Analysis of Acute and Chronic Rejection in Multiple Organ Allografts From Retransplantation and Autopsy Cases of Multivisceral Transplantation

Takahashi, Hitomi; Kato, Tomoaki; Delacruz, Victor; Nishida, Seigo; Selvaggi, Gennaro; Weppler, D.; Island, Eddie; Moon, Jang; Levi, David; Tzakis, Andreas G.; Ruiz, Phillip

doi:10.1097/tp.0b013e318174d857

Cited by 19 publications

(11 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multivisceral transplantation (MVT) is one of the forms of SBT. Previous reports have suggested that the small intestinal allograft (particularly the ileum) is the most susceptible organ to acute cellular rejection (ACR) in frequency and severity when compared with other allografts within the MVT and it has been recognized as the Achilles heel and critical organ of MVT [4]. Therefore, in the management of intestinal graft, the early detection and treatment of ACR is essential.…”

Section: Introductionmentioning

confidence: 99%

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies

Asaoka

Island

Tryphonopoulos

et al. 2011

Transplant International

Self Cite

View full text Add to dashboard Cite

Summary 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.

show abstract

Section: Introductionmentioning

confidence: 99%

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies

Asaoka

Island

Tryphonopoulos

et al. 2011

Transplant International

Self Cite

View full text Add to dashboard Cite

show abstract

“…Multivisceral transplantation (MVT) is one of the forms of SBT. Previous reports have suggested that the small intestinal allograft (particularly the ileum) is the most susceptible organ to ACR in frequency and severity when compared with other allografts within the MVT and it has been recognized as the "Achilles heel" and critical organ of MVT (4). Therefore, accurate diagnosis and treatment of ACR are critical for posttransplant patient care.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA Signature of Intestinal Acute Cellular Rejection in Formalin-Fixed Paraffin-Embedded Mucosal Biopsies

Asaoka

Sotolongo

Island

et al. 2012

American Journal of Transplantation

View full text Add to dashboard Cite

Despite continuous improvement of immunosuppression, small bowel transplantation (SBT) is plagued by a high incidence of acute cellular rejection (ACR) that is frequently intractable. Therefore, there is a need to uncover novel insights that will lead to strategies to achieve better control of ACR. We hypothesized that particular miRNAs provide critical regulation of the intragraft immune response. The aim of our study was to identify miRNAs involved in intestinal ACR. We examined 26 small intestinal mucosal biopsies (AR/NR group; 15/11) obtained from recipients after SBT or multivisceral transplantation. We investigated the expression of 384 mature human miRNAs and 280 mRNAs associated with immune, inflammation and apoptosis processes. We identified differentially expressed 28 miRNAs and 58 mRNAs that characterized intestinal ACR. We found a strong positive correlation between the intragraft expression levels of three miRNAs (miR-142-3p, miR-886-3p and miR-132) and 17 mRNAs including CTLA4 and GZMB. We visualized these miRNAs within cells expressing CD3 and CD14 proteins in explanted intestinal allografts with severe ACR. Our data suggested that miRNAs have a critical role in the activation of infiltrating cells during intestinal ACR. These differences in miRNA expression patterns can be used to identify novel biomarkers and therapeutic targets for immunosuppressive agents.

show abstract

“…Encapsulating peritoneal sclerosis has also been described in a few cases, although this finding is usually evident only in the operating room [38]. Most studies of chronic rejection have focused on the histology of explants after death or graft enterectomy [17,37]. This is due to the fact that intestinal mucosal biopsies are too superficial to evaluate the small and medium-sized vessels located in the muscularis mucosae layer of the intestinal wall.…”

Section: Chronic Rejectionmentioning

confidence: 95%

“…In a paper describing the relative frequency of rejection in multivisceral transplant organ explant specimens, overall detection of ACR in the small intestine was in 25.5% of cases, 12.2% in the stomach, and 16% in the large intestine. In patients undergoing ACR, the relative frequencies were 80.0% in the small intestine, 38.5% in the stomach, and 33.3% in the large intestine [17]. If the distal ileum cannot be reached, the proximal jejunum can be sampled as an alternate site.…”

Section: Diagnosismentioning

confidence: 99%

Clinical Allograft Rejection Syndromes in Intestinal Transplantation

Tzakis

Selvaggi

Tekin

et al. 2014

Textbook of Organ Transplantation

Self Cite

View full text Add to dashboard Cite

Analysis of Acute and Chronic Rejection in Multiple Organ Allografts From Retransplantation and Autopsy Cases of Multivisceral Transplantation

Abstract: Our study clearly indicated variation in organ susceptibility to ACR and CR. Small intestinal allografts were the most susceptible organ to ACR in frequency and severity. Pancreatic allografts may be more susceptible to CR in comparison with ACR.

Cited by 19 publications

References 30 publications

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies

Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies

MicroRNA Signature of Intestinal Acute Cellular Rejection in Formalin-Fixed Paraffin-Embedded Mucosal Biopsies

Clinical Allograft Rejection Syndromes in Intestinal Transplantation

Contact Info

Product

Resources

About