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Updated: May 30, 2026

Mouse Model of Alloimmune-induced Vascular Rejection and Transplant Arteriosclerosis
Published on: May 17, 2015
Assessment of immunological markers as mediators of graft vasculopathy development in heart transplantation
1Cardiology Department, Hospital de Sant Pau, Institute of Byomedical Research (IIB-Sant Pau), Autonomous University of Barcelona, Barcelona, Spain. SMirabet@santpau.cat
Insights
The Th1/Treg ratio may help detect cardiac allograft vasculopathy (CAV) early after heart transplantation (HT). Monitoring this immune marker could identify patients at risk for CAV, a major cause of death post-HT.
Area of Science:
- Immunology
- Cardiology
- Transplantation Medicine
Background:
- Cardiac allograft vasculopathy (CAV) is a leading cause of death after heart transplantation (HT).
- Current diagnosis via coronary angiography often occurs when CAV is advanced.
- Early detection requires noninvasive markers for immune monitoring.
Purpose of the Study:
- To assess immunologic markers, specifically the Th1/Treg ratio, as mediators of CAV development in HT recipients.
- To evaluate the potential of the Th1/Treg ratio as an early detection marker for CAV.
Main Methods:
- Flow cytometry was used to analyze peripheral blood mononuclear cell populations in de novo HT recipients.
- Key markers included CD3, CD4, CD8, CD19, CD56, Th1 (CD3+IFNγ+), and Treg (CD4+CD25(high)FoxP3+).
- A control group of post-HT patients and healthy subjects was included for comparison.
Main Results:
- CAV-related events over 2 years correlated with the Th1/Treg ratio.
- An increased percentage of Th1 lymphocytes was observed during follow-up.
- Higher Th1/Treg ratios were associated with increased acute rejection scores and CAV incidence.
Conclusions:
- The Th1/Treg ratio may serve as a valuable marker for monitoring T-cell responses post-HT.
- Changes in the Th1/Treg ratio could aid in the early identification of patients at risk for CAV.
- Further studies with longer follow-up are needed to validate these preliminary findings.
Abstract:
Heart transplantation (HT) remains the treatment of choice for patients with end-stage heart failure. Cardiac allograft vasculopathy (CAV), a diffuse form of coronary atherosclerosis, is the major cause of death after the first year of HT. CAV is thought to be multifactorial in origin. Although nonimmune factors may play a role in CAV development, it is primarily an immune-mediated disease. CAV is diagnosed by routine annual coronary angiography, and usually when diagnosed, the disease is advanced. There is a need to develop noninvasive surrogate markers for early detection. For this purpose, careful immune monitoring and graft histologic assessment are mandatory. The main objective of this study was the assessment of immunologic markers as mediators of CAV development in HT. Flow cytometry was performed to assess peripheral blood mononuclear cell populations forming CD3, CD4, CD8, CD19, CD56, Th1 (CD3+IFNγ+) or Treg (CD4+CD25(high)FoxP3+) markers among 20 de novo HT recipients. The control group included 13 patients who were more than 2 years post-HT (four with and nine without CAV) as well as 20 healthy subjects. CAV-related events over 2 years' follow-up correlated with the Th1/Treg ratio. An increased Th1 lymphocyte percentage was detected over the follow-up. Patients with medium and high Th1/Treg ratios showed higher acute rejection scores as well as greater incidences of CAV. These results indicated that the Th1/Treg ratio may represent a valuable marker to monitor allospecific T-cell responses in peripheral blood. Changes in the Th1/Treg ratio may help in the early detection of patients at risk for CAV. More studies with longer follow-up are needed to confirm these preliminary results.
