TY - JOUR
T1 - Immune biomarker panel monitoring utilizing IDO enzyme activity and CD4 ATP levels
T2 - Prediction of acute rejection vs. viral replication events
AU - Dharnidharka, Vikas R.
AU - Gupta, Sushil
AU - Al Khasawneh, Eihab
AU - Haafiz, Allah
AU - Shuster, Jonathan J.
AU - Theriaque, Douglas W.
AU - Shahlaee, Amir H.
AU - Garrett, Timothy J.
PY - 2011/5
Y1 - 2011/5
N2 - Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.
AB - Infections have become as important an event as acute rejection posttransplant for long-term allograft survival. Less invasive biomarkers tested so far predict risk for one event or the other, not both. We prospectively tested blood and urine monthly for 12 months posttransplant from children receiving a kidney transplant. The IDO enzyme pathway was assessed by MS assays using the ratio of product l-kyn to substrate trp. Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with acute rejection or major infection events or stable group (no events) in the next 30 days. The 25 subjects experienced six discrete episodes of acute rejection in five subjects and 16 discrete events of major infection in 14 subjects (seven BK viruria, six cytomegaloviremia, one EB and cytomegaloviremia, and two transplant pyelonephritis). Mean serum kyn/trp ratios were significantly elevated in the group that experienced acute rejection (p = 0.02). Within-subject analyses revealed that over time, urine kyn/trp ratios showed an increase (p = 0.01) and blood CD4-ATP levels showed a decrease (p = 0.007) prior to a major infection event. These pilot results suggest that a panel of biomarkers together can predict over- or under-immunosuppression, but need independent validation.
KW - IDO
KW - Immuknow
KW - immune monitoring
KW - infection
KW - kidney
KW - pediatrics
KW - rejection
KW - transplantation
UR - http://www.scopus.com/inward/record.url?scp=79954989973&partnerID=8YFLogxK
U2 - 10.1111/j.1399-3046.2011.01485.x
DO - 10.1111/j.1399-3046.2011.01485.x
M3 - Article
C2 - 21492353
AN - SCOPUS:79954989973
SN - 1397-3142
VL - 15
SP - 321
EP - 328
JO - Pediatric transplantation
JF - Pediatric transplantation
IS - 3
ER -