Blockade of intragraft IL-2 receptor-alpha by basiliximab is insufficient to prevent activation of liver graft infiltrating cells.
Treatment with basiliximab, a CD25 (Interleukin-2 receptor-alpha; IL-2Ralpha)-blocking human-murine chimeric antibody, reduces the incidence of acute rejections after organ transplantation, but rejection is not completely prevented. We investigated whether rejections during basiliximab treatment were due to insufficient exposure to the antibody or to incomplete blockade of intragraft CD25, and whether CD25-blockade affected activation of liver transplant infiltrating cells. Twenty-seven basiliximab-treated liver transplant recipients and seven patients not treated with basiliximab, from which post-transplant liver biopsies were available, were retrospectively selected for this study. Rejectors among the basiliximab-treated patients (n=11) had not cleared basiliximab from their blood at a faster rate than non-rejectors (n=16). Rejections within the period of saturating serum basiliximab concentrations were in most cases not due to insufficient intragraft CD25-blockade: in eight out of eleven rejection biopsies obtained during this period CD25 on graft-infiltrating cells was completely coated by basiliximab. Despite CD25 blockade, portal infiltrates in these biopsies showed similar expression of the proliferation-associated antigen Ki-67 and of the cytotoxic effector molecules granzyme A and B as those in rejection biopsies obtained from patients not treated with basiliximab. In conclusion, basiliximab treatment of liver transplant patients results in blockade of intragraft CD25, but nevertheless cells in rejection infiltrates are strongly activated, probably by a mechanism bypassing the IL-2Ralpha.
Kwekkeboom
Jaap
J
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. kwekkeboom@mdk.azr.nl
Warlé
Michiel C
MC
Rietveld
John
J
Segeren
Katja C A
KC
Tilanus
Hugo W
HW
Metselaar
Herold J
HJ
D000911:Antibodies, Monoclonal / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077552:Basiliximab; D002455:Cell Division / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors*; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases / Q000378:metabolism
D000911:Antibodies, Monoclonal; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D018123:Receptors, Interleukin; D011993:Recombinant Fusion Proteins; D000077552:Basiliximab; D012697:Serine Endopeptidases