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NCT Number: NCT05472519

Immunopathology of Loeys-Dietz Syndrome

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.

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Key information

Conditions

Loeys-Dietz Syndrome Abnormalities, Multiple Aneurysm Aortic Aneurysm Aortic Diseases Cardiovascular Diseases Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Craniofacial Abnormalities Genetic Diseases, Inborn Musculoskeletal Abnormalities Musculoskeletal Diseases Vascular Diseases

Age range

5 year–86 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

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

Bron, 69677, France

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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

Primary outcomes

  1. Percentage of circulating TFH lymphocyte subpopulation.

    Time frame: Day 1

    Measured from the Blood samples of each patients / volunteers.

Secondary outcomes

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

    Time frame: Day 1

    Measured from the Blood samples of each patients / volunteers.

  2. Identification of Immuno-allergic pathologies

    Time frame: Day 1

    Identification of Immuno-allergic, serious infectious pathologies (diagnostic criteria, severity criteria, treatment, current activity) in LDS patients.

  3. Identification of serious infectious pathologies

    Time frame: Day 1

    Identification of serious infectious pathologies (diagnostic criteria, severity criteria, treatment, current activity) in LDS patients.

  4. Identification of Vascular complications

    Time frame: Day 1

    Identification of Vascular, morpho-skeletal complications (diagnostic criteria, severity criteria, treatment, current activity) current course) in patients with LDS.

  5. Identification morpho-skeletal complications

    Time frame: Day 1

    Identification of morpho-skeletal complications (diagnostic criteria, severity criteria, treatment, current activity) current course) in patients with LDS.

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Acronym: I-LoDiS

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Jul 25, 2022
Registry last updated
Jun 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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