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. 2018 Jun 1;136(6):613-619.
doi: 10.1001/jamaophthalmol.2018.0806.

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

Giovanna Rotondo Dottore  1 , Liborio Torregrossa  2 , Patrizio Caturegli  3 , Ilaria Ionni  1 , Angela Sframeli  4 , Elena Sabini  1 , Francesca Menconi  1 , Paolo Piaggi  5 , Stefano Sellari-Franceschini  6 , Marco Nardi  4 , Francesco Latrofa  1 , Paolo Vitti  1 , Claudio Marcocci  7 , Fulvio Basolo  2 , Michele Marinò  1
Affiliations

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

Giovanna Rotondo Dottore et al. JAMA Ophthalmol. .

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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Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1.
Figure 1.. Immunohistochemical Staining for CD3 and CD20 in Orbital Tissues
CD3 and CD20 staining in orbital tissues of 2 representative patients with Graves orbitopathy with scarce (A) and marked (B) infiltrate (hematoxylin-eosin, original magnification ×112).
Figure 2.
Figure 2.. Orbital Lymphocytes and Clinical Activity Score (CAS) in White Patients (8 Men, 12 Women; Mean [SD] Age, 46 [13] Years) With Graves Orbitopathy
A, Correlation between total lymphocytes and CAS (P = .003). B, Correlation between CD3-positive lymphocytes and CAS (P = .006). C, Correlation between CD20-positive lymphocytes and CAS (P = .002). D, CAS (median and interquartile range) according to the presence a relevant (>300 cells in 4 fields) lymphocytic infiltrate.
Figure 3.
Figure 3.. Individual Levels of Serum Anti–Thyrotropin Receptor Antibodies (TRAbs) in White Patients (8 Men, 12 Women; Mean [SD] Age, 46 [13] Years)
Levels of serum TRAbs according to presence of a relevant (>300 cells in 4 fields) orbital lymphocytic infiltrate.
See this image and copyright information in PMC

Comment in

References

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