Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 697-707 |
| Number of pages | 11 |
| Journal | Transplant International |
| Volume | 24 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2011 |
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Keywords
- Gene signature
- Human
- Molecular biomarker
- Multivisceral transplantation
- Small bowel transplantation
ASJC Scopus subject areas
- Transplantation
Cite this
Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies. / Asaoka, Tadafumi; Island, Eddie R.; Tryphonopoulos, Panagiotis; Selvaggi, Gennaro; Moon, Jang; Tekin, Akin; Amador, Alexandra; Levi, David M.; Garcia, Jennifer; Smith, Lesley J; Nishida, Seigo; Weppler, Debbie; Tzakis, Andreas G.; Ruiz, Phillip.
In: Transplant International, Vol. 24, No. 7, 01.07.2011, p. 697-707.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies
AU - Asaoka, Tadafumi
AU - Island, Eddie R.
AU - Tryphonopoulos, Panagiotis
AU - Selvaggi, Gennaro
AU - Moon, Jang
AU - Tekin, Akin
AU - Amador, Alexandra
AU - Levi, David M.
AU - Garcia, Jennifer
AU - Smith, Lesley J
AU - Nishida, Seigo
AU - Weppler, Debbie
AU - Tzakis, Andreas G.
AU - Ruiz, Phillip
PY - 2011/7/1
Y1 - 2011/7/1
N2 - 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.
AB - 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.
KW - Gene signature
KW - Human
KW - Molecular biomarker
KW - Multivisceral transplantation
KW - Small bowel transplantation
UR - http://www.scopus.com/inward/record.url?scp=79959846503&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959846503&partnerID=8YFLogxK
U2 - 10.1111/j.1432-2277.2011.01259.x
DO - 10.1111/j.1432-2277.2011.01259.x
M3 - Article
VL - 24
SP - 697
EP - 707
JO - Transplant International
JF - Transplant International
SN - 0934-0874
IS - 7
ER -