Immunopathology of Loeys-Dietz Syndrome

NCT05472519 | Completed

• 1 other identifier: 69HCL22_0016
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

Loeys-Dietz Syndrome; immunology; T-Lymphocytes

Outcome Measures

Primary Outcomes (1)

• Percentage of circulating TFH lymphocyte subpopulation.

  Measured from the Blood samples of each patients / volunteers.

  Day 1

Secondary Outcomes (5)

• Intracellular pSmad2/3 labeling level of circulating TFH lymphocytes.

  Day 1

• Identification of Immuno-allergic pathologies

  Day 1

• Identification of serious infectious pathologies

  Day 1

• Identification of Vascular complications

  Day 1

• Identification morpho-skeletal complications

  Day 1

Study Arms (2)

Loeys-Dietz syndrome

OTHER

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

Biological: blood samples

Healthy Group

OTHER

Subjects aged ≥ 5 years.

Biological: blood samples

Interventions

blood samples 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

Healthy Group; Loeys-Dietz syndrome

Eligibility Criteria

• Age: 5 Years - 86 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• Persons under court protection.

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

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

Bron, 69677, France

Location

MeSH Terms

Conditions

Loeys-Dietz Syndrome

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2022
• First Posted: July 25, 2022
• Study Start: October 17, 2022
• Primary Completion: June 7, 2023
• Study Completion: June 7, 2023
• Last Updated: June 9, 2023

Record last verified: 2023-06

Locations

FR (1)