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Original Investigation
June 2018

Association of T and B Cells Infiltrating Orbital Tissues With Clinical Features of Graves Orbitopathy

Author Affiliations
  • 1Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy
  • 2Department of Surgical, Medical and Molecular Pathology, Pathology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy
  • 3Department of Pathology, Division of Immunology, Johns Hopkins School of Medicine, Baltimore, Maryland
  • 4Department of Surgical, Medical and Molecular Pathology, Ophthalmopathy Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy
  • 5Obesity and Diabetes Clinical Research Section, Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona
  • 6Department of Surgical, Medical and Molecular Pathology, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy
  • 7Department of Clinical and Experimental Medicine, Endocrinology Unit II, University of Pisa and University Hospital of Pisa, Pisa, Italy
JAMA Ophthalmol. 2018;136(6):613-619. doi:10.1001/jamaophthalmol.2018.0806
Key Points

Question  Does the phenotype of Graves orbitopathy, especially its activity, reflect the extent and features of the lymphocytic infiltrate of orbital tissues?

Findings  In this cohort study conducted in 20 consecutive patients with Graves orbitopathy, an association between the clinical activity score and orbital lymphocytes was found, analyzed as total number and main lymphoid subsets, both in a simple and multiple regression model.

Meaning  These findings suggest a correlation between T and B lymphocytes infiltrating orbital tissue and Graves orbitopathy activity, possibly enhancing understanding of the association between Graves orbitopathy immunologic features and clinical expression.

Abstract

Importance  Graves orbitopathy (GO) responds to immunosuppressive treatments when clinically active but poorly when inactive. In other autoimmune diseases, response has been ascribed to a reduction in lymphocytes infiltrating the target organ. It is not known whether active vs inactive GO differs in this regard, which would help in understanding the link between GO immunologic features and clinical behavior.

Objective  To investigate the association between orbital lymphocytic infiltrate and GO clinical features.

Design, Setting, and Participants  A cohort study aimed at assessing the extent and immunohistochemical phenotype of orbital lymphocytes and associating it with the ophthalmologic features of GO, especially its clinical activity score (CAS), was conducted at a tertiary referral center. Twenty consecutive patients with GO who underwent orbital decompression were included. The study was conducted from January 1 to May 31, 2017.

Exposures  Orbital tissue histology and immunohistochemistry testing as well as ophthalmologic evaluation.

Main Outcomes and Measures  Association between CAS and orbital lymphocytes, analyzed as total number of lymphocytes and main lymphoid subsets.

Results  The patient population included 8 men and 12 women, all of white race, with a mean (SD) age of 46 (13) years. With an established cutoff value of 300 lymphoid cells per tissue sample, lymphocytes above this value were found in orbital tissues of 9 of 20 patients (45%), often organized into distinct foci. The lymphocytes comprised a mixture of T (CD3-positive) and B (CD20-positive) cells, suggesting a mature, polyclonal autoimmune response. In a simple linear regression model, the total number of lymphocytes, as well as the number of CD3- and CD20-positive subsets, correlated with CAS (R = 0.63; 95% CI, 0.27-0.84; P = .003; R = 0.59; 95% CI, 0.20-0.82; P = .006; and R = 0.65; 95% CI, 0.30-0.85; P = .002, respectively). In a multiple linear regression model, lymphocytes maintained their effect on CAS when adjusted for 2 additional variables that were correlated with CAS—smoking and GO duration—highlighting even more the important role of orbital lymphocytes in affecting CAS (total number: R = 0.58; 95% CI, 0.18-0.82; P = .01; CD3-positive: R = 0.58; 95% CI, 0.17-0.82; P = .01; and CD20-positive: R = 0.59; 95% CI, 0.19-0.83; P = .01).

Conclusions and Relevance  This study shows a correlation between T and B lymphocytes infiltrating orbital tissues and the activity of GO, possibly enhancing our understanding of the association between GO immunologic features and clinical expression.

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