Immunological Effects of Iron Supplementation in HHT Disease

Summary

Hereditary haemorrhagic telangiectasia (HHT), is a rare genetic vascular disorder with autosomal dominant inheritance. Its prevalence is estimated at approximately 1 in 6,000 individuals in France. Clinical manifestations include recurrent nosebleeds (epistaxis), cutaneous telangiectasias, and visceral arteriovenous malformations (AVMs) that may affect the lungs, gastrointestinal tract, liver, and brain.

Beyond vascular abnormalities, patients often present with a decrease in circulating T lymphocytes (T-cell lymphopenia), which can be profound but remains unexplained. There is also a distinct infectious risk profile associated with the disease: brain abscesses in the presence of pulmonary AVMs (pAVMs), and osteoarticular infections in patients with the longest durations of epistaxis. However, no definitive correlation has been established between T-cell lymphopenia and infection risk.

Iron-deficiency anemia is a frequent complication in HHT, affecting about 50% of patients, with a mean age of onset around 36 years. Its prevalence increases with age. These patients typically require prolonged and high-dose iron supplementation, administered either orally or intravenously, which may expose them to side effects not observed in other clinical contexts. In a previous study, we identified a correlation between the level of iron supplementation (none, oral, or intravenous) and the severity of T-cell lymphopenia.

This association may be explained by two potential mechanisms linking iron metabolism to immune function:

* A direct toxic effect of iron on immune system homeostasis
* Impaired lymphocyte production resulting from iron deficiency, with the type of supplementation serving as an indirect marker of deficiency severity We propose a prospective study designed to differentiate between these two hypotheses. The aim of the study is to characterize the impact of iron deficiency and iron supplementation on the immune system of patients with HHT.

Conditions

• Hereditary Haemorrhagic Telangiectasia

Interventions

BIOLOGICAL

Blood test at D0

Six extra blood collection tubes (28 mL) will be drawn during the visit (D0), in addition to the routine blood samples, at the blood collection center

BIOLOGICAL

Blood test at D+3 months

six extra blood collection tubes (28 mL) will be drawn during the visit (D+3 months) for group 3 patients, in addition to the routine blood samples, at the blood collection center

Sponsors & Collaborators

• Hospices Civils de Lyon

  lead OTHER

Study Design

Allocation

NON_RANDOMIZED

Purpose

HEALTH_SERVICES_RESEARCH

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

99 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-09-24

Primary Completion

2028-12-31

Completion

2028-12-31

Countries

• France

Study Locations