Open AccessLymphoid neogenesis in skin of human hand, nonhuman primate, and rat vascularized composite allografts
Author(s) -
Hautz Theresa,
Zelger Bettina G.,
Nasr Isam W.,
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
Publication year - 2014
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/tri.12358
Subject(s) - neogenesis , transplantation , nonhuman primate , addressin , human skin , lymphatic system , infiltration (hvac) , pathology , immunohistochemistry , medicine , cell adhesion molecule , biology , immunology , cell adhesion , cell , genetics , physics , islet , evolutionary biology , insulin , thermodynamics
Summary 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) VCA s 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 ( PNA d) was performed and correlated with rejection and time post‐transplantation. TLO were identified in human, nonhuman primate, and rat skin samples. Expression of PNA d 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. PNA d expression was observed at all time‐points after transplantation and increased significantly after year 5. In nonhuman primate skin, PNA d expression was found during inflammatory conditions early and late after transplantation. In rat skin, PNA d 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 . PNA d expression in vascular endothelium correlates with skin rejection and T‐ and B‐cell infiltration.