[HTML][HTML] Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection

W Zhang, Z Yi, C Wei, KL Keung, Z Sun, C Xi… - JCI insight, 2019 - ncbi.nlm.nih.gov
W Zhang, Z Yi, C Wei, KL Keung, Z Sun, C Xi, C Woytovich, S Farouk, L Gallon, MC Menon
JCI insight, 2019ncbi.nlm.nih.gov
Commonly available clinical parameters fail to predict early acute cellular rejection (EAR,
occurring within 6 months after transplant), a major risk factor for graft loss after kidney
transplantation. We performed whole-blood RNA sequencing at the time of transplant in 235
kidney transplant recipients enrolled in a prospective cohort study (Genomics of Chronic
Allograft Rejection [GoCAR]) and evaluated the relationship of pretransplant transcriptomic
profiles with EAR. EAR was associated with downregulation of NK and CD8+ T cell gene …
Abstract
Commonly available clinical parameters fail to predict early acute cellular rejection (EAR, occurring within 6 months after transplant), a major risk factor for graft loss after kidney transplantation. We performed whole-blood RNA sequencing at the time of transplant in 235 kidney transplant recipients enrolled in a prospective cohort study (Genomics of Chronic Allograft Rejection [GoCAR]) and evaluated the relationship of pretransplant transcriptomic profiles with EAR. EAR was associated with downregulation of NK and CD8+ T cell gene signatures in pretransplant blood. We identified a 23-gene set that predicted EAR in the discovery (n= 81, and AUC= 0.80) and validation (n= 74, and AUC= 0.74) sets. Exclusion of recipients with 5 or 6 HLA donor mismatches increased the AUC to 0.89. The risk score derived from the gene set was also significantly associated with acute cellular rejection after 6 months, antibody-mediated rejection and/or de novo donor-specific antibodies, and graft loss in a cohort of 154 patients, combining the validation set and additional GoCAR patients with surveillance biopsies between 6 and 24 months (n= 80) posttransplant. This 23-gene set is a potentially important new tool for determination of the recipient’s immunological risk before kidney transplantation, and facilitation of an individualized approach to immunosuppressive therapy.
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