers were upregulated upon rejection, intercellular adhesion molecule-1 and E-selectin correlated best with severity of rejection. Guided by the findings, a specific E- and P-selectin inhibitor was investigated for its effect on skin rejection in a rat hind limb allotransplant model. While efomycine M (weekly s.c. injection into the graft) alone had no effect, long-term allograft survival was achieved when combined with antithymocyte globulin and tacrolimus (control group without efomycine M rejected at postoperative day [POD] 61 ± 1). Upregulation of lymphocyte trafficking markers correlates with severity of skin rejection and time after transplantation in human hand transplantation. Blocking E- and P-selectin in the skin holds potential to significantly prolong limb allograft survival.

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KW - Composite tissue allograft

KW - Composite tissue transplantation

KW - Hand transplantation

KW - Lymphocyte trafficking

KW - Rat

KW - Rejection

KW - Selectin ligand inhibition

KW - Skin

KW - Topical therapy

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SN - 1600-6135

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EP - 1209

JO - American Journal of Transplantation

JF - American Journal of Transplantation

IS - 5

ER -

Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation

Abstract

Keywords

ASJC Scopus subject areas

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