{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:40:18Z","timestamp":1756269618848,"version":"3.44.0"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T00:00:00Z","timestamp":1756252800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Saliva biomarkers provide a convenient and noninvasive method for diagnosing immune and genetic disorders. One such biomarker is adenosine deaminase 2 (ADA2), an enzyme that converts adenosine into inosine and is elevated in cancer and immune diseases. Currently, ADA2 activity can be used to diagnose pleural tuberculosis. Recently, we developed an ELISA assay that detects ADA2 in saliva. This test has been successfully employed to diagnose adenosine deaminase 2 deficiency (DADA2) and potentially to identify individuals with head and neck cancer. DADA2 is a rare genetic disease that can lead to systemic vasculitis, early onset stroke, bone marrow failure, and\/or immunodeficiency. A rapid, simple, and affordable point-of-care (POC) test would significantly aid in diagnosing DADA2 and facilitate appropriate treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we created a novel colloidal gold-based immunochromatographic strip (ICS) containing polyclonal antigen-purified anti-ADA2 antibodies. The ADA2 rapid antigen test (RAT) was calibrated precisely to detect ADA2 in the saliva of healthy individuals, while those with ADA2 deficiency received negative results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The test successfully confirmed DADA2 in nine patients with different pathogenic mutations in ADA2, while 58 of 59 healthy donors tested positive for ADA2. <\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>The ADA2 rapid antigen test reliably screens patients with autoimmune disorders, accurately diagnosing DADA2. This test can also be used to diagnose pleural tuberculosis or other diseases with significantly elevated ADA2 levels.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1633219","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:56Z","timestamp":1756268036000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A rapid antigen test to detect adenosine deaminase 2 (ADA2) in biological fluids and its application in clinical diagnostics"],"prefix":"10.3389","volume":"16","author":[{"given":"Weiping","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qing","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jose M.","family":"Porcel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengxiang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey V.","family":"Zavialov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1205750","article-title":"Purinergic signaling during inflammation","volume":"367","author":"Eltzschig","year":"2012","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"418","DOI":"10.3390\/biom12030418","article-title":"Adenosine-metabolizing enzymes, adenosine kinase and adenosine deaminase, in cancer","volume":"12","author":"Zhulai","year":"2022","journal-title":"Biomolecules"},{"key":"B3","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1007\/s11684-024-1067-5","article-title":"Adenosine deaminase 2 regulates the activation of the toll-like receptor 9 in response to nucleic acids","volume":"18","author":"Dong","year":"2024","journal-title":"Front Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.2174\/138945012800564095","article-title":"Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders","volume":"13","author":"Antonioli","year":"2012","journal-title":"Curr Drug Targets"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.928438","article-title":"ELISA based assays to measure adenosine deaminases concentration in serum and saliva for the diagnosis of ADA2 deficiency and cancer","volume":"13","author":"Luo","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1007\/s11684-024-1110-6","article-title":"Intracellular concentration of ADA2 is a marker for monocyte differentiation and activation","volume":"19","author":"Dong","year":"2025","journal-title":"Front Med"},{"key":"B7","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ccm.2012.11.002","article-title":"Pleural fluid biomarkers: beyond the Light criteria","volume":"34","author":"Porcel","year":"2013","journal-title":"Clin Chest Med"},{"key":"B8","article-title":"The diagnostic utility of adenosine deaminase isoenzymes in tuberculous pleural effusions","volume":"13","author":"Zemlin","year":"2009","journal-title":"Int J Tuberc Lung Dis"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307361","article-title":"Early-onset stroke and vasculopathy associated with mutations in ADA2","volume":"370","author":"Zhou","year":"2014","journal-title":"N Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.15894","article-title":"Evaluation and management of deficiency of adenosine deaminase 2: an international consensus statement","volume":"6","author":"Lee","year":"2023","journal-title":"JAMA Netw Open"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00918-8","article-title":"Mechanisms of vascular inflammation in deficiency of adenosine deaminase 2 (DADA2)","volume":"44","author":"Lee","year":"2022","journal-title":"Semin Immunopathol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2021-0324","article-title":"Analytical validation of an automated assay for the measurement of adenosine deaminase (ADA) and its isoenzymes in saliva and a pilot evaluation of their changes in patients with SARS-CoV-2 infection","volume":"59","author":"Franco-Martinez","year":"2021","journal-title":"Clin Chem Lab Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.3389\/fimmu.2025.1646134","article-title":"Developing and validating anti-ADA2 single-chain antibodies coupled to alkaline phosphatase for diagnosing pleural tuberculosis [Original Research]","volume":"6","author":"Skaldin","year":"2025","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2357-0","article-title":"Human adenosine deaminases ADA1 and ADA2 bind to different subsets of immune cells","volume":"74","author":"Kaljas","year":"2017","journal-title":"Cell Mol Life Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.020255-0","article-title":"High-titre retroviral vector system for efficient gene delivery into human and mouse cells of haematopoietic and lymphocytic lineages","volume":"91","author":"Wu","year":"2010","journal-title":"J Gen Virol"},{"key":"B16","first-page":"67","article-title":"Inclusion of high molecular weight dextran in calcium phosphate-mediated transfection significantly improves gene transfer efficiency","volume":"53","author":"Wu","year":"2007","journal-title":"Cell Mol Biol (Noisy-le-grand)"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1633219\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T04:13:57Z","timestamp":1756268037000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1633219\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,27]]},"references-count":16,"alternative-id":["10.3389\/fimmu.2025.1633219"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1633219","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,27]]},"article-number":"1633219"}}