ETA2024 Poster Presentations Autoimmunity (8 abstracts)
Specific patterns of orbital-resident B and T lymphocytes are related to different clinical presentations of thyroid eye disease
Sara Maioli 1 , Mario Salvi 2 , Mirco Armenti 3 , Erica Crivicich 4 , Nicola Currò 5 , Claudio Guastella 6 , Beatrice Dazzi 4 , Giorgia Moschetti 7 , Mariacristina Crosti 7 , Giovanna Mantovani 8 , Jens Geginat 9 & Ilaria Muller 10
1University of Milan, Italy, Department of Clinical Sciences and Community Health, Milan, Italy; 2Graves Orbitopathy Centre, Endocrine, Fondazione Irccs Ca’ Granda, University of Milan, Milan, Italy; 3Graves Orbitopathy Center, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, University of Milan, Endocrinology, Milan, Italy; 4University of Milan, Italy, Department of Clinical Sciences and Community Health; 5Ophthalmology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Graves Orbitopathy Center, Endocrinology Unit, Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, Italy; 6Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico, Graves Orbitopathy Center, Endocrinology Unit, Fondazione Irccs Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; 7National Institute of Molecular Genetics (Ingm), Milan, Italy; 8University of Milan, Fondazione Irccs Ca’ Granda, Clinical Sciences and Community Health, Milano, Italy; 9National Institute of Molecular Genetics (Ingm), Milan, Italy, Italy; 10University of Milan, Clinical Sciences and Community Health; Endocrinology; Graves’ Orbitopathy Centre, Clinical Sciences and Community Health, Milan, Italy
Objectives: Thyroid Eye Disease (TED) is an autoimmune process affecting orbital tissues, characterized by an active florid inflammation phase, followed by an inactive fibrotic phase. Treatments include immunosuppressants, usually glucocorticoids (GC), administered in the active phase, and rehabilitative orbital surgery in the inactive phase. The most severe TED cases are characterized by dysthyroid optic neuropathy (DON), requiring emergency GC and surgical treatments. We aimed to study if specific phenotypes of orbital-infiltrating lymphocytes are related to different clinical TED manifestations.
Methods: Lymphocytes were isolated from peripheral blood and orbital tissues of 19 patients undergoing orbital decompression for inactive TED (TED-I), and 11 patients for DON. Among the 19 TED-I patients, 11 had never been treated with GC (TED-I-Naïve), whereas 8 TED-I patients received GC to inactivate TED a median time of 3 years before surgery (TED-I-postGC). All DON patients also had signs of active orbital inflammation and were treated with GC before orbital decompression (mean 3 months). Isolated lymphocytes were immunophenotyped by flow cytometry with a 21 surface/intracellular staining panel.
Results: DON and TED-I-post-GC patients showed marked orbital T and B cell infiltration, calculated as the number of cells per gram of tissue, compared to TED-I-Naïve patients. DON patients showed an increased frequency of orbital CD19+ B, follicular T helper (Tfh), and germinal center B and T cells, compared to TED-I-Naïve patients. The degree of orbital infiltrating B and Tfh cells negatively correlated with the duration of TED disease in a simple linear regression model (P = 0.02 and P = 0.03, respectively).
Conclusions: Our findings suggest that the degree of orbital B and T lymphocyte infiltration correlates with TED activity and duration, and the presence of B and T lymphocytes involved in germinal responses seem predominant in the most severe and active cases of TED complicated with DON. Interestingly, the orbital infiltration of TED-I patients who were previously treated with GC (TED-I-postGC) was similar to that of DON, and markedly higher compared with TED-I patients who never received GC (TED-I-Naïve). While lymphocytic infiltrates in more active and severe TED cases may persist in the orbit independently of GC treatment, they appear to be less evident in milder and spontaneously self-limiting forms of TED. The observed negative correlation between the degree of orbital B and T cell infiltration and TED duration may explain why immunosuppressive treatments have the highest efficacy if administered in the early phases of disease.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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