Evaluation of parathyroid hormone as a functional biological marker of rat laryngeal transplant rejection.
OBJECTIVE
Short-term immunosuppressive protocols in a preclinical rat model that have led to prolonged survival of the graft in preliminary trials were investigated. Rat allografts, by their heterotopic nature, do not allow direct examination or functional interpretation. The primary objective of the study was to identify a reliable functional biological marker allowing monitoring of graft status. A secondary goal was to use this marker to indicate onset of rejection.


METHODS
The authors elected to study rat parathyroid hormone as a functional marker of laryngotracheal complex rejection. Theoretically, a pulsed immunosuppressive regimen that is administered when parathyroid hormone levels begin to fall could prevent rejection.


METHODS
Eleven Lewis recipient rats underwent parathyroidectomy one week before laryngeal transplantation. Parathyroid hormone levels were obtained on various days following transplantation, then analyzed with an intact rat parathyroid hormone assay. Animals were killed on different days to allow for comparison of parathyroid hormone levels with histopathological signs of rejection.


RESULTS
All animals had undetectable levels of parathyroid hormone before transplantation. By 24 hours after transplantation, parathyroid hormone levels were within normal range. At 72 hours, the parathyroid hormone levels dropped precipitously. Rejection of parathyroid glands paralleled the early histological changes of rejection seen in the other anatomical areas of interest in the laryngotracheal graft.


CONCLUSIONS
The study represents the first time a hematological marker has been identified that has predictive value for rejection of transplanted rat larynges. As such, it not only enables a 3-month experimental window with reasonable numbers of animals, but also opens the door for novel sequencing of immunosuppressive modalities.
Nelson
Marc
M
Department of Otolaryngology and Communicative Disorders, The Cleveland Clinic Foundation, Ohio 44195, USA. nelsonm1@ccf.org
Dan
Olivia
O
Strome
Marshall
M
D000818:Animals; D015415:Biomarkers / Q000097:blood*; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007830:Larynx / Q000473:pathology / Q000637:transplantation*; D010280:Parathyroid Glands / Q000473:pathology / Q000637:transplantation; D010281:Parathyroid Hormone / Q000097:blood*; D016105:Parathyroidectomy; D011237:Predictive Value of Tests; D020551:Pulse Therapy, Drug; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous
D015415:Biomarkers; D007166:Immunosuppressive Agents; D010281:Parathyroid Hormone