Immunological Follow-up of Patients With Basedow's Orbitopathy

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT04610723

Acronym

SIPO

Enrollment

Registered

2020-10-30

Start date

2020-11-01

Completion date

2021-11-30

Last updated

2022-01-11

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Graves Orbitopathy

Keywords

Graves orbitopathy, TRAK, Immune monitoring

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to 80 Years

Healthy volunteers

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)

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Compare the frequency and activation of lymphocyte subpopulations	1 day	Compare the frequency and activation of lymphocyte subpopulations in peripheral blood regarding TRAK levels
Compare the phenotypic characteristics of Tregs present	1 day	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).

Countries

France

Outcome results