Immunopathology of Loeys-Dietz Syndrome

NCT ID: NCT05472519

Last Updated: 2023-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-17
• Study Completion Date: 2023-06-07

Brief Summary

Loeys-Dietz syndrome (LDS) is a rare vascular genetic disorder (estimated prevalence 1/25,000-1/100,000) due primarily to mutations in the Transforming growth factor beta (TGF-β) cytokine receptor 1 and 2 genes. In addition to a common vascular phenotype with Marfan syndrome (dilatation of the ascending aorta, arachnodactyly, lens dislocation), patients present specific malformations (bifid uvula, hypertelorism, tortuous arteries) and immuno-allergic manifestations (asthma, eczema, food allergy, eosinophilic esophagitis, chronic inflammatory bowel disease).

Pathophysiologically, LDS appears to be associated with hyperactivation of the intracellular TGF-β signaling pathway in a manner similar to Marfan syndrome, as evidenced by increased intracellular phosphorylated Smad2/3 (pSmad2/3) in lymphocytes. The immuno-allergic complications appear paradoxical because of the major immunosuppressive role of this cytokine on lymphoid and myeloid immune lineages.

The biological description of immunological abnormalities associated with LDS is based on a single 2013 study that found increased regulatory T (Treg) and Th2 lymphocyte polarizations, as well as increased circulating eosinophil and total IgE levels.

In order to better understand the underlying mechanisms, the investigators propose to perform a descriptive clinical-biological study to identify and study the immune subpopulations most impacted by the causative mutations of LDS.

Conditions

Loeys-Dietz Syndrome

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Loeys-Dietz syndrome

Patients aged ≥ 5 years with Loeys-Dietz syndrome with a diagnosis confirmed by the presence of a TGF-βR 1 or R2 mutation.

Group Type: OTHER

blood samples

Intervention Type: BIOLOGICAL

Only one visit for each participant: A large majority of visits will be part of patients' usual care.

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

blood samples

Intervention Type: BIOLOGICAL

Only one visit for each participant:

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

Healthy Group

Subjects aged ≥ 5 years.

Group Type: OTHER

blood samples

Intervention Type: BIOLOGICAL

Only one visit for each participant: A large majority of visits will be part of patients' usual care.

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

blood samples

Intervention Type: BIOLOGICAL

Only one visit for each participant:

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

Interventions

blood samples

Only one visit for each participant: A large majority of visits will be part of patients' usual care.

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

Intervention Type: BIOLOGICAL

blood samples

Only one visit for each participant:

• Medical examination : weight, gender, blood pressure, medical history
• Blood samples : 1 EDTA tube (3 mL) for CBC, 3 heparin tubes (3 × 7 mL) for frozen PBMC, 1 EDTA tube (3 mL) for frozen plasma

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

For patients with Loeys-Dietz syndrome:

• Patients aged ≥ 5 years with Loeys-Dietz syndrome with a diagnosis confirmed by the presence of a TGF-βR 1 or R2 mutation known to be pathogenic to patients.
• Free, informed and signed consent from the patient or both parents or legal guardians for minor patients.
• Patient affiliated to a social security system or similar.

For healthy volunteers:

• Subjects aged ≥ 5 years.
• Free, informed and signed consent of the witness, or if applicable of both parents or legal representatives for minors.
• Patient affiliated to a social security system or similar.

Exclusion Criteria

For patients with Loeys-Dietz syndrome:

• Patient with an evolving or recently healed (< 3 months) cancer that could alter the immunologic profile.
• Patient with an evolving or recently healed (< 3 months) infection that could alter the immunologic profile.
• Patient with a weight of less than 20 kg.
• Pregnant woman.
• Patient participating in another research study with an exclusion period exclusion period still in progress.

For healthy volunteers:

• Subject with an active or recently cured (< 3 months) cancer that could alter the immunologic profile.
• Subject with an active or recently healed (< 3 months) infection that could alter the immunological profile.
• Patient with a weight of less than 20 kg.
• Pregnant woman.
• Subject participating in another research study with an exclusion period exclusion period still in progress.
• Persons under court protection.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 86 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hôpital Femme-Mère-Enfant / Centre de Compétences pour le syndrome de Marfan et apparentés

Bron, , France

Countries

France

Other Identifiers

69HCL22_0016

Identifier Type: -

Identifier Source: org_study_id