{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T23:04:33Z","timestamp":1780700673132,"version":"3.54.1"},"reference-count":39,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-15-00135"],"award-info":[{"award-number":["22-15-00135"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["2023-571-05\/2023"],"award-info":[{"award-number":["2023-571-05\/2023"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["22-15-00135"],"award-info":[{"award-number":["22-15-00135"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["2023-571-05\/2023"],"award-info":[{"award-number":["2023-571-05\/2023"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation for Scientific and Technological Development of Yugra","award":["22-15-00135"],"award-info":[{"award-number":["22-15-00135"]}]},{"name":"Foundation for Scientific and Technological Development of Yugra","award":["075-15-2019-1660"],"award-info":[{"award-number":["075-15-2019-1660"]}]},{"name":"Foundation for Scientific and Technological Development of Yugra","award":["2023-571-05\/2023"],"award-info":[{"award-number":["2023-571-05\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: The aim of this study was to evaluate the avidity of thyroid autoantibodies (Abs) in sera of patients with autoimmune thyroid disease (AITD) and thyroid autoantibody carriers without diagnosed AITD. Methods: A hydrogel microarray-based multiplex assay with the chaotrope destruction stage was developed to measure the avidity of thyroid disease-associated autoantibodies, including those targeting thyroperoxidase (TPO), thyroglobulin (Tg), and other minor antigens. Results: Evaluation of the assay in three independent cohorts of patients, totaling 266 individuals with and without AITD, demonstrated the heterogeneous avidity of autoantibodies to thyroid proteins. For the confirmation study, the median avidity index (AI) for AbTg was 29.9% in healthy autoantibody carriers, 52.6% for AITD patients, and 92.7% for type 1 diabetes (T1D) thyroid autoantibody carriers. The median AI for AbTPO was 39.9% in healthy carriers, 73.4% in AITD patients, 83.2% in T1D thyroid autoantibody carriers, and 98.5% in AITD patients with thyroid neoplasm. In patients with Hashimoto\u2019s thyroiditis and known disease duration, changes in the avidity maturation of AbTPO over time were demonstrated. Conclusions: Longitudinal studies of TPO- and\/or Tg-positive healthy individuals (with an interval of 1\u20132 years between visits) are needed to evaluate the maturation of autoantibody avidity during the asymptomatic phase and to assess the potential of autoantibody avidity as a prognostic marker for disease development.<\/jats:p>","DOI":"10.3390\/diagnostics15030341","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T09:16:26Z","timestamp":1738314986000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Microarray-Based Avidity Assay for Assessment of Thyroid Autoantibodies"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3091-8245","authenticated-orcid":false,"given":"Elena","family":"Savvateeva","sequence":"first","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Sokolova","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8771-8300","authenticated-orcid":false,"given":"Marina","family":"Yukina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Ministry of Health of Russia, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6876-3336","authenticated-orcid":false,"given":"Nurana","family":"Nuralieva","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Ministry of Health of Russia, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-1785","authenticated-orcid":false,"given":"Elena","family":"Kulagina","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0120-4163","authenticated-orcid":false,"given":"Maxim","family":"Donnikov","sequence":"additional","affiliation":[{"name":"Department of Children\u2019s Diseases, Medical Institute of Surgut State University, 628400 Surgut, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyudmila","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Department of Children\u2019s Diseases, Medical Institute of Surgut State University, 628400 Surgut, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kazakova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Ministry of Health of Russia, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Troshina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Ministry of Health of Russia, 117292 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-318X","authenticated-orcid":false,"given":"Dmitry","family":"Gryadunov","sequence":"additional","affiliation":[{"name":"Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1007\/s40618-020-01477-1","article-title":"An update on the pathogenesis of Hashimoto\u2019s thyroiditis","volume":"44","author":"Weetman","year":"2021","journal-title":"J. Endocrinol. Investig."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1136\/jcp-2022-208290","article-title":"Thyroid autoantibodies","volume":"76","author":"Dwivedi","year":"2023","journal-title":"J. Clin. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1093\/jalm\/jfab128","article-title":"Mistaken Identity: The Role of Autoantibodies in Endocrine Disease","volume":"7","author":"Nelson","year":"2022","journal-title":"J. Appl. Lab. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e24124","DOI":"10.1002\/jcla.24124","article-title":"High prevalence of thyroid hormone autoantibody and low rate of thyroid hormone detection interference","volume":"36","author":"Ni","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Vargas-Uricoechea, H., Nogueira, J.P., Pinz\u00f3n-Fern\u00e1ndez, M.V., and Schwarzstein, D. (2023). The usefulness of thyroid antibodies in the diagnostic approach to autoimmune thyroid disease. Antibodies, 12.","DOI":"10.20944\/preprints202306.1623.v1"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1055\/s-2007-960498","article-title":"Increased Serum Anti-Carbonic Anhydrase II Antibodies in Patients with Graves\u2019 Disease","volume":"115","author":"Alver","year":"2007","journal-title":"Exp. Clin. Endocrinol. Diabetes"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ruan, Y., Heng, X., Yang, L., He, W., Li, L., Wang, Z., Huang, S., Chen, Q., and Han, Z. (2024). Relationship between autoimmune thyroid antibodies and anti-nuclear antibodies in general patients. Front. Endocrinol., 15.","DOI":"10.3389\/fendo.2024.1368088"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"153098","DOI":"10.1016\/j.prp.2020.153098","article-title":"Thyroid cancer and thyroid autoimmune disease: A review of molecular aspects and clinical outcomes","volume":"216","author":"Armani","year":"2020","journal-title":"Pathol. Res. Pract."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"E1524","DOI":"10.1210\/jc.2012-4258","article-title":"Aberrant Overexpression of Pyruvate Kinase m2 is associated with aggressive tumor features and the BRAF mutation in papillary thyroid cancer","volume":"98","author":"Feng","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Montero-Calle, A., Garranzo-Asensio, M., Moreno-Casbas, M.T., Campuzano, S., and Barderas, R. (2024). Autoantibodies in cancer: A systematic review of their clinical role in the most prevalent cancers. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1455602"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.beem.2004.11.003","article-title":"Thyroid peroxidase autoantibodies in euthyroid subjects","volume":"19","author":"Prummel","year":"2005","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.beem.2013.07.003","article-title":"Thyroglobulin antibody (TgAb) methods\u2014Strengths, pitfalls and clinical utility for monitoring TgAb-positive patients with differentiated thyroid cancer","volume":"27","author":"Spencer","year":"2013","journal-title":"Best Pract. Res. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Fr\u00f6hlich, E., and Wahl, R. (2017). Thyroid Autoimmunity: Role of Anti-thyroid Antibodies in Thyroid and Extra-Thyroidal Diseases. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00521"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12026-013-8419-6","article-title":"Autoantibodies in the grocery shop: Does quantity matter?","volume":"56","author":"Damoiseaux","year":"2013","journal-title":"Immunol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1515\/cclm-2018-0037","article-title":"Harmonization in autoimmune thyroid disease diagnostics","volume":"56","author":"Tozzoli","year":"2018","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.bj.2020.10.009","article-title":"Modified ELISA for antibody avidity evaluation: The need for standardization","volume":"44","author":"Correa","year":"2021","journal-title":"Biomed. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/cea.14448","article-title":"Easy assessment of the avidity of polyclonal allergen-specific serum antibodies","volume":"54","author":"Strobl","year":"2024","journal-title":"Clin. Exp. Allergy"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Li, K., Dodds, M., Spreng, R.L., Abraha, M., Huntwork, R.H.C., Dahora, L.C., Nyanhete, T., Dutta, S., Wille-Reece, U., and Jongert, E. (2023). A tool for evaluating heterogeneity in avidity of polyclonal antibodies. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1049673"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1586\/14760584.2016.1128831","article-title":"How to assess the binding strength of antibodies elicited by vaccination against HIV and other viruses","volume":"15","author":"Klasse","year":"2016","journal-title":"Expert Rev. Vaccines"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/s41573-022-00501-8","article-title":"Avidity in antibody effector functions and biotherapeutic drug design","volume":"21","author":"Oostindie","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1177\/0961203319877243","article-title":"Clinical evaluation of total and high-avidity anti-dsDNA antibody assays for the diagnosis of systemic lupus erythematosus","volume":"28","author":"Yuan","year":"2019","journal-title":"Lupus"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1007\/s10067-020-05040-4","article-title":"Assessment of a high-avidity IgG ANAs for the diagnosis and activity prediction of systemic lupus erythematosus","volume":"39","author":"Zeng","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.5114\/ceji.2020.97901","article-title":"Avidity of anti-phospholipid antibodies in relation to their levels","volume":"45","author":"Malbohan","year":"2020","journal-title":"Cent. Eur. J. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1136\/ard-2023-224303","article-title":"Low avidity observed for anti-citrullinated peptide antibody is not a general phenomenon for autoantibodies","volume":"82","author":"Yamada","year":"2023","journal-title":"Ann. Rheum. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/j.jaut.2004.12.001","article-title":"Absence of avidity maturation of autoantibodies to the protein tyrosine phosphatase-like IA-2 molecule and glutamic acid decarboxylase (GAD65) during progression to type 1 diabetes","volume":"24","author":"Westerlund","year":"2005","journal-title":"J. Autoimmun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/j.1365-2249.2007.03336.x","article-title":"Affinity maturation of immunoglobulin A anti-tissue transglutaminase autoantibodies during development of coeliac disease","volume":"148","author":"Westerlund","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1111\/cei.12302","article-title":"Serum autoantibodies directed against transglutaminase-2 have a low avidity compared with alloantibodies against gliadin in coeliac disease","volume":"177","author":"Gelderman","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1159\/000069069","article-title":"Determination of IgG Subclasses and Avidity of Antithyroid Peroxidase Antibodies in Patients with Subclinical Hypothyroidism\u2014A Comparison with Patients with Overt Hypothyroidism","volume":"59","author":"Silva","year":"2003","journal-title":"Horm. Res. Paediatr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1365-2249.2010.04155.x","article-title":"Avidity of thyroglobulin antibody in sera from patients with Hashimoto\u2019s thyroiditis with different thyroid functional status","volume":"161","author":"Zhang","year":"2010","journal-title":"Clin. Exp. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.32607\/2075-8251-2018-10-2-48-5710.32607\/20758251-2018-10-4-4-18","article-title":"The EIMB Hydrogel Microarray Technology: Thirty Years Later","volume":"10","author":"Gryadunov","year":"2018","journal-title":"Acta Naturae"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Savvateeva, E.N., Yukina, M.Y., Nuralieva, N.F., Filippova, M.A., Gryadunov, D.A., and Troshina, E.A. (2021). Multiplex Autoantibody Detection in Patients with Autoimmune Polyglandular Syndromes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22115502"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Lysov, Y., Barsky, V., Urasov, D., Urasov, R., Cherepanov, A., Mamaev, D., Yegorov, Y., Chudinov, A., Surzhikov, S., and Rubina, A. (2017). Microarray analyzer based on wide field fluorescent microscopy with laser illumination and a device for speckle suppression. Biomed. Opt. Express, 8.","DOI":"10.1364\/BOE.8.004798"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jim.2017.04.004","article-title":"Description of a novel multiplex avidity assay for evaluating HPV antibodies","volume":"447","author":"Brady","year":"2017","journal-title":"J. Immunol. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ssewanyana, I., Rek, J., Rodriguez, I., Wu, L., Arinaitwe, E., Nankabirwa, J.I., Beeson, J.G., Mayanja-kizza, H., Rosenthal, P.J., and Dorsey, G. (2021). Impact of a Rapid Decline in Malaria Transmission on Antimalarial IgG Subclasses and Avidity. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.576663"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s42977-020-00061-1","article-title":"Why current quantitative serology is not quantitative and how systems immunology could provide solutions","volume":"72","author":"Prechl","year":"2021","journal-title":"Biol. Futur."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1177\/0961203312440057","article-title":"Avidity of anti-\u03b22-glycoprotein I antibodies in patients with antiphospholipid syndrome","volume":"21","author":"Kveder","year":"2012","journal-title":"Lupus"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.clinbiochem.2020.05.019","article-title":"Precision of autoantibody assays in clinical diagnostic laboratories: What is the reality?","volume":"83","author":"Senant","year":"2020","journal-title":"Clin. Biochem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"161","DOI":"10.2337\/diab.43.1.161","article-title":"GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes","volume":"43","author":"Bjork","year":"1994","journal-title":"Diabetes"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1002\/art.33489","article-title":"Avidity maturation of anti-citrullinated protein antibodies in rheumatoid arthritis","volume":"64","author":"Suwannalai","year":"2012","journal-title":"Arthritis Rheum."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/3\/341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:24:57Z","timestamp":1760027097000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/3\/341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,31]]},"references-count":39,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["diagnostics15030341"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15030341","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,31]]}}}