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Posttransplant Lymphoproliferative Disorders in Neuronal Xenotransplanted Macaques
L Cavicchioli1, S Ferraresso1, S Westmoreland2
11 Department of Comparative Biomedicine and Food Science, Padova University, Padova, Italy.
Veterinary Pathology
|October 4, 2016
Summary
Posttransplant lymphoproliferative disorders (PTLDs) in immunosuppressed primates were linked to macaca lymphocryptovirus. Monitoring this virus may enable early PTLD diagnosis and treatment by reducing immunosuppression.
Area of Science:
- Transplantation immunology
- Virology
- Oncology
Background:
- Posttransplant lymphoproliferative disorders (PTLDs) arise from T-cell dysfunction post-transplantation.
- Immunosuppression is critical but increases PTLD risk.
- Xenotransplantation presents unique challenges for immune tolerance and disease monitoring.
Purpose of the Study:
- To investigate PTLD development in immunosuppressed primates receiving porcine xenografts.
- To identify the viral association and potential diagnostic markers for PTLD.
- To assess zoonotic transmission risk of porcine viruses.
Main Methods:
- Intracerebral injection of wild-type or CTLA4-Ig transgenic porcine xenografts into 28 immunosuppressed parkinsonian macaques.
- Histopathological classification of developed masses using WHO criteria.
- Immunohistochemistry, PCR, and quantitative PCR to detect macaca lymphocryptovirus (MLCV) and viral load.
Main Results:
- 32% of primates developed monomorphic PTLD, primarily in the gastrointestinal tract and/or nasal cavity.
- PTLDs were strongly associated with MLCV, with viral protein found in neoplastic B cells.
- Viral load progression correlated with PTLD progression, with no evidence of porcine virus zoonosis.
Conclusions:
- MLCV is implicated in PTLD development in this xenotransplantation model.
- Monitoring MLCV DNA levels could serve as an early diagnostic tool for PTLD progression.
- This monitoring may allow for timely therapeutic interventions, such as reducing immunosuppression.
