ETA2023 Poster Presentations Basic Thyroid Gland, Iodine & Autoimmunity Basic (9 abstracts)
Analysis of T- and B- lymphocytic infiltrate of target tissues in patients with graves’ disease and orbitopathy
Sara Maioli 1 , Mario Salvi 2 , Giorgia Moschetti 3 , Mariacristina Crosti 3 , Erica Crivicich 4 , Francesco Di Marco 4 , Giada Rossi 4 , Nicola Currò 2 , Alessia Dolci 5 , Maura Arosio 2 , Giovanna Mantovani 6 , Colin Dayan 7 , Jens Geginat 6 & Ilaria Muller 6
1University of Milan, Department of Clinical Sciences and Community Health, Milan, Italy; 2Graves Orbitopathy Center, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy; 3National Institute of Molecular Genetics, Milan, Italy; 4University of Milan, Italy; 5Endocrinology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Milan, Italy; 6Department of Clinical Sciences and Community Health, University of Milan, Italy; 7Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK
Objectives: In Graves’ disease (GD) and Graves’ orbitopathy (GO) self-reactive lymphocytes escape immune tolerance, although the underlying mechanisms are not fully understood. We aimed to characterize the immune signatures of target tissue-resident lymphocytes in relation to GD and GO.
Methods: Lymphocytes were derived from blood and ultrasound-guided-fine-needle aspiration (US-FNA) of thyroid and neck lymph nodes (LNs) of the following patients: 13 GD (newly diagnosed or relapsed), 7 GD with active GO (GO-A; ongoing orbital inflammation), 14 GD with inactive GO (GO-I; absent orbital inflammation), 6 Hashimoto’s thyroiditis (HT), 15 non-autoimmune multinodular goiter (MNG) and 3 healthy donors (HD). Lymphocytes were also isolated from orbital tissues of 5 patients with Dysthyroid Optic Neuropathy (DON) and 6 GO-I after orbital decompression. Lymphocytes were immunophenotyped by flow cytometry (FACSymphonyTM cytometer) with a 21 surface/intracellular staining panel. Intracellular cytokines were detected following stimulation with PMA and ionomycin.
Results: In LNs, thyroid and PBMCs patients, GD, GO and HT groups show increased T regulatory cell (Treg) numbers when compared with HD. However, in PBMCs of patients with GO-A, Tregs show a lower production of IL-10. Patients with GD and GO present in both thyroid and LNs an increased number of T follicular helper cells (Tfh), as well as a reduction of the Germinal Center-B/Germinal Center-Tfh ratio. B and T lymphocytic infiltrates were found in all analyzed orbital tissues. Our preliminary results show that in DON patients the number of intra-orbital CD19+ B cells is increased compared to GO-I patients.
Conclusions: By neck LN and thyroid sampling with US-FNA we were able to immunophenotype patients with thyroid autoimmune disease. By also studying lymphocytes directly isolated from the orbital tissue, we were able to detect more specific tissue-resident lymphocytes. The increase in Treg cells in patients with thyroid autoimmunity could indicate an attempt by these cells to suppress the altered immune response, or a compensatory consequence of their dysfunction, as observed in GO-A patients. Furthermore, thyroid autoimmunity, especially GD and GO, appears to be characterized by an increase of Tfh cells. Intra-orbital B and T infiltrate characterize GO and may correlate with disease severity, as shown in patients with DON. The extension of this analysis to a larger number of patients will further validate our findings and allow identification of specific immune signatures of GD and GO.
Volume 92
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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