title: Indoleamine, 2-3 dioxygenase activity could be an early marker of graft rejection in heart transplantation.
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.
authors.affiliation: Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Suarez-Fuentetaja
authors.forename: N
authors.initials: N
authors.lastname: Domenech-Garcia
authors.forename: M J
authors.initials: MJ
authors.lastname: Paniagua-Martin
authors.forename: R
authors.initials: R
authors.lastname: Marzoa-Rivas
authors.forename: E
authors.initials: E
authors.lastname: Barge-Caballero
authors.forename: Z
authors.initials: Z
authors.lastname: Grille-Cancela
authors.forename: J
authors.initials: J
authors.lastname: Pombo-Otero
authors.forename: J
authors.initials: J
authors.lastname: Muñiz-García
authors.forename: A
authors.initials: A
authors.lastname: Castro-Beiras
authors.forename: M G
authors.initials: MG
authors.lastname: Crespo-Leiro
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000097:blood / Q000201:enzymology* / Q000453:epidemiology / Q000276:immunology; D006085:Graft Survival; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D015994:Incidence; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase