Document Detail


Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.
MedLine Citation:
PMID:  21557779     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Small bowel transplantation (SBT) is becoming a preferred treatment for patients with irreversible intestinal failure. Despite continuous improvement of immunosuppression, SBT is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need for reliable detection markers and novel immunosuppressive strategies that can achieve better control of ACR. We hypothesized that particular transcriptomes provide critical regulation of the intragraft immune response. The aim of our study was to detect potential molecular biomarkers for identifying ACR in minute mucosal biopsies. We examined 30 intestinal mucosal biopsies (AR/NR; 17/13) obtained from recipients after SBT or multivisceral transplantation. We utilized TaqMan® Gene Signature Arrays (immune, inflammation and apoptosis) and investigated the expression of 280 genes. As one of our validations, we performed immunohistochemistry for selected targets. We detected 252 mRNAs in total, 92 of which were found with significantly different expression levels between the AR and NR groups. Immunohistochemistry showed significantly increased staining for IL1R2, ICAM1, GZMB, and CCL3 (P < 0.05) during ACR. For the first time, we characterize the potential molecular changes that are associated with modulation of histological appearances of intestinal ACR. These differences in transcriptome patterns can be used to identify robust biomarkers and potential novel therapeutic targets for immunosuppressive agents.
Authors:
Tadafumi Asaoka; Eddie R Island; Panagiotis Tryphonopoulos; Gennaro Selvaggi; Jang Moon; Akin Tekin; Alexandra Amador; David M Levi; Jennifer Garcia; Leslie Smith; Seigo Nishida; Debbie Weppler; Andreas G Tzakis; Phillip Ruiz
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-5-9
Journal Detail:
Title:  Transplant international : official journal of the European Society for Organ Transplantation     Volume:  -     ISSN:  1432-2277     ISO Abbreviation:  -     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-5-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8908516     Medline TA:  Transpl Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2011 The Authors. Transplant International © 2011 European Society for Organ Transplantation.
Affiliation:
 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA  Department of Pediatrics, University of Miami Miller School of Medicine, Miami, FL, USA.
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