Details

Autor(en) / Beteiligte

• 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.

Titel

Molecular Markers and Targeted Therapy of Skin Rejection in Composite Tissue Allotransplantation

Ist Teil von

• American journal of transplantation, 2010-05, Vol.10 (5), p.1200-1209

Ort / Verlag

Malden, USA: Blackwell Publishing Inc

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Upregulation of lymphocyte adhesion molecules found in human hand transplant skin biopsies correlates with severity of skin rejection and time after transplantation and local inhibition of E‐ and P‐selectin in the skin holds potential to significantly prolong limb allograft survival.