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

作者：Hautz T; Zelger B; Grahammer J; Krapf C; Amberger A; Brandacher G; Landin L; Mueller H; Schoen M P; Cavadas P; Lee A W P; Pratschke J; Margreiter R; Schneeberger S^*

来源：American Journal of Transplantation, 2010, 10(5): 1200-1209.

DOI：10.1111/j.1600-6143.2010.03075.x

• Adhesion molecules
• composite tissue allograft
• composite tissue transplantation
• hand transplantation
• lymphocyte trafficking
• rat
• rejection
• selectin ligand inhibition
• skin
• topical therapy

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.

• 出版日期2010-5