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Using computational modeling, epitopes of NIS were tested for their ability to trigger immune responses relevant to SS in Hashimoto’s thyroiditis (HT) patients with shared genetic predisposition. TepiTool, ABCpred, and DiscoTope 2.0 predicted T- and B-cell epitopes from NIS, TPO, and Ro60. A total of 376 linear T-cell epitopes, 64 linear B-cell epitopes, and 68 conformational B-cell epitopes were identified. Compared with TPO, NIS T-cell epitopes showed lower HLA binding affinity (p \u003C 0.0001), with no difference versus Ro60. Conformational NIS B-cell epitopes were predicted to be more immunogenic than Ro60 (p = 0.04), while no significant difference was found versus TPO. 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It is also expressed in salivary glands, which are key targets of autoreactive cells in Sjögren’s syndrome, making it relevant to both conditions.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How were T-cell and B-cell epitopes predicted in this study?",{"text":118,"@type":114},"The study used computational servers (TepiTool 2016, ABCpred 2006, and DiscoTope 2.0) with FASTA sequences and 3D structures for NIS and reference antigens TPO and Ro60.",{"name":120,"@type":111,"acceptedAnswer":121},"What key immunogenicity differences did the authors find for NIS epitopes?",{"text":122,"@type":114},"Compared with TPO, NIS T-cell epitopes showed significantly lower HLA binding affinity (p \u003C 0.0001). 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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.  \n1 Rheumatology Unit, Department of Clinical and Experimental Medicine, University Hospital “G. Martino”, University of Messina, 98124 Messina, Italy  \n2 Medicine and Surgery Bachelor Degree Course, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University Hospital “G. Martino”, University of Messina,  \n98124 Messina, Italy; [gabriele.2003@outlook.it](gabriele.2003@outlook.it)  \n3 Endocrinology Unit, Department of Human Pathology of Adulthood and Childhood DETEV “G. Barresi”, University Hospital “G. Martino”, University of Messina, 98124 Messina, Italy; rmruggeri@unime.it (R.M.R.); [cannavos@unime.it](cannavos@unime.it) (S.C.)  \n4 Ophthalmology Clinic, Department of Biomedical Sciences, University Hospital “G. Martino”, University of Messina, 98124 Messina, Italy; [elisapostorino@virgilio.it](elisapostorino@virgilio.it) (E.P.); [paragona@unime.it](paragona@unime.it) (P.A.)  \n* Correspondence: [rtalotta@unime.it](rtalotta@unime.it)[ ](rtalotta@unime.it)† These authors contributed equally to this work.  \nAbstract  \nThe 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 Sjögren’s 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’s 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 \u003C 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.  \nKeywords: B-cell epitopes; computational analysis; Hashimoto’s thyroiditis; NIS; prediction models; Sjögren’s syndrome; T-cell epitopes  \n1. Introduction  \nSjögren’s syndrome (SS) is a systemic autoimmune disease mainly affecting exocrine glands, particularly salivary and lacrimal glands, causing xerostomia and xerophthalmia  \nin most patients [1,2] . Other symptoms include dysphagia, oral burning, gland swelling, and eye complications. Dysfunction of other exocrine glands can cause vaginal dryness, hoarseness, cough, pancreatitis, and gastritis [1] . Extraglandular involvement may","cbCaitu9t9JhRcmC","https://ap.wps.com/l/cbCaitu9t9JhRcmC","pdf",1771775,27,"English","# Abstract\n# Keywords\n# Introduction\n## Sjögren’s syndrome overview\n## Prevalence and risk factors\n## Links between SS and Hashimoto’s thyroiditis","[{\"question\":\"What is NIS and why is it relevant to autoimmune thyroiditis and Sjögren’s syndrome?\",\"answer\":\"NIS is a protein essential for iodine uptake in thyroid function. It is also expressed in salivary glands, which are key targets of autoreactive cells in Sjögren’s syndrome, making it relevant to both conditions.\"},{\"question\":\"How were T-cell and B-cell epitopes predicted in this study?\",\"answer\":\"The study used computational servers (TepiTool 2016, ABCpred 2006, and DiscoTope 2.0) with FASTA sequences and 3D structures for NIS and reference antigens TPO and Ro60.\"},{\"question\":\"What key immunogenicity differences did the authors find for NIS epitopes?\",\"answer\":\"Compared with TPO, NIS T-cell epitopes showed significantly lower HLA binding affinity (p \\u003c 0.0001). For B-cell epitopes, conformational NIS epitopes were predicted to have higher immunogenicity than Ro60 (p = 0.04), while linear B-cell epitopes across NIS, TPO, and Ro60 showed similar binding affinity.\"}]","Predicted T-Cell and B-Cell Epitopes of NIS: Where Do Sjögren’s Syndrome and Hashimoto’s Thyroiditis Converge? | PDF",1790769738,68]