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Discovery and cross-validation of peripheral blood and renal biopsy gene expression signatures from ethnically diverse kidney transplant populations.
Ventura, Carlucci G; Whisenant, Thomas; Gelbart, Terri; David, Daisa S R; Agena, Fabiana; Salomon, Daniel R; David-Neto, Elias; Kurian, Sunil M.
Affiliation
  • Ventura CG; Renal Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
  • Whisenant T; University of California, San Diego, School of Medicine, Center for Computational Biology and Bioinformatics, La Jolla, California.
  • Gelbart T; Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California.
  • David DSR; Renal Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
  • Agena F; Renal Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
  • David-Neto E; Renal Transplant Service, Hospital das Clinicas-University of Sao Paulo School of Medicine, Sao Paulo, Brazil.
  • Kurian SM; Scripps Center for Organ Transplantation, Scripps Green Hospital, La Jolla, California.
Am J Transplant ; 19(12): 3356-3366, 2019 12.
Article in En | MEDLINE | ID: mdl-31152474
We determined peripheral blood (PB) and biopsy (Bx) RNA expression signatures in a Brazilian and US cohort of kidney transplant patients. Phenotypes assigned by precise histology were: acute rejection (AR), interstitial fibrosis/tubular atrophy/chronic rejection (CR), excellent functioning transplants (TX), and glomerulonephritis recurrence (GN). Samples were analyzed on microarrays and profiles from each cohort were cross-validated on the other cohort with similar phenotypes. We discovered signatures for each tissue: (1) AR vs TX, (2) CR vs TX, and (3) GN vs TX using the Random Forests algorithm. We validated biopsies signatures of AR vs TX (area under the curve [AUC] 0.97) and CR vs TX (AUC 0.87). We also validated both PB and Bx signatures of AR vs TX and CR vs TX with varying degrees of accuracy. Several biological pathways were shared between AR and CR, suggesting similar rejection mechanisms in these 2 clinical phenotypes. Thus, we identified gene expression signatures for AR and CR in transplant patients and validated them in independent cohorts of significantly different racial/ethnic backgrounds. These results reveal that there are strong unifying immune mechanisms driving transplant diseases and identified in the signatures discovered in each cohort, suggesting that molecular diagnostics across populations are feasible despite ethnic and environmental differences.
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Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukocytes, Mononuclear / Biomarkers / Ethnicity / Kidney Transplantation / Transcriptome / Graft Rejection / Kidney Failure, Chronic Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Am J Transplant Journal subject: TRANSPLANTE Year: 2019 Document type: Article Affiliation country: Brazil Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Leukocytes, Mononuclear / Biomarkers / Ethnicity / Kidney Transplantation / Transcriptome / Graft Rejection / Kidney Failure, Chronic Type of study: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Am J Transplant Journal subject: TRANSPLANTE Year: 2019 Document type: Article Affiliation country: Brazil Country of publication: United States