Tribbles-1 as a novel biomarker of chronic antibody-mediated rejection.
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.
Ashton-Chess
Joanna
J
INSERM U643, Centre Hospitalier Universitaire Nantes, Institut de Transplantation et de Recherche en Transplantation, Nantes, France.
Giral
Magali
M
Mengel
Michael
M
Renaudin
Karine
K
Foucher
Yohann
Y
Gwinner
Wilfried
W
Braud
Christophe
C
Dugast
Emilie
E
Quillard
Thibaut
T
Thebault
Pamela
P
Chiffoleau
Elise
E
Braudeau
Cécile
C
Charreau
Béatrice
B
Soulillou
Jean-Paul
JP
Brouard
Sophie
S
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis* / Q000235:genetics; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000032:analysis* / Q000235:genetics / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000032:analysis
D015415:Biomarkers; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C493170:TRIB1 protein, human; D017346:Protein Serine-Threonine Kinases