Verification of association of elevated serum ido enzyme activity with acute rejection and low cd4-atp levels with infection

Vikas R. Dharnidharka, Eihab Al Khasawneh, Sushil Gupta, Jonathan J. Shuster, Douglas W. Theriaque, Amir H. Shahlaee, Timothy J. Garrett

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

BACKGROUND: Both acute rejection (AR) and major infection events (MIE) can reduce long-term allograft survival. We assessed the simultaneous efficacy of serum and urine biomarker indoleamine 2,3-dioxygenase (IDO) enzyme activity and peripheral blood CD4-ATP levels for AR and MIE association, respectively. METHODS: We prospectively tested 217 blood and 167 urine serial samples, collected monthly for 12 months after transplantation from 29 consecutive children receiving a kidney transplant. The indoleamine 2,3-dioxygenase activity was assessed by mass spectrometry assays using the ratio of product L-kynurenine (kyn) to substrate tryptophan (trp). Kyn/trp ratios and blood CD4 T-cell ATP levels were correlated with AR, MIE, or stable group (no events) in the next 30 days. RESULTS: Using absolute cutoffs and allocating to samples to AR, MIE, or stable group, mean serum kyn/trp ratios were significantly elevated in the group that experienced AR (P=0.0007). Similarly, peripheral blood CD4-ATP levels were significantly lower in the group experiencing MIE (P=0.0351). Urine kyn/trp ratios and blood tacrolimus levels were not different between AR and stable groups. Within-subject analyses, accounting for repeated measures in subjects, also showed that, over time, serum kyn/trp ratios were higher before AR (P=0.031) and blood CD4-ATP levels were lower before MIE (P=0.008). CONCLUSIONS: These results from our pilot discovery group suggest that a panel of biomarkers together can predict overimmunosuppression or underimmunosuppression. Further independent validation in a multicenter cohort is suggested.

Original languageEnglish
Pages (from-to)567-572
Number of pages6
JournalTransplantation
Volume96
Issue number6
DOIs
StatePublished - Sep 2013

Keywords

  • IDO
  • Immuknow
  • Immune monitoring
  • Infection
  • Kidney
  • Pediatrics
  • Rejection
  • Transplantation

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