T and B Cells in Graves' Orbitopathy

NCT03195296 | Completed

• 1 other identifier: LYMPHGO
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

Graves orbitopathy (GO) is an inflammatory eye disease associated in 95% of patients with Graves' hyperthyroidism (GH), in \~3-4% with hypothyroid autoimmune thyroiditis, and in \~1-2% with thyroid autoimmunity in the absence of thyroid dysfunction, the former known as euthyroid GO. The pathogenesis of GO is autoimmune, with the TSH-receptor being considered the major autoantigen, thereby establishing a pathogenetic link between the thyroid and orbital tissue. Thus, TSH-receptor is expressed by orbital fibroblasts, where it forms a complex with the IGF-1 receptor. Unlike GH, which is notoriously caused by TSH-receptor stimulating autoantibodies, GO is believed to reflect cell-mediated autoimmunity, as suggested by studies showing a Th1-like pattern of cytokine release by primary cultures of orbital infiltrating lymphocytes from GO patients. On the other hand, a role of B lymphocytes has emerged in recent years based on the observation that the anti-CD20 monoclonal antibody rituximab has a beneficial effect on GO activity, as demonstrated by a recent randomized clinical trial in which rituximab was compared with intravenous glucocorticoids (GC), being the former the standard treatment of moderately-severe GO. The explanation for the findings was that B lymphocytes are involved in the pathogenesis of GO as antigen-presenting cells. However, in spite of the above mentioned promising observations, another randomized clinical trial in which rituximab was compared with placebo provided opposite results. Thus, rituximab had no effect at all on GO. Data from the two studies were confronted and major differences between the two cohorts emerged, especially concerning GO activity, leading to the conclusion that rituximab may be effective for active, but not for inactive GO. Rituximab has been employed also for autoimmune diseases other than GO, including type 1 diabetes. In the former, it was shown that the effectiveness of rituximab paralleled the presence of CD20-positive infiltrating lymphocytes in pancreas islets. We therefore postulated that something similar may occur in GO, because of which we planned the present, perspective, observational study, aimed at determining the presence and immunohistochemical features of lymphocytes infiltrating orbital tissues in patients with GO and to relate them with the clinical features of GO.

Conditions

Graves Ophthalmopathy

Outcome Measures

Primary Outcomes (1)

• Correlation between lymphocytes infiltrating orbital tissue and GO activity

  Correlation between the number of lymphocytes infiltrating orbital tissues and the clinical activity score. The number of infiltrating lymphocytes is the sum of the number counted in four representative fields. The clinical activity score comprises 7 items (eyelid edema, conjuctival redness, eyelid redness, chemosis, caruncle edema, spontaneous eye pain, gaze-evoked eye pain), resulting in a numerical score going from 1 to 7

  an average of 1 week

Secondary Outcomes (2)

• Correlation between CD3-positive lymphocytes infiltrating orbital tissue and GO activity

  an average of 1 week

• Correlation between CD20-positive lymphocytes infiltrating orbital tissue and GO activity

  an average of 1 week

Study Arms (1)

Graves' Orbitopathy

Patients with Graves' Orbitopathy subjected to orbital decompression

Other: No intervention

Interventions

No intervention OTHER

No intervention related to the study is foreseen

Graves' Orbitopathy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with Graves' orbitopathy to undergo orbital decompression

You may qualify if:

• Patients with Graves' orbitopathy subjected to orbital decompression

You may not qualify if:

• None

Sponsors & Collaborators

• University of Pisa: lead

Biospecimen

Retention: SAMPLES WITHOUT DNA

Fibroadipose orbital tissue samples

MeSH Terms

Conditions

Graves Ophthalmopathy

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Study Officials

• Michele Marinò, MD

  University of Pisa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ricercatore (Assistant Professor)

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 22, 2017
• Study Start: January 1, 2017
• Primary Completion: May 31, 2017
• Study Completion: May 31, 2017
• Last Updated: February 12, 2018

Record last verified: 2018-02

Data Sharing

• IPD Sharing: Will not share