{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:06:16Z","timestamp":1773464776369,"version":"3.50.1"},"reference-count":127,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"institutional research funds"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The sodium iodide symporter (NIS) is a key protein in thyroid function responsible for iodine uptake, and it may be involved in the pathogenesis of autoimmune thyroiditis. However, it is also expressed in the salivary glands, the primary target of autoreactive cells in Sj\u00f6gren\u2019s syndrome (SS). Given the common link between the two diseases, we computationally investigated whether the epitopes of NIS can trigger an immune response leading to SS in Hashimoto\u2019s thyroiditis (HT) patients genetically predisposed to both diseases. The TepiTool 2016, ABCpred 2006, and DiscoTope 2.0 servers were used to predict T-cell and B-cell epitopes by inputting the FASTA sequences and 3D structures of NIS, thyroid peroxidase (TPO) and Ro60 Y RNA-binding protein (Ro60), which served as reference antigens for HT and SS, respectively. T-cell epitopes were selected based on their binding to a panel of human leukocyte antigen (HLA) alleles associated with both SS and HT. We identified a total of 376 linear T-cell epitopes, 64 linear B-cell epitopes and 68 conformational B-cell epitopes of NIS. Compared to TPO, NIS T-cell epitopes showed significantly lower affinity for HLA alleles (p &lt; 0.0001), while no significant difference was found compared to Ro60. While linear B-cell epitopes of NIS, TPO, and Ro60 showed similar binding affinity, conformational epitopes of NIS were predicted to have higher immunogenicity than Ro60 (p = 0.04), while no significant difference was found compared to TPO. These pivotal findings, discovered by the methods of computer modeling, suggest that NIS can potentially activate T cells and B cells in patients with genetic predisposition to SS and HT and need to be confirmed by further laboratory studies.<\/jats:p>","DOI":"10.3390\/ijms27010200","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Predicted T-Cell and B-Cell Epitopes of NIS: Where Do Sj\u00f6gren\u2019s Syndrome and Hashimoto\u2019s Thyroiditis Converge?"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8426-1395","authenticated-orcid":false,"given":"Rossella","family":"Talotta","sequence":"first","affiliation":[{"name":"Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2559-2572","authenticated-orcid":false,"given":"Gabriele","family":"Cammaroto","sequence":"additional","affiliation":[{"name":"Medicine and Surgery Bachelor Degree Course, Department of Human Pathology of Adulthood and Childhood DETEV \u201cG. Barresi\u201d, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-684X","authenticated-orcid":false,"given":"Rosaria Maddalena","family":"Ruggeri","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV \u201cG. Barresi\u201d, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisa","family":"Postorino","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8779-7283","authenticated-orcid":false,"given":"Salvatore","family":"Cannav\u00f2","sequence":"additional","affiliation":[{"name":"Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV \u201cG. Barresi\u201d, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-9799","authenticated-orcid":false,"given":"Pasquale","family":"Aragona","sequence":"additional","affiliation":[{"name":"Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital \u201cG. Martino\u201d, University of Messina, 98124 Messina, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s10238-021-00728-6","article-title":"Sj\u00f6gren\u2019s Syndrome: A Systemic Autoimmune Disease","volume":"22","author":"Negrini","year":"2022","journal-title":"Clin. Exp. 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