Hereditary Hemorrhagic Telangiectasia
Conditions
Brief summary
Hereditary hemorrhagic telangiectasia (HHT) results from genetic deregulation of angiogenesis. It is characterized by mucocutaneous telangiectasia responsible for recurrent epistaxis affecting quality of life (anaemia, iron deficiency, social distress). More rarely, HHT is complicated by the appearance of pulmonary, hepatic or cerebral arteriovenous malformations that can lead to serious complications: cerebrovascular accidents, cerebral abscesses, high output heart failure, and massive hemoptysis (1). The intensity of symptoms increases with age but with significant individual variability, even for the same mutation in the same family. Thus, while the mutations responsible for the disease have been identified, the pathophysiology is not fully understood because these mutations do not explain the great diversity of clinical presentations. Other factors not yet identified probably play an important role. Angiogenic T cells (TANG) are a newly individualized T cell population, defined by a CD4+CXCR4+CD31+ phenotype, which plays a key role in differentiating endothelial progenitors (2). In an earlier study, the investigators showed that patients with HHT had a decrease in CD4+ and CD8+ LT compared to a cohort of healthy subjects (3). They hypothesize that the lymphopenia mainly involves TANG, whose quantification could make it possible to assess the individual level of angiogenesis during HHT. The evaluation of the TANG levels could thus make it possible to personalize HHT management.
Interventions
BIOLOGICALBlood samples
* 5 mL dry tube to separate serum * Two 6 mL EDTA tubes for plasma separation * Eight 6 mL heparinized tubes for flow cytometry (quantification of TANG such as CD3+CD31+CXCR4+ and CEC) and quantification of angiogenesis markers.
OTHEREpistaxis charts
Three monthly epistaxis charts to be completed
Sponsors
Centre Hospitalier Universitaire Dijon
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Person who has given consent * Adult * Person capable of understanding spoken and written French Patient group: * Certain HHT (3 or 4 Curacao criteria - Appendix 2): * Recurring epistaxis * Telangiectasia of the skin or mouth * Family hereditary context * Arteriovenous visceral malformations * Causal mutation identified * Person capable of completing monthly epistaxis charts Control group : \- Control subjects will be matched to patients for age (+/- 6 years) and sex.
Exclusion criteria
* Person not affiliated to a national health insurance scheme * Pregnant or breastfeeding woman * Protected adult * Hemoglobin levels less than 9 g/dl in the last 15 days * Progressive or recent infectious disease, autoimmune disease or cancer (less than 6 months) * Immunosuppressive treatment in progress or recent (less than 6 months), including systemic steroid therapy. The use of inhaled or topical steroids is not an exclusion criterion. * Treatment in progress or stopped less than 6 months ago or to be introduced within the next 3 months of the following medications: * bevacizumab * tranexamic acid * dipeptidyl peptidase 4 inhibitors (diabetic patient) * beta-blockers (hypertensive patient)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Average monthly duration (in minutes) of epistaxis over the 3 months following inclusion | Through study completion, an average of 3 months |
| Number/mm3 of circulating TANG (CD3+CXCR4+CD31+) at inclusion. | At inclusion |
Countries
France
Outcome results
None listed