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Value of FOXP3 expression in peripheral blood as rejection marker after miniature swine lung transplantation.
- Source :
-
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2008 Dec; Vol. 27 (12), pp. 1293-301. - Publication Year :
- 2008
-
Abstract
- Background: Outcome for highly immunogenic lung transplantation remains unsatisfactory despite the development of potent immunosuppressants. The poor outcome may be the result of a lack of minimally invasive methods to detect early rejection. There is emerging clinical evidence that, paradoxically, expression of forkhead box P3 (FOXP3, a specific marker for the regulatory T cells) is upregulated within rejecting grafts.<br />Methods: Orthotopic lung transplantation was performed using miniature swine without immunosuppression. Rejection was monitored by chest radiography and open lung biopsy. Expressions levels of FOXP3, perforin, Fas-L and IP-10 mRNA were quantified in the peripheral blood. In addition, rescue immunosuppressive therapy (steroid plus tacrolimus) was administered on post-operative day (POD) 4 or 6.<br />Results: Early rejection was detected by open lung biopsy, but misdiagnosed by chest radiography on POD 4. Expression of FOXP3 in the peripheral blood reached its highest value as early as POD 4, followed by a decline. Such an increase of FOXP3 was not observed in recipients given high-dose tacrolimus. Neither perforin, Fas-L or IP-10 in the peripheral blood exhibited significant fluctuations in the early phase of rejection. Rescue immunosuppressive therapy from POD 4, when peak FOXP3 was seen, prolonged graft survival (27.2 days, versus 9.1 days without immunosuppression, p < 0.001), in contrast to POD 6, when rejection was suspected by chest radiography (11.5 days, p = not statistically significant [NS]).<br />Conclusions: In a miniature swine lung transplantation model, the FOXP3 mRNA level in the peripheral blood was upregulated at an early phase of rejection. The clinical implication of this finding remains to be elucidated.
- Subjects :
- Acute Disease
Animals
DNA Primers
Fas Ligand Protein blood
Fas Ligand Protein genetics
Female
Graft Rejection diagnosis
Immunosuppressive Agents therapeutic use
Lung Transplantation immunology
Male
Perforin blood
Perforin genetics
RNA, Messenger blood
Reperfusion methods
Swine
Swine, Miniature
Forkhead Transcription Factors blood
Forkhead Transcription Factors genetics
Graft Rejection blood
Lung Transplantation adverse effects
RNA, Messenger genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1557-3117
- Volume :
- 27
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 19059109
- Full Text :
- https://doi.org/10.1016/j.healun.2008.08.006