ETA2022 Oral Presentations Oral Session 11: Young Investigators / Basic (6 abstracts)
Study of target tissue-resident immune cells in graves’ disease and orbitopathy (star-GO): preliminary findings with a novel extensive immunophenotyping panel
Sara Maioli 1 , Mario Salvi 2 , Giorgia Moschetti 3 , Mariacristina Crosti 3 , Erica Crivicich 4 , Francesco Di Marco 4 , Nicola Currò 5 , Alessia Dolci 6 , Maura Arosio 7 , Giovanna Mantovani 8 , Colin Dayan 9 , Jens Geginat 3 & Ilaria Muller 10
1Department of Clinical Sciences and Community Health, University of Milan, Italy; 2Graves Orbitopathy Centre, Endocrine, Fondazione Irccs Ca’ Granda, University of Milan, Milan, Italy; 3National Institute of Molecular Genetics, Milan, Italy; 4Graves Orbitopathy Centre, Endocrine; Fondazione Irccs Ca’ Granda, University of Milan, University of Milan, Milan, Italy; 5Ophthalmology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico, Italy; 6Endocrinology, Fondazione Irccs Cà Granda, Ospedale Maggiore Policlinico; 7Graves’ Orbitopathy Centre, Endocrinology Department, Fondazione Irccs Ca’ Granda, University of Milan, University of Milan, Clinical Sciences and Community Health, Milan, Italy, Milan, Italy; 8University of Milan, Fondazione Irccs Ca’ Granda, Clinical Sciences and Community Health, Milano, Italy; 9Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, United Kingdom; 10University of Milan; Fondazione Irccs Ca’ Granda Policlinico Hospital of Milan, Clinical Sciences and Community Health; Endocrinology; Graves’ Orbitopathy Centre, Milan, Italy
Background and Aims: Graves’ disease (GD) and orbitopathy (GO) are characterised by the presence of pathological anti-thyrotropin receptor antibodies. In thyroid autoimmunity, especially GD and GO, a dysregulation of several T cell subpopulations has been proposed, especially T regulatory (Treg) and T helper 17 (Th17) cells, determining (auto)immunity inhibition and enhancement, respectively. T follicular cells (Tf) within germinal centres (GC: aggregates of lymphocytes within tissues) are also crucial, since supporting the maturation of GC-B cells that will later generate antibodies. The STAR-GO project aims to characterise immune signatures of GD/GO in relation with disease activity by analising tissue-resident lymphocytes, more specific than those blood-derived.
Materials and Methods: Lymphocytes were derived from blood sampling and ultrasound-guided-fine-needle aspiration (US-FNA) of thyroid and neck lymph nodes (LNs) performed in the following patients: 6 GD early-onset (GD-E; newly diagnosed or recently relapsed) 2 active GO (GO-A; ongoing orbital inflammation), 3 inactive GO (GO-I; absent orbital inflammation) and 2 Hashimoto’s thyroiditis (HT). Lymphocytes were immunophenotyped by flow cytometry (BD FASCSymphony0) with a 21 surface/intracellular staining panel.
Results: In the LNs analysis, B cells were more abundant in GD and GO, while T cells in HT. Among T cells, both GD and GO had increased Th17 cells compared with HT, while both GO-A and GO-I showed a peculiar increase of Tf-helper cells (Tfh). GC-B cells were highly abundant in GD-E, GO-A and especially in HT, while very low in GO-I; as a consequence GO-I patients had the lowest GC-B/GC-Tfh ratio (0.1), compared with GD-E (0.62), GO-A (0.70) and HT (0.94). The immunophenotyping of PBMC and thyroid did not show particular differences among the patient groups.
Conclusions: Our preliminary results show that:.
- Neck LN sampling with US-FNA is an effective tool for the immunophenotyping of patients with thyroid autoimmunity, more specific and informative than blood;.
- GD and GO patients showed increased numbers of B cells, while HT patients of T cells, likely reflecting the different disease pathogenesis (predominantly humoral vs cell-mediated);.
- Increased Th17 cells identify both GD and GO patients, while Tfh cells seem particularly important for GO;.
- As expected, GO during its inactive phase (GO-I) showed a low GC activity.
We are currently increasing the number of subjects to verify our findings and further distinguish the different phases of GD/GO disease activity.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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