NCT03195296: LYMPHGO

T and B Cells in Graves' Orbitopathy

Completed Last updated 12 February 2018

What this trial tests

trial testing No intervention in Graves Ophthalmopathy in 20 participants. Completed in 31 May 2017.

Timeline

1 January 2017

Primary endpoint
31 May 2017

31 May 2017

Quick facts

Lead sponsor	University of Pisa
Status	Completed
Study type	OBSERVATIONAL
Enrollment	20
Start date	1 January 2017
Primary completion	31 May 2017
Estimated completion	31 May 2017

Drugs / interventions tested

• No intervention

Conditions studied

• Graves Ophthalmopathy — all drugs for Graves Ophthalmopathy →

Sponsor

University of Pisa

Who can join

Adults 18 to 80, any sex, with Graves Ophthalmopathy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.