LYMPHGO: T and B Cells in Graves' Orbitopathy

Sponsor
University of Pisa (Other)
Overall Status
Completed
CT.gov ID
NCT03195296
Collaborator
(none)
20
4.9

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Other: No intervention

Study Design

Study Type:
Observational
Actual Enrollment :
20 participants
Observational Model:
Case-Only
Time Perspective:
Prospective
Official Title:
T and B Cells Infiltrating Orbital Tissues in Graves' Orbitopathy (GO) and Their Relation With GO Features
Actual Study Start Date :
Jan 1, 2017
Actual Primary Completion Date :
May 31, 2017
Actual Study Completion Date :
May 31, 2017

Arms and Interventions

Arm Intervention/Treatment
Graves' Orbitopathy

Patients with Graves' Orbitopathy subjected to orbital decompression

Other: No intervention
No intervention related to the study is foreseen

Outcome Measures

Primary Outcome Measures

  1. Correlation between lymphocytes infiltrating orbital tissue and GO activity [an average of 1 week]

    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

Secondary Outcome Measures

  1. Correlation between CD3-positive lymphocytes infiltrating orbital tissue and GO activity [an average of 1 week]

    Correlation between the number of CD3-positive lymphocytes infiltrating orbital tissues and the clinical activity score. The number of CD3 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD3 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

  2. Correlation between CD20-positive lymphocytes infiltrating orbital tissue and GO activity [an average of 1 week]

    Correlation between the number of CD20-positive lymphocytes infiltrating orbital tissues and the clinical activity score. The number of CD20 positive infiltrating lymphocytes is the sum of the number counted in four representative fields, following immunohistochemical staining for CD20 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

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 80 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients with Graves' orbitopathy subjected to orbital decompression
Exclusion Criteria:
  • None

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • University of Pisa

Investigators

  • Principal Investigator: Michele MarinĂ², MD, University of Pisa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
MarinĂ² Michele, Ricercatore (Assistant Professor), University of Pisa
ClinicalTrials.gov Identifier:
NCT03195296
Other Study ID Numbers:
  • LYMPHGO
First Posted:
Jun 22, 2017
Last Update Posted:
Feb 12, 2018
Last Verified:
Feb 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Feb 12, 2018