Immunological Follow-up of Patients With Basedow's Orbitopathy (SIPO)

Immunological Follow-up of Patients With Basedow's Orbitopathy : SIPO

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.

Study Overview

• Status: Completed
• Conditions: Graves Orbitopathy

• Study Type: Observational
• Enrollment (Actual): 15

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34295
    • Uhmontpellier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients with Graves' disease

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantify the subpopulations of CD4, CD8, Th, Treg and B-cells	Quantify the subpopulations of CD4, CD8, Th, Treg and B-cells in the peripheral blood of subjects with Graves' disease	1 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the frequency and activation of lymphocyte subpopulations	Compare the frequency and activation of lymphocyte subpopulations in peripheral blood regarding TRAK levels	1 day
Compare the phenotypic characteristics of Tregs present	Compare the phenotypic characteristics of Tregs present in the peripheral blood of Graves' disease patients with Tregs in the peripheral blood of RA patients (previous laboratory data).	1 day

Collaborators and Investigators

• Sponsor: University Hospital, Montpellier
• Investigators: Study Director: Yves-Marie PERS, MD,PhD, University Hospital, Montpellier

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2020
• Primary Completion (ACTUAL): November 1, 2021
• Study Completion (ACTUAL): November 30, 2021

Study Registration Dates

• First Submitted: October 26, 2020
• First Submitted That Met QC Criteria: October 26, 2020
• First Posted (ACTUAL): October 30, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Immune monitoring; Graves orbitopathy; TRAK
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Endocrine System Diseases; Genetic Diseases, Inborn; Thyroid Diseases; Eye Diseases, Hereditary; Graves Disease; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Graves Ophthalmopathy
• Other Study ID Numbers: RECHMPL20_0597

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: NC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No