Posttransplant lymphoproliferative disorder after liver transplantation in miniature swine.
BACKGROUND
Posttransplant lymphoproliferative disorder (PTLD) is a well-known, life-threatening complication of immunosuppressive therapy, occurring in both adult and pediatric transplant recipients.


METHODS
To study the effect of major histocompatibility complex on tolerance induction to primarily vascularized liver allograft, a semi-identical miniature swine model was developed to mimic the clinical situation of parent-into-infant liver transplantation. Long-term acceptance of semi-identical liver allograft was obtained by a transient course of FK506. In a subgroup of six animals, three developed a lethal PTLD. These animals were studied by histology and immunohistochemistry and the anti-donor cellular immune response was assessed. In addition, the possible viral origin of the proliferative process was evoked.


RESULTS
Histology and immunohistochemistry revealed an abnormal B-cell proliferation in many organs of swine suffering from PTLD. Evidence of human Epstein-Barr virus, cytomegalovirus, and adenovirus was not evidenced, but a porcine virus responsible for a respiratory and reproductive syndrome (PRRS) was identified in the lymphoid tissue of these animals. In mixed lymphocyte reaction, a significant antiself immune response confirmed an infection by a virus.


CONCLUSIONS
This is the first report suggesting that PRRS virus might provoke PTLD in immunosuppressed miniature swine after orthotopic liver transplantation. Whether PTLD could be induced by injection of the PRRS virus in immunosuppressed animals, a pig model of PTLD might be developed and would represent an interesting preclinical model for testing anti-PTLD therapies.
Talpe
S
S
Laboratory of Experimental Surgery, University of Louvain Medical School, CHEX/5570, Avenue Hippocrate 55, B-1200 Brussels, Belgium.
Oike
F
F
Dehoux
J P
JP
Sempoux
C
C
Rahier
J
J
Otte
J B
JB
Gianello
P
P
D000818:Animals; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D016031:Liver Transplantation / Q000009:adverse effects; D007959:Lymphocyte Culture Test, Mixed; D008221:Lymphoid Tissue / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000821:virology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000175:diagnosis / Q000821:virology; D019316:Porcine respiratory and reproductive syndrome virus / Q000302:isolation & purification; D013552:Swine; D013556:Swine, Miniature