Intragraft immunological events associated with EBV DNAemia in liver transplant patients

Epstein-Barr virus (EBV) may cause post-transplant lymphoproliferative disorder, but most EBV infections after liver transplantation (Ltx) are clinically silent reactivations. In this study, we investigated the intragraft immunological events associated with EBV DNAemia. Altogether, 105 adult Ltx patients were monitored for EBV DNAemia. Fourteen (13%) patients developed EBV DNAemia during the first year after transplantation. Liver biopsies obtained associated with EBV DNAemia, without evidence of other herpes or hepatitis viruses or rejection, were available from five patients. The numbers of lymphocytes positive for B-cell marker (CD20), T-cell markers (CD3, CD4 and CD8) and IL-2R, adhesion molecules (ICAM-1, VCAM-1 and ELAM-1) and their ligands [lymphocyte function-associated antigen-1 (LFA-1), very late antigen (VLA-4) and Sialyl Lewis X (sLeX)] were demonstrated in liver biopsies by immunohistochemistry, and zero-biopsies from donor livers were used as controls. EBV DNAemia was associated with increased number of CD20-positive (22±30, p=0.09) and significantly increased numbers of CD3 (80±16, p=0.001)-, CD4 (23±8, p=0.009)- and CD8 (38±8, p=0.001)-positive lymphocytes in the graft. ICAM-1, but not VCAM-1 or ELAM-1, was strongly expressed and the number of LFA-1-positive cells was significantly increased (48±10, p=0.0002). Low-level EBV DNAemia was associated with B- and especially T-cell infiltration of the graft, as well as an increase in ICAM-1 and the number of LFA-1-positive cells. However, EBV DNAemia or these immunological events did not have any effect on the liver transplant.