Histopathologic characterization of mild rejection (grade I) in skin biopsies of human hand allografts

Mild skin rejection is a common observation in reconstructive transplantation. To enlighten the role of this inflammatory reaction we investigated markers for cellular and antibody mediated rejection, adhesion molecules and tolerance markers. Forty‐seven skin biopsies (rejection grade I) of human hand allografts were investigated by immunohistochemistry (CD3, CD4, CD8, CD20, CD68, C4d, LFA‐1, ICAM‐1, E‐selectin, P‐selectin, VE‐cadherin, HLA‐DR, IDO, and Foxp3). Expression was read with respect to time after transplant. The infiltrate was mainly comprised of CD3+T‐lymphocytes. Among these, CD8+cells were more prominent than CD4+cells. CD20+B‐lymphocytes were sparse and CD68+macrophages were found in some, but not all samples (approximately 10% of the infiltrate). The CD4/CD8‐ratio was increased after the first year. C4d staining was mainly positive in samples at time‐points later than 1 year. Adhesion molecules LFA‐1, ICAM‐1, E‐selectin, P‐selectin, and VE‐cadherin were found upregulated, and for P‐selectin, expression increased with time after transplant. IDO expression was strongest at 3 months–1 year post‐transplant and a tendency toward more Foxp3+ cells at later time points was observed. Mild skin rejection after hand transplantation presents with a T‐cell dominated dermal cell infiltrate and upregulation of adhesion molecules. The role of C4d expression after year one remains to be elucidated.