Clinical trial NCT04610723: Immunological Follow-up of Patients With Basedow's Orbitopathy
Official title: Immunological Follow-up of Patients With Basedow's Orbitopathy : SIPO
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Graves Orbitopathy
Keywords: Graves orbitopathy
TRAK
Immune monitoring
Lead sponsor: University Hospital, Montpellier
Sponsor class: OTHER
First posted: 2020-10-30
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with Graves' disease

Brief summary: Graves' disease is characterized by the combination of anti-TSH receptor antibodies (Thyroid-Stimulating Hormone or thyroidotropic hormone), specific to this disease, with inconsistent symptoms such as hyperthyroidism, orbitopathy, goiter, or myxedema dermatological involvement. The activation of TSH receptors (RTSH) by these antibodies (known as "TRAK") causes the secretion of thyroid hormones as well as the development of the thyroid gland, responsible for a goiter. The cellular infiltrate responsible for the goiter consists mainly of T-lymphocytes but also of activated B lymphocytes secreting TRAK. Although Graves' disease is antibody mediated, cytokine secretion by Th1 therefore seems essential to pathogenesis. The treatment of orbitopathy requires primarily euthyroidism and the discontinuation of smoking. Despite these measures, moderate to severe attacks may require immunomodulatory treatment to limit local inflammation. This treatment is currently based on a first-line corticosteroid treatment (per os or preferably by weekly intravenous infusions). In the context of inadequate response, the therapeutic strategy is not very well established since some immunosuppressive treatments targeting B-cells or T- cells have been studied but with little benefit.

Many new concepts concerning immune tolerance and autoimmunity have emerged in recent years, particularly in Graves' disease, with sometimes complex cellular interactions. Certain mechanisms could occur either independently or in combination: i) modulation of T cell activation, differentiation and apoptosis; ii) inhibition of BL maturation and immunoglobulin production; iii) alteration of the balance between T helper (Th)-17 and T regulatory lymphocytes (Treg), by promoting Treg differentiation and inhibiting Th17 differentiation.


Eligibility criteria: Inclusion criteria:

* Patients aged 18 to 80 years included
* Subjects with Grave's disease and unsuccessful or intolerant to corticosteroid bolus therapy (EUGOGO protocol)
* Subjects with positive TRAKs

Exclusion criteria:

* Current treatment or within 6 months before inclusion by anti-CD20 monoclonal antibodies
* Current treatment or in the month prior to inclusion with corticosteroids \>10 mg/day (oral or intravenous)

Primary outcomes:
measure: Quantify the subpopulations of CD4, CD8, Th, Treg and B-cells
timeFrame: 1 day
Secondary outcomes:
measure: Compare the frequency and activation of lymphocyte subpopulations
timeFrame: 1 day
measure: Compare the phenotypic characteristics of Tregs present
timeFrame: 1 day
Other outcomes:
Locations:
city: Montpellier
country: France
facility: Uhmontpellier
Study officials:
affiliation: University Hospital, Montpellier
name: Yves-Marie PERS, MD,PhD
role: STUDY_DIRECTOR
References: