Analysis of T- and B- lymphocytic infiltrate of target tissues in patients with graves

Sara Maioli; Mario Salvi; Giorgia Moschetti; Mariacristina Crosti; Erica Crivicich; Marco Francesco Di; Giada Rossi; Nicola Curro; Alessia Dolci; Maura Arosio; Giovanna Mantovani; Colin Dayan; Jens Geginat; Ilaria Muller

doi:10.1530/endoabs.92.PS1-10-09

PS1-10-09

Prev Next

Section Contents Cite

Endocrine Abstracts (2023) 92 PS1-10-09 | DOI: 10.1530/endoabs.92.PS1-10-09

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

Err

Author affiliations

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.