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

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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1200-1209
Number of pages10
JournalAmerican Journal of Transplantation
Volume10
Issue number5
DOIs
StatePublished - May 2010
Externally publishedYes

Fingerprint

Vascularized Composite Allotransplantation
Molecular Targeted Therapy
Skin
E-Selectin
P-Selectin
Lymphocytes
Allografts
Hand Transplantation
Extremities
Transplantation
Indoleamine-Pyrrole 2,3,-Dioxygenase
Antilymphocyte Serum
Tacrolimus
Intercellular Adhesion Molecule-1
Up-Regulation
Hand
T-Lymphocytes
Transplants
Biopsy
Control Groups

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

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation. / Hautz, T.; Zelger, B.; Grahammer, J.; Krapf, C.; Amberger, A.; Brandacher, Gerald; Landin, L.; Müller, H.; Schön, M. P.; Cavadas, P.; Lee, W P Andrew; Pratschke, J.; Margreiter, R.; Schneeberger, S.

In: American Journal of Transplantation, Vol. 10, No. 5, 05.2010, p. 1200-1209.

Research output: Contribution to journalArticle

Hautz, T, Zelger, B, Grahammer, J, Krapf, C, Amberger, A, Brandacher, G, Landin, L, Müller, H, Schön, MP, Cavadas, P, Lee, WPA, 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
Hautz, T. ; Zelger, B. ; Grahammer, J. ; Krapf, C. ; Amberger, A. ; Brandacher, Gerald ; Landin, L. ; Müller, H. ; Schön, M. P. ; Cavadas, P. ; Lee, W P Andrew ; Pratschke, J. ; Margreiter, R. ; Schneeberger, S. / Molecular markers and targeted therapy of skin rejection in composite tissue allotransplantation. In: American Journal of Transplantation. 2010 ; Vol. 10, No. 5. pp. 1200-1209.
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