title: Characteristic immune, apoptosis and inflammatory gene profiles associated with intestinal acute cellular rejection in formalin-fixed paraffin-embedded mucosal biopsies.
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.
authors.affiliation: Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Asaoka
authors.forename: Eddie R
authors.initials: ER
authors.lastname: Island
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Tryphonopoulos
authors.forename: Gennaro
authors.initials: G
authors.lastname: Selvaggi
authors.forename: Jang
authors.initials: J
authors.lastname: Moon
authors.forename: Akin
authors.initials: A
authors.lastname: Tekin
authors.forename: Alexandra
authors.initials: A
authors.lastname: Amador
authors.forename: David M
authors.initials: DM
authors.lastname: Levi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garcia
authors.forename: Leslie
authors.initials: L
authors.lastname: Smith
authors.forename: Seigo
authors.initials: S
authors.lastname: Nishida
authors.forename: Debbie
authors.initials: D
authors.lastname: Weppler
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakis
authors.forename: Phillip
authors.initials: P
authors.lastname: Ruiz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D054405:Chemokine CCL3 / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005404:Fixatives; D005557:Formaldehyde; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D007150:Immunohistochemistry; D007223:Infant; D007413:Intestinal Mucosa / Q000473:pathology / Q000503:physiopathology; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D008875:Middle Aged; D016612:Paraffin Embedding; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: C403514:CADM1 protein, human; C515429:CCL3 protein, human; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D054405:Chemokine CCL3; D005404:Fixatives; D007136:Immunoglobulins; D005557:Formaldehyde