{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T04:43:10Z","timestamp":1766983390610,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"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":["IJMS"],"abstract":"<jats:p>This study investigated the IgA antibodies targeting bovine serum albumin (BSA) in 27 adult celiac disease (CD) patients adhering to a gluten-free diet (GFD), compared to 123 controls (including individuals with autoimmune disorders, those with gastrointestinal cancers, and healthy donors). Serum samples were evaluated using a multiplex assay based on a microarray comprising 66 immobilized antigens, including autoantigens associated with autoimmune diseases, different albumins, cytokines, and inflammatory markers. Elevated IgA-BSA levels were detected in 22% of CD patients versus 3.25% of controls. IgA-BSA did not cross-react with milk proteins like casein, \u03b2-lactoglobulin, and \u03b3-globulin, nor with autoantigens and human albumin, ruling out autoimmunity against self-proteins. The observed cross-reactivity with porcine albumin suggests that antibodies target epitopes shared by bovine and porcine albumin. Increased IgA-BSA levels may interfere with immunoassays performed using BSA as a stabilizer, necessitating protein-free buffers to avoid false results when testing CD patients. Elevated IgA-BSA levels may reflect ongoing gut barrier dysfunction in CD patients on a GFD, allowing dietary proteins like BSA to trigger immune responses. This study identifies a novel immune response in CD patients on a GFD, emphasizing the need for tailored diagnostic approaches (BSA-free assays) and further research into the clinical and dietary implications of IgA-BSA elevation.<\/jats:p>","DOI":"10.3390\/ijms26114988","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T10:24:45Z","timestamp":1747909485000},"page":"4988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IgA Antibodies to Bovine Serum Albumin in Adult Patients with Celiac Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3091-8245","authenticated-orcid":false,"given":"Elena","family":"Savvateeva","sequence":"first","affiliation":[{"name":"Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana","family":"Bykova","sequence":"additional","affiliation":[{"name":"The Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6954-1564","authenticated-orcid":false,"given":"Ivan","family":"Abramov","sequence":"additional","affiliation":[{"name":"The Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Polyakova","sequence":"additional","affiliation":[{"name":"The Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Bodunova","sequence":"additional","affiliation":[{"name":"The Loginov Moscow Clinical Scientific Center, 111123 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lyudmila","family":"Kovalenko","sequence":"additional","affiliation":[{"name":"Department of Children\u2019s Diseases, Medical Institute of Surgut State University, 628400 Surgut, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-1993","authenticated-orcid":false,"given":"Elena","family":"Mazurenko","sequence":"additional","affiliation":[{"name":"Research Institute of Internal and Preventive Medicine\u2014Branch of the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630089 Novosibirsk, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta","family":"Pavlova","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5381-1785","authenticated-orcid":false,"given":"Elena","family":"Kulagina","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ekaterina","family":"Troshina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre, Ministry of Health of Russia, 117292 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3183-318X","authenticated-orcid":false,"given":"Dmitry","family":"Gryadunov","sequence":"additional","affiliation":[{"name":"Engelhardt Institute of Molecular Biology (EIMB), Russian Academy of Sciences, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/nm0797-797","article-title":"Identification of tissue transglutaminase as the autoantigen of celiac disease","volume":"3","author":"Dieterich","year":"1997","journal-title":"Nat. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.cgh.2017.06.037","article-title":"Global Prevalence of Celiac Disease: Systematic Review and Meta-analysis","volume":"16","author":"Singh","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kvamme, J.M., S\u00f8rbye, S., Florholmen, J., and Halstensen, T.S. (2022). Population-based screening for celiac disease reveals that the majority of patients are undiagnosed and improve on a gluten-free diet. Sci. Rep., 12.","DOI":"10.1038\/s41598-022-16705-2"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Penny, H.A., Baggus, E.M.R., Rej, A., Snowden, J.A., and Sanders, D.S. (2020). Non-Responsive Coeliac Disease: A Comprehensive Review from the NHS England National Centre for Refractory Coeliac Disease. Nutrients, 12.","DOI":"10.3390\/nu12010216"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1038\/ajg.2010.10","article-title":"Mucosal Recovery and Mortality in Adults with Celiac Disease After Treatment with a Gluten-Free Diet","volume":"105","author":"Rahim","year":"2010","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","first-page":"511","article-title":"Zonulin and I-FABP are markers of enterocyte damage in celiac disease","volume":"94","author":"Bykova","year":"2022","journal-title":"Ter. Arkh."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1159\/000233819","article-title":"Humoral Immunity to Dietary Antigens in Healthy Adults","volume":"77","author":"Husby","year":"1985","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Cai, C., Shen, J., Zhao, D., Qiao, Y., Xu, A., Jin, S., Ran, Z., and Zheng, Q. (2014). Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with Inflammatory Bowel Diseases. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112154"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1016\/j.immuni.2022.11.004","article-title":"Allergenic food protein consumption is associated with systemic IgG antibody responses in non-allergic individuals","volume":"55","author":"Leviatan","year":"2022","journal-title":"Immunity"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1111\/imr.13369","article-title":"All roads lead to IgA: Mapping the many pathways of IgA induction in the gut","volume":"326","author":"Siniscalco","year":"2024","journal-title":"Immunol. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"102459","DOI":"10.1016\/j.autrev.2020.102459","article-title":"Interaction between food antigens and the immune system: Association with autoimmune disorders","volume":"19","author":"Vojdani","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1056\/NEJM199207303270502","article-title":"A Bovine Albumin Peptide as a Possible Trigger of Insulin-Dependent Diabetes Mellitus","volume":"327","author":"Karjalainen","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1111\/j.1651-2227.1995.tb13544.x","article-title":"IgA bovine serum albumin antibodies are increased in newly diagnosed patients with insulin-dependent diabetes mellitus, but the increase is not an independent risk factor for diabetes","volume":"84","author":"Saukkonen","year":"1995","journal-title":"Acta Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1006\/jaut.1998.0199","article-title":"Anti-BSA Antibodies do not Cross-react with the 69-kDa Islet Cell Autoantigen ICA69","volume":"11","author":"Atrazhev","year":"1998","journal-title":"J. Autoimmun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1016\/j.tjnut.2024.06.005","article-title":"High Concentrations of Immunoglobulin G Against Cow Milk Proteins and Frequency of Cow Milk Consumption Are Associated With the Development of Islet Autoimmunity and Type 1 Diabetes\u2014The Trial to Reduce Insulin-dependent Diabetes Mellitus (IDDM) in the Gen","volume":"154","author":"Cuthbertson","year":"2024","journal-title":"J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jim.2005.01.022","article-title":"IgG antibodies against bovine serum albumin in humans\u2014Their prevalence and response to exposure to bovine serum albumin","volume":"300","author":"Mogues","year":"2005","journal-title":"J. Immunol. Methods"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Grace, S.L., Mortimer, G.L., Kozhakhmetova, A., Leveret, J., Newton, R., Reimand, K., Shield, J.P.H., Uibo, R., Williams, A.J.K., and Gillespie, K.M. (2023). Increased levels of anti-BSA antibodies in children with Down syndrome. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1056925"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1056\/NEJMoa1013792","article-title":"Early-Childhood Membranous Nephropathy Due to Cationic Bovine Serum Albumin","volume":"364","author":"Debiec","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1136\/gut.11.8.635","article-title":"Immunoglobulins and dietary protein antibodies in childhood coeliac disease","volume":"11","author":"Kenrick","year":"1970","journal-title":"Gut"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/S0016-5085(76)80394-0","article-title":"Circulating antibodies to bovine albumin in ulcerative colitis and Crohn\u2019s disease. Characterization of the antibody response","volume":"70","author":"Falchuk","year":"1976","journal-title":"Gastroenterology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1159\/000234680","article-title":"ELISA Analysis of IgA Subclass Antibodies to Dietary Antigens","volume":"87","author":"Kemp","year":"1988","journal-title":"Int. Arch. Allergy Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1136\/gut.33.5.632","article-title":"Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease","volume":"33","author":"Hvatum","year":"1992","journal-title":"Gut"},{"key":"ref_23","first-page":"132","article-title":"Increased levels of bovine serum albumin antibodies in patients with type 1 diabetes and celiac disease-related antibodies","volume":"37","author":"Valeri","year":"2003","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1046\/j.1365-2249.2001.01451.x","article-title":"Differential binding of IgG and IgA antibodies to antigenic determinants of bovine serum albumin","volume":"123","author":"Hilger","year":"2001","journal-title":"Clin. Exp. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"133170","DOI":"10.1016\/j.foodchem.2022.133170","article-title":"Characterization and determination of bovine immunoglobulin G subtypes in milk and dairy products by UPLC-MS","volume":"390","author":"Zhang","year":"2022","journal-title":"Food Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qin, C., Li, Y., Zhang, Y., Liu, L., Wu, Z., and Weng, P. (2021). Insights into oat polyphenols constituent against advanced glycation end products mechanism by spectroscopy and molecular interaction. Food Biosci., 43.","DOI":"10.1016\/j.fbio.2021.101313"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10221","DOI":"10.1039\/D3FO02474A","article-title":"The binding mechanism of oat phenolic acid to whey protein and its inhibition mechanism against AGEs as revealed using spectroscopy, chromatography and molecular docking","volume":"13","author":"Dong","year":"2023","journal-title":"Food Funct."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1111\/j.1365-2249.2007.03298.x","article-title":"Mucosal reactivity to cow\u2019s milk protein in coeliac disease","volume":"147","author":"Venge","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1080\/09540100400003204","article-title":"IgA anti-gliadin antibody immunoreactivity to food proteins","volume":"15","author":"Berti","year":"2003","journal-title":"Food Agric. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/S1081-1206(10)62121-7","article-title":"Beef allergy in children with cow\u2019s milk allergy; cow\u2019s milk allergy in children with beef allergy","volume":"89","author":"Martelli","year":"2002","journal-title":"Ann. Allergy Asthma Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Nehring, J., Schirmbeck, L.A., Friebus-Kardash, J., Dubler, D., Huynh-Do, U., Chizzolini, C., Ribi, C., and Trendelenburg, M. (2018). Autoantibodies Against Albumin in Patients with Systemic Lupus Erythematosus. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02090"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jim.2010.09.009","article-title":"Anti-BSA antibodies are a major cause of non-specific binding in insulin autoantibody radiobinding assays","volume":"362","author":"Williams","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"ref_33","first-page":"316","article-title":"Bovine serum albumin antibodies as a disease marker for hepatitis E virus infection","volume":"2005","author":"Haroun","year":"2005","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3899\/jrheum.100690","article-title":"Beware of Antibodies to Dietary Proteins in \u201cAntigen-specific\u201d Immunoassays! Falsely Positive Anticytokine Antibody Tests Due to Reactivity with Bovine Serum Albumin in Rheumatoid Arthritis (The Swedish TIRA Project)","volume":"38","author":"Kastbom","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1002\/hep.32134","article-title":"Quantification of polyreactive immunoglobulin G facilitates the diagnosis of autoimmune hepatitis","volume":"75","author":"Taubert","year":"2022","journal-title":"Hepatology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100880","DOI":"10.1016\/j.xkme.2024.100880","article-title":"False-positive Serum Antiglomerular Basement Membrane Antibody due to Bovine Serum Albumin-containing Surgical Adhesive: A Case Report","volume":"6","author":"Yoshida","year":"2024","journal-title":"Kidney Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jim.2014.03.013","article-title":"Preventing intense false positive and negative reactions attributed to the principle of ELISA to re-investigate antibody studies in autoimmune diseases","volume":"407","author":"Terato","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jim.2019.01.004","article-title":"Reducing the risk of misdiagnosis of indirect ELISA by normalizing serum-specific background noise: The example of detecting anti-FGFR3 autoantibodies","volume":"466","author":"Moritz","year":"2019","journal-title":"J. Immunol. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.jim.2013.11.014","article-title":"Non-specific binding in solid phase immunoassays for autoantibodies correlates with inflammation markers","volume":"403","author":"Duus","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_40","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_41","first-page":"94","article-title":"All-Russian Consensus on Diagnosis and Treatment of Celiac Disease in Children and Adults","volume":"89","author":"Parfenov","year":"2017","journal-title":"Ter. Arkhiv"},{"key":"ref_42","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_43","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"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4988\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:38:39Z","timestamp":1760031519000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/11\/4988"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,22]]},"references-count":43,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["ijms26114988"],"URL":"https:\/\/doi.org\/10.3390\/ijms26114988","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,5,22]]}}}