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. CONCLUSION: The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.
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. CONCLUSION: The Tact-to-Treg ratio is a valuable follow-up marker to detect HTx patients at risk of developing CAV.
Authors: Sonia Mirabet; Alvaro García-Osuna; Pablo Garcia de Frutos; Andreu Ferrero-Gregori; Vicens Brossa; Laura Lopez; Ruben Leta; Joan Garcia-Picart; Josep M Padro; José Luis Sánchez-Quesada; Juan Cinca; Jordi Ordonez-Llanos; Eulalia Roig Journal: Dis Markers Date: 2018-08-29 Impact factor: 3.434