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.
| Original language | English (US) |
|---|---|
| Article number | e127543 |
| Journal | JCI Insight |
| Volume | 4 |
| Issue number | 11 |
| DOIs | |
| State | Published - Jun 6 2019 |
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ASJC Scopus subject areas
- Medicine(all)
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Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection. / Zhang, Weijia; Yi, Zhengzi; Wei, Chengguo; Keung, Karen L.; Sun, Zeguo; Xi, Caixia; Woytovich, Christopher; Farouk, Samira; Gallon, Lorenzo; Menon, Madhav C.; Magee, Ciara; Najafian, Nader; Samaniego, Milagros D.; Djamali, Arjang; Alexander, Stephen I.; Rosales, Ivy A.; Smith, Rex Neal; O’Connell, Philip J.; Colvin, Robert; Cravedi, Paolo; Murphy, Barbara.
In: JCI Insight, Vol. 4, No. 11, e127543, 06.06.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - Pretransplant transcriptomic signature in peripheral blood predicts early acute rejection
AU - Zhang, Weijia
AU - Yi, Zhengzi
AU - Wei, Chengguo
AU - Keung, Karen L.
AU - Sun, Zeguo
AU - Xi, Caixia
AU - Woytovich, Christopher
AU - Farouk, Samira
AU - Gallon, Lorenzo
AU - Menon, Madhav C.
AU - Magee, Ciara
AU - Najafian, Nader
AU - Samaniego, Milagros D.
AU - Djamali, Arjang
AU - Alexander, Stephen I.
AU - Rosales, Ivy A.
AU - Smith, Rex Neal
AU - O’Connell, Philip J.
AU - Colvin, Robert
AU - Cravedi, Paolo
AU - Murphy, Barbara
PY - 2019/6/6
Y1 - 2019/6/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85070659158&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85070659158&partnerID=8YFLogxK
U2 - 10.1172/jci.insight.127543
DO - 10.1172/jci.insight.127543
M3 - Article
C2 - 31167967
AN - SCOPUS:85070659158
VL - 4
JO - JCI insight
JF - JCI insight
SN - 2379-3708
IS - 11
M1 - e127543
ER -