title: CD4+CD45RO+CD25-/lowCD127+: CD4+CD45RO+CD25hiCD127-/low Ratio in Peripheral Blood: A Useful Biomarker to Detect Cardiac Allograft Vasculopathy in Heart Transplanted Patients.
abstract: BACKGROUND
  Cardiac allograft vasculopathy (CAV) is a major limitation in long-term graft survival after heart transplantation (HTx). Its prediction and detection at an early stage is a challenge because an accurate, minimally invasive blood test is lacking. The aim of this study was to analyze the relationship of Tact (CD4CD45ROCD25-CD127) cells, Th1 cells, and thymus-derived regulatory (Treg) (CD4CD45ROCD25CD127) cells in peripheral blood with the development of CAV in HTx patients.
  
  
  METHODS
  First, we performed a cross-sectional study in 29 patients at least 2 years after HTx, 17 with CAV and 12 without CAV. We then prospectively followed a group of 38 patients for 2 years immediately after HTx surgery. In both groups, we analyzed the relationship between CAV and the effector-to-regulatory T cell ratio.
  
  
  RESULTS
  In the cross-sectional study, patients with CAV showed statistically significant higher values of Th1-to-FoxP3Treg and Tact-to-CD127Treg ratios than non-CAV patients, with P less than 0.01 and P less than 0.001, respectively. Receiver operating characteristic curve analysis showed that the Tact:CD127Treg ratio was a potential biomarker of CAV, clearly discriminating CAV and non-CAV patients (area under curve [AUC] = 0.955; P = 0.001). In the prospective part of the study, we monitored the Th1:FoxP3Treg and Tact:CD127Treg ratios using the best tradeoff between anterior receiver operating characteristic sensitivity and specificity as a cutoff. Changes in the Tact:CD127Treg ratio were detected earlier than changes in the Th1:FoxP3Treg ratio. Both ratios were higher in HTx patients with CAV.
  
  
  CONCLUSIONS
  The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.
authors.affiliation: 1 Department of Immunology, Institut Recerca Sant Pau Hospital, Barcelona, Spain. 2 Department of Immunology, Autonomous University of Barcelona, Barcelona, Spain. 3 Department of Cardiology, Sant Pau Hospital, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Roldán
authors.forename: Sònia
authors.initials: S
authors.lastname: Mirabet
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecilia
authors.forename: Vicens
authors.initials: V
authors.lastname: Brossa
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Roig
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martín
authors.forename: Carmen
authors.initials: C
authors.lastname: Gelpí
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis* / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D053699:Interleukin-7 Receptor alpha Subunit / Q000097:blood*; D017493:Leukocyte Common Antigens / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D053699:Interleukin-7 Receptor alpha Subunit; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human