Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts

Theresa Hautz, Bettina G. Zelger, Isam Nasr, Gerhard S. Mundinger, Rolf N. Barth, Eduardo D. Rodriguez, Gerald Brandacher, Annemarie Weissenbacher, Bernhard Zelger, Pedro Cavadas, Raimund Margreiter, W P Andrew Lee, Johann Pratschke, Fadi G. Lakkis, Stefan Schneeberger

Research output: Contribution to journalArticle

Abstract

The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.

Original languageEnglish (US)
Pages (from-to)966-976
Number of pages11
JournalTransplant International
Volume27
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Composite Tissue Allografts
Primates
Hand
Vascularized Composite Allotransplantation
Skin
Transplantation
Hand Transplantation
Lymphocyte Function-Associated Antigen-1
Vascular Endothelium
Lymphocyte Count
Endothelium
B-Lymphocytes
Staining and Labeling
T-Lymphocytes
Biopsy

Keywords

  • allograft rejection
  • lymphoid neogenesis
  • peripheral node addressin
  • tertiary lymphoid organs
  • vascularized composite allotransplantation

ASJC Scopus subject areas

  • Transplantation
  • Medicine(all)

Cite this

Hautz, T., Zelger, B. G., Nasr, I., Mundinger, G. S., Barth, R. N., Rodriguez, E. D., ... Schneeberger, S. (2014). Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts. Transplant International, 27(9), 966-976. https://doi.org/10.1111/tri.12358

Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts. / Hautz, Theresa; Zelger, Bettina G.; Nasr, Isam; Mundinger, Gerhard S.; Barth, Rolf N.; Rodriguez, Eduardo D.; Brandacher, Gerald; Weissenbacher, Annemarie; Zelger, Bernhard; Cavadas, Pedro; Margreiter, Raimund; Lee, W P Andrew; Pratschke, Johann; Lakkis, Fadi G.; Schneeberger, Stefan.

In: Transplant International, Vol. 27, No. 9, 2014, p. 966-976.

Research output: Contribution to journalArticle

Hautz, T, Zelger, BG, Nasr, I, Mundinger, GS, Barth, RN, Rodriguez, ED, Brandacher, G, Weissenbacher, A, Zelger, B, Cavadas, P, Margreiter, R, Lee, WPA, Pratschke, J, Lakkis, FG & Schneeberger, S 2014, 'Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts', Transplant International, vol. 27, no. 9, pp. 966-976. https://doi.org/10.1111/tri.12358
Hautz, Theresa ; Zelger, Bettina G. ; Nasr, Isam ; Mundinger, Gerhard S. ; Barth, Rolf N. ; Rodriguez, Eduardo D. ; Brandacher, Gerald ; Weissenbacher, Annemarie ; Zelger, Bernhard ; Cavadas, Pedro ; Margreiter, Raimund ; Lee, W P Andrew ; Pratschke, Johann ; Lakkis, Fadi G. ; Schneeberger, Stefan. / Lymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts. In: Transplant International. 2014 ; Vol. 27, No. 9. pp. 966-976.
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abstract = "The mechanisms of skin rejection in vascularized composite allotransplantation (VCA) remain incompletely understood. The formation of tertiary lymphoid organs (TLO) in hand transplantation has been recently described. We assess this phenomenon in experimental and clinical VCA rejection. Skin biopsies of human (n = 187), nonhuman primate (n = 11), and rat (n = 15) VCAs were analyzed for presence of TLO. A comprehensive immunohistochemical assessment (characterization of the cell infiltrate, expression of adhesion molecules) including staining for peripheral node addressin (PNAd) was performed and correlated with rejection and time post-transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNAd was increased in the endothelium of vessels upon rejection in human skin (P = 0.003) and correlated with B- and T-lymphocyte numbers and LFA-1 expression. PNAd expression was observed at all time-points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNAd expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNAd expression was strongly associated with acute rejection and time post-transplantation. Lymphoid neogenesis and TLO formation can be uniformly found in experimental and human VCA. PNAd expression in vascular endothelium correlates with skin rejection and T- and B-cell infiltration.",
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