Unravelling the role of trained immunity in cardiac allograft vasculopathy

Unravelling the role of trained immunity in cardiac allograft vasculopathy - Trained immunity in heart transplantation

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON56885

Enrollment

300

Registered

2024-03-12

Start date

2025-03-24

Completion date

Unknown

Last updated

2026-01-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac allograft vasculopathy narrowing of the coronary arteries. Transplant heart blood-vessel narrowing

Interventions

Not applicable.

Eligibility

Age

2 Years to 99 Years

Inclusion criteria

Inclusion criteria: Patient groups: - Children and adults undergoing HTx (Primary objective 1) or - Pediatric and adult HTx patients 5-10 years post-HTx or * 10 years post-HTx (Primary objective 2 and secondary objectives). - Written informed consent. Control group: - Healthy adolescents enrolled in the Whistler birth cohort study. - Written informed consent, including transfer of data and blood samples to the Trained immunity in heart transplantation study team at the Erasmus MC.

Exclusion criteria

Exclusion criteria: Acute infection (fever >38.5*C and/or clinical infectious symptoms).

Design outcomes

Primary

Measure	Time frame
a) Trained immunity: Functional testing of trained immunity is performed using previously established protocols. Levels of the inflammatory cytokines IL1β, IL6 and TNF are measured in culture supernatants upon ex vivo stimulation of whole blood with trained immunity stimuli such as the TLR2 and TLR4 ligands Pam3CysK4 and lipopolysaccharide (LPS), and NLRP3-inflammasome activating cholesterol crystals. The cytokine levels are continuous variables. b) CAV grading: CAV grading is performed using computed tomography (CT) coronary angiograms, including fractional flow reserve measurement, according to international society for heart and lung transplantation guidelines (ISHLT) and established local protocols. CAV grade is an ordinal variable (grade 0-3).	—

Measure

Time frame

a) Trained immunity: Functional testing of trained immunity is performed using previously established protocols. Levels of the inflammatory cytokines IL1β, IL6 and TNF are measured in culture supernatants upon ex vivo stimulation of whole blood with trained immunity stimuli such as the TLR2 and TLR4 ligands Pam3CysK4 and lipopolysaccharide (LPS), and NLRP3-inflammasome activating cholesterol crystals. The cytokine levels are continuous variables. b) CAV grading: CAV grading is performed using computed tomography (CT) coronary angiograms, including fractional flow reserve measurement, according to international society for heart and lung transplantation guidelines (ISHLT) and established local protocols. CAV grade is an ordinal variable (grade 0-3).

—

Secondary

Measure	Time frame
a) Innate and adaptive immune cell phenotypes (secondary objectives): Compre-hensive phenotyping of circulating immune cells will be performed using: • Multi-color flow cytometry of circulating monocytes, dendritic cells, T-cells and B-cells (naïve versus effector and memory). Phenotyping will include the expression of activation markers, inflammatory factors and adhesion proteins relevant for CAV development, using previously established protocols. Leukocyte subset frequencies and expression levels of activation markers, inflammatory factors and adhesion proteins are continuous varia-bles. • Morphological phenotyping of circulating leukocytes, using DeepCell technology. Morphological parameters are continuous variables. b) Clinical determinants of CAV development: Routine clinical parameters with rele-vance for CAV development and the study objectives will be included in the study database. These parameters include: age, gender, underlying cardiac dis-ease, HTx date, AB0 blood group and antibodies, HLA antibodies / mismatch, re-jection episodes, viral reactivation episodes and immune status, immunosup-pression, and cardiometabolic determinants (dyslipidemia, obesity, dysglycemia, hypertension).	—

Measure

Time frame

a) Innate and adaptive immune cell phenotypes (secondary objectives): Compre-hensive phenotyping of circulating immune cells will be performed using: • Multi-color flow cytometry of circulating monocytes, dendritic cells, T-cells and B-cells (naïve versus effector and memory). Phenotyping will include the expression of activation markers, inflammatory factors and adhesion proteins relevant for CAV development, using previously established protocols. Leukocyte subset frequencies and expression levels of activation markers, inflammatory factors and adhesion proteins are continuous varia-bles. • Morphological phenotyping of circulating leukocytes, using DeepCell technology. Morphological parameters are continuous variables. b) Clinical determinants of CAV development: Routine clinical parameters with rele-vance for CAV development and the study objectives will be included in the study database. These parameters include: age, gender, underlying cardiac dis-ease, HTx date, AB0 blood group and antibodies, HLA antibodies / mismatch, re-jection episodes, viral reactivation episodes and immune status, immunosup-pression, and cardiometabolic determinants (dyslipidemia, obesity, dysglycemia, hypertension).

—

Countries

Netherlands

Contacts

Public ContactH.S. Schipper

Erasmus MC, Universitair Medisch Centrum Rotterdam

vc.kindercardiologie@erasmusmc.nl010-7040704

Outcome results

None listed

Source: NL-OMON (via WHO ICTRP)