Document Detail


Value of FOXP3 expression in peripheral blood as rejection marker after miniature swine lung transplantation.
MedLine Citation:
PMID:  19059109     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. 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. 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]). 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.
Authors:
Naoki Satoda; Tsuyoshi Shoji; Yanling Wu; Takuji Fujinaga; Fengshi Chen; Akihiro Aoyama; Ji Tian Zhang; Ayuko Takahashi; Toshihiro Okamoto; Izumi Matsumoto; Hiroaki Sakai; Ying Li; Xiangdong Zhao; Toshiaki Manabe; Eiji Kobayashi; Shimon Sakaguchi; Hiromi Wada; Hidenori Ohe; Shinji Uemoto; Junichi Tottori; Toru Bando; Hiroshi Date; Takaaki Koshiba
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  27     ISSN:  1557-3117     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-08     Completed Date:  2009-06-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1293-301     Citation Subset:  IM    
Affiliation:
Department of Thoracic Surgery, Kyoto University, Kyoto, Japan.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
DNA Primers
Fas Ligand Protein / blood,  genetics
Female
Forkhead Transcription Factors / blood*,  genetics*
Graft Rejection / blood*,  diagnosis
Immunosuppressive Agents / therapeutic use
Lung Transplantation / adverse effects*,  immunology
Male
Perforin / blood,  genetics
RNA, Messenger / blood,  genetics*
Reperfusion / methods
Swine
Swine, Miniature
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Fas Ligand Protein; 0/Forkhead Transcription Factors; 0/Immunosuppressive Agents; 0/RNA, Messenger; 126465-35-8/Perforin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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