Open AccessTribbles-1 as a Novel Biomarker of Chronic Antibody-Mediated Rejection
Author(s) -
Joanna AshtonChess,
Magali Giral,
Michael Mengel,
Karine Renaudin,
Yohann Foucher,
Wilfried Gwinner,
Christophe Braud,
Emilie Dugast,
Thibaut Quillard,
Paméla Thébault,
Elise Chiffoleau,
Cécile Braudeau,
Béatrice Charreau,
JeanPaul Soulillou,
Sophie Brouard
Publication year - 2008
Publication title -
journal of the american society of nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.451
H-Index - 279
eISSN - 1533-3450
pISSN - 1046-6673
DOI - 10.1681/asn.2007101056
Subject(s) - biomarker , medicine , peripheral blood mononuclear cell , antibody , microarray , immune system , immunology , downregulation and upregulation , pathology , gene , gene expression , biology , biochemistry , in vitro
Diagnosis of the specific cause of late allograft injury is necessary if more personalized and efficient immunosuppressive regimens are to be introduced. This study sought previously unrecognized biomarkers for specific histologic diagnoses of late graft scarring by comparison of gene sets from published microarray studies. Tribbles-1 (TRIB1), a human homolog of Drosophila tribbles, was identified to be a potentially informative biomarker. For testing this, mRNA expression in 76 graft biopsies, 71 blood samples, and 11 urine samples were profiled from independent cohorts of renal transplant patients with different histologic diagnoses recruited at two European centers. TRIB1 but not TRIB2 or TRIB3 was found to be a potential blood and tissue biomarker of chronic antibody-mediated rejection, an active immune-mediated form of chronic allograft failure associated with a poor prognosis. TRIB1 mRNA levels in peripheral blood mononuclear cells discriminated patients with chronic antibody-mediated rejection from those with other types of late allograft injury with high sensitivity and specificity. TRIB1 was also upregulated in a rodent model of chronic cardiac vasculopathy, suggesting that this biomarker may be useful in other solid-organ transplants and across species. It was determined that TRIB1 is expressed primarily by antigen-presenting cells and activated endothelial cells. Overall, these data support the potential use of TRIB1 as a biomarker of chronic antibody-mediated allograft failure.