Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation

Transplant Proc. 2012 Nov;44(9):2645-8. doi: 10.1016/j.transproceed.2012.09.036.

Abstract

Background: The indoleamine, 2-3 dioxygenase (IDO) is an inducible intracellular enzyme with immunosuppressive effects mainly on lymphocyte populations. It has been postulated that indirect determination of IDO serum activity may be a marker of renal graft rejection, but its potential usefulness in heart transplantation (HT) is unknown.

Methods: This longitudinal study included 98 HT patients (83% males) who survived ≥1 year. Mean age was 54.14 ± 11.57 years. Serum IDO activity was analyzed one month after HT by means of high performance liquid chromatography and correlated with the cumulative incidence of acute rejection (AR) during one-year follow-up. AR was defined as biopsy-proven ≥ ISHLT grade 2R rejection or empirically treated non-biopsy-proven rejection. The study sample was divided into two groups: AR group (n = 51), including patients who experienced at least one AR episode during the first year after HT; No-AR group (N = 47), including the remaining patients.

Results: Mean serum IDO activity one month after HT was significantly higher (P = .021) in the AR group (3.32 ± 1.56) than in the no-AR group (2.62 ± 1.35). No significant association between serum IDO activity and gender (male: 3.1 ± 1.56, women: 2.43 ± 0.99, P = .092), recipient age (r = -.07, P = .943) or donor age (r = 0.108, P = 0.293) was observed. By means of binary logistic regression, an odds ratio of 1.4 [CI 95%: 1.033-1.876, P = .03] per unit increase of act-IDO was estimated, with no significant modification upon forced adjustment for age and sex. Mean glomerular filtration rate 1 month after HT was 67.01 ± 28.51 mL/min/m(2). No significant correlation between this parameter and serum IDO activity was observed (r = .160, P = .117).

Conclusions: Our study suggests that serum IDO activity one month after HT might be associated with a higher risk of AR during one-year follow-up. This association seems to be independent of recipient gender, age or renal function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid
  • Female
  • Glomerular Filtration Rate
  • Graft Rejection / blood
  • Graft Rejection / enzymology*
  • Graft Rejection / epidemiology
  • Graft Rejection / immunology
  • Graft Survival*
  • Heart Transplantation / adverse effects
  • Heart Transplantation / immunology*
  • Humans
  • Incidence
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / blood*
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Odds Ratio
  • Predictive Value of Tests
  • Risk Assessment
  • Risk Factors
  • Spain / epidemiology
  • Time Factors
  • Treatment Outcome
  • Up-Regulation

Substances

  • Biomarkers
  • Indoleamine-Pyrrole 2,3,-Dioxygenase