{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:00:51Z","timestamp":1762077651006,"version":"build-2065373602"},"reference-count":41,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Fund, Bulgaria","award":["KP-06-H33\/15\/2019"],"award-info":[{"award-number":["KP-06-H33\/15\/2019"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hashimoto\u2019s thyroiditis is one of the most common endocrine disorders, affecting up to 20% of the adult population. No treatment or prevention exists except hormonal substitution for hypothyroidism. We hypothesize that it may be possible to selectively suppress anti-thyroglobulin (Tg) IgG antibody-producing B lymphocytes from HT patients by a chimeric protein molecule containing a monoclonal antibody specific for the human inhibitory receptor CR1, coupled to peptide epitopes derived from Tg protein. We expect that this treatment will down-regulate B-cell autoreactivity by delivering a strong inhibitory signal. Three peptides\u2014two epitope-predicted ones derived from Tg and another irrelevant peptide\u2014were synthesized and then coupled with monoclonal anti-human CR1 antibody to construct three chimeric molecules. The binding to CD35 on human B cells and the effects of the chimeric constructs on PBMC and TMC from patients with HT were tested using flow cytometry, ELISpot assay, and immunoenzyme methods. We found that after the chemical conjugation, all chimeras retained their receptor-binding capacity, and the Tg epitopes could be recognized by anti-Tg autoantibodies in the patients\u2019 sera. This treatment downregulated B-cell autoreactivity and cell proliferation, inhibited Tg-specific B-cell differentiation to plasmablasts and promoted apoptosis to the targeted cells. The treatment of PBMCs from HT patients with Tg-epitope-carrying chimeric molecules affects the activity of Tg-specific autoreactive B lymphocytes, delivering to them a strong suppressive signal.<\/jats:p>","DOI":"10.3390\/ijms232315083","type":"journal-article","created":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T04:28:57Z","timestamp":1669868937000},"page":"15083","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Selective Silencing of Disease-Associated B Lymphocytes from Hashimoto\u2019s Thyroiditis Patients by Chimeric Protein Molecules"],"prefix":"10.3390","volume":"23","author":[{"given":"Nikola Ralchev","family":"Ralchev","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandar Mishel","family":"Markovski","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inna Angelova","family":"Yankova","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iliyan Konstantinov","family":"Manoylov","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-1768","authenticated-orcid":false,"given":"Irini Atanas","family":"Doytchinova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8582-9296","authenticated-orcid":false,"given":"Nikolina Mihaylova","family":"Mihaylova","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9203-4149","authenticated-orcid":false,"given":"Alexander Dimitrov","family":"Shinkov","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Medical Faculty, Medical University of Sofia, 1431 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey Ivanov","family":"Tchorbanov","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Immunology, Institute of Microbiology, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria"},{"name":"National Institute of Immunology, 1517 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/BF03401283","article-title":"An overview of the pathogenesis of thyroid autoimmunity","volume":"12","author":"Cogni","year":"2013","journal-title":"Hormones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3389\/fimmu.2019.00344","article-title":"Molecular Insights Into the Relationship Between Autoimmune Thyroid Diseases and Breast Cancer: A Critical Perspective on Autoimmunity and ER Stress","volume":"10","author":"Rahman","year":"2019","journal-title":"Front. 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