{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T08:38:06Z","timestamp":1771663086972,"version":"3.50.1"},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T00:00:00Z","timestamp":1643414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871283"],"award-info":[{"award-number":["81871283"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81601765"],"award-info":[{"award-number":["81601765"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019349","name":"Nanjing Medical Science and Technique Development Foundation","doi-asserted-by":"publisher","award":["JQX20004"],"award-info":[{"award-number":["JQX20004"]}],"id":[{"id":"10.13039\/501100019349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019349","name":"Nanjing Medical Science and Technique Development Foundation","doi-asserted-by":"publisher","award":["YKK21066"],"award-info":[{"award-number":["YKK21066"]}],"id":[{"id":"10.13039\/501100019349","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019349","name":"Nanjing Medical Science and technique Development Foundation","doi-asserted-by":"crossref","award":["QRX17142"],"award-info":[{"award-number":["QRX17142"]}],"id":[{"id":"10.13039\/501100019349","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Immunol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Adult-onset Still's disease (AOSD) is a systemic inflammatory disease of unknown etiology, lacking specific diagnosis and disease activity evaluation indicators. This study will analyze the activity and clinical significance of Adenosine deaminase (ADA) in AOSD patients.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Totally 53 AOSD patients, 60 patients with other autoimmune diseases including systemic lupus erythematosus (SLE), sjogren syndrome (SS) and rheumatoid arthritis (RA), as well as 60 healthy subjects were included in this study. AOSD activity was determined by Pouchot score. We analyzed the correlation between ADA activity and clinical parameters. In addition, the correlation between ADA activity and disease activity score was also analyzed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This study showed that the activity of ADA in AOSD patients was significantly higher than that of healthy controls, SLE, SS and RA patient groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). The ADA activity of AOSD patients decreased significantly after systemic treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Correlation analysis showed that ADA activity was positively correlated with ALT(<jats:italic>r<\/jats:italic>\u2009=\u20090.54, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), AST (<jats:italic>r<\/jats:italic>\u2009=\u20090.82, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and serum ferritin (<jats:italic>r<\/jats:italic>\u2009=\u20090.67, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). ADA activity was negatively correlated with white blood cell (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.42, <jats:italic>p<\/jats:italic>\u2009=\u20090.002) and platelet counts (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.44, <jats:italic>p<\/jats:italic>\u2009=\u20090.001). We also found a significant positive correlation between the activity of ADA and Pouchot score in AOSD patients (<jats:italic>r<\/jats:italic>\u2009=\u20090.51, <jats:italic>p<\/jats:italic>\u2009=\u20090.001). Receiver operating characteristic (ROC) curve analysis showed that ADA activity had a sensitivity of 93.3%, and a specificity of 83% for the diagnosis of AOSD, with an area under the curve of 0.93.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>This study showed that serum ADA activity can be used as a potential biomarker for AOSD diagnosis and disease activity assessment.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12865-022-00477-5","type":"journal-article","created":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T02:02:24Z","timestamp":1643421744000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Increased serum adenosine deaminase activity in patients with adult-onset Still's disease"],"prefix":"10.1186","volume":"23","author":[{"given":"Zhiye","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linyu","family":"Geng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LiLi","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyan","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,1,29]]},"reference":[{"key":"477_CR1","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00296-009-1291-y","volume":"30","author":"V Bagnari","year":"2010","unstructured":"Bagnari V, Colina M, Ciancio G, Govoni M, Trotta F. Adult-onset Still\u2019s disease. Rheumatol Int. 2010;30:855\u201362. https:\/\/doi.org\/10.1007\/s00296-009-1291-y.","journal-title":"Rheumatol Int"},{"key":"477_CR2","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1080\/1744666X.2018.1465821","volume":"14","author":"S Mitrovic","year":"2018","unstructured":"Mitrovic S, Fautrel B. Complications of adult-onset Still\u2019s disease and their management. Expert Rev Clin Immu. 2018;14:351\u201365. https:\/\/doi.org\/10.1080\/1744666X.2018.1465821.","journal-title":"Expert Rev Clin Immu"},{"key":"477_CR3","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/j.cca.2012.01.027","volume":"413","author":"D Chen","year":"2012","unstructured":"Chen D, Chen Y, Lan J, Tzang B, Lin C, Hsu T. Significant association of past parvovirus B19 infection with cytopenia in both adult-onset Still\u2019s disease and systemic lupus erythematosus patients. Clin Chim Acta. 2012;413:855\u201360. https:\/\/doi.org\/10.1016\/j.cca.2012.01.027.","journal-title":"Clin Chim Acta"},{"key":"477_CR4","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1080\/1744666X.2018.1533403","volume":"14","author":"P Ruscitti","year":"2018","unstructured":"Ruscitti P, Giacomelli R. Pathogenesis of adult onset still\u2019s disease: current understanding and new insights. Expert Rev Clin Immunol. 2018;14:965\u201376. https:\/\/doi.org\/10.1080\/1744666X.2018.1533403.","journal-title":"Expert Rev Clin Immunol"},{"key":"477_CR5","doi-asserted-by":"publisher","first-page":"369","DOI":"10.3389\/fphar.2017.00369","volume":"8","author":"S Colafrancesco","year":"2017","unstructured":"Colafrancesco S, Priori R, Valesini G, Argolini L, Baldissera E, Bartoloni E, et al. Response to interleukin-1 inhibitors in 140 Italian patients with adult-onset still\u2019s disease: a multicentre retrospective observational study. Front Pharmacol. 2017;8:369. https:\/\/doi.org\/10.3389\/fphar.2017.00369.","journal-title":"Front Pharmacol"},{"key":"477_CR6","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1136\/ard.2005.042143","volume":"65","author":"P Efthimiou","year":"2006","unstructured":"Efthimiou P, Paik PK, Bielory L. Diagnosis and management of adult onset Still\u2019s disease. Ann Rheum Dis. 2006;65:564\u201372. https:\/\/doi.org\/10.1136\/ard.2005.042143.","journal-title":"Ann Rheum Dis"},{"key":"477_CR7","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.3899\/jrheum.100247","volume":"37","author":"M Rau","year":"2010","unstructured":"Rau M, Schiller M, Krienke S, Heyder P, Lorenz H, Blank N. Clinical manifestations but not cytokine profiles differentiate adult-onset Still\u2019s disease and sepsis. J Rheumatol. 2010;37:2369.","journal-title":"J Rheumatol"},{"key":"477_CR8","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1097\/00005792-199103000-00004","volume":"70","author":"J Pouchot","year":"1991","unstructured":"Pouchot J, Sampalis JS, Beaudet F, Carette S, Decary F, Salusinsky-Sternbach M, et al. Adult Still\u2019s disease: manifestations, disease course, and outcome in 62 patients. Medicine (Baltimore). 1991;70:118\u201336.","journal-title":"Medicine (Baltimore)"},{"key":"477_CR9","doi-asserted-by":"publisher","first-page":"3876","DOI":"10.3748\/wjg.v23.i21.3876","volume":"23","author":"M Torgutalp","year":"2017","unstructured":"Torgutalp M, Efe C, Babaoglu H, Kav T. Relationship between serum adenosine deaminase levels and liver histology in autoimmune hepatitis. World J Gastroenterol. 2017;23:3876\u201382. https:\/\/doi.org\/10.3748\/wjg.v23.i21.3876.","journal-title":"World J Gastroenterol"},{"key":"477_CR10","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1038\/nrrheum.2016.178","volume":"13","author":"BN Cronstein","year":"2017","unstructured":"Cronstein BN, Sitkovsky M. Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. Nat Rev Rheumatol. 2017;13:41\u201351. https:\/\/doi.org\/10.1038\/nrrheum.2016.178.","journal-title":"Nat Rev Rheumatol"},{"key":"477_CR11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.imlet.2018.04.006","volume":"205","author":"L Antonioli","year":"2019","unstructured":"Antonioli L, Fornai M, Blandizzi C, Pacher P, Hask\u00f3 G. Adenosine signaling and the immune system: When a lot could be too much. Immunol Lett. 2019;205:9\u201315. https:\/\/doi.org\/10.1016\/j.imlet.2018.04.006.","journal-title":"Immunol Lett"},{"key":"477_CR12","doi-asserted-by":"publisher","first-page":"842","DOI":"10.2174\/138945012800564095","volume":"13","author":"L Antonioli","year":"2012","unstructured":"Antonioli L, Colucci R, La Motta C, Tuccori M, Awwad O, Da Settimo F, et al. Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Curr Drug Targets. 2012;13:842.","journal-title":"Curr Drug Targets"},{"key":"477_CR13","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2020.102709","volume":"20","author":"Z Gao","year":"2021","unstructured":"Gao Z, Wang X, Zhang H, Lin F, Liu C, Dong K. The roles of adenosine deaminase in autoimmune diseases. Autoimmun Rev. 2021;20: 102709. https:\/\/doi.org\/10.1016\/j.autrev.2020.102709.","journal-title":"Autoimmun Rev"},{"key":"477_CR14","doi-asserted-by":"publisher","first-page":"6509","DOI":"10.3892\/mmr.2015.4285","volume":"12","author":"J Huang","year":"2015","unstructured":"Huang J, He Y, Chen M, Du J, Li G, Li S, et al. Adenosine deaminase and adenosine kinase expression in human glioma and their correlation with glioma-associated epilepsy. Mol Med Rep. 2015;12:6509\u201316. https:\/\/doi.org\/10.3892\/mmr.2015.4285.","journal-title":"Mol Med Rep"},{"key":"477_CR15","first-page":"561","volume":"51","author":"MC P\u00e9rez-Aguilar","year":"2010","unstructured":"P\u00e9rez-Aguilar MC, Goncalves L, Ibarra A, Bonfante-Cabarcas R. Adenosine deaminase as costimulatory molecule and marker of cellular immunity. Investig Clin. 2010;51:561.","journal-title":"Investig Clin"},{"key":"477_CR16","doi-asserted-by":"publisher","DOI":"10.5812\/jjm.21760","volume":"8","author":"S Salmanzadeh","year":"2015","unstructured":"Salmanzadeh S, Tavakkol H, Bavieh K, Alavi SM. Diagnostic value of serum adenosine deaminase (ADA) level for pulmonary tuberculosis. Jundishapur J Microbiol. 2015;8: e21760. https:\/\/doi.org\/10.5812\/jjm.21760.","journal-title":"Jundishapur J Microbiol"},{"key":"477_CR17","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1097\/00004836-200609000-00009","volume":"40","author":"A Riquelme","year":"2006","unstructured":"Riquelme A, Calvo M, Salech F, Valderrama S, Pattillo A, Arellano M, et al. Value of adenosine deaminase (ADA) in ascitic fluid for the diagnosis of tuberculous peritonitis: a meta-analysis. J Clin Gastroenterol. 2006;40:705\u201310. https:\/\/doi.org\/10.1097\/00004836-200609000-00009.","journal-title":"J Clin Gastroenterol"},{"key":"477_CR18","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s00408-016-9891-2","volume":"194","author":"RM Terra","year":"2016","unstructured":"Terra RM, Antonangelo L, Mariani AW, de Oliveira RL, Teixeira LR, Pego-Fernandes PM. Pleural fluid adenosine deaminase (ADA) predicts survival in patients with malignant pleural effusion. Lung. 2016;194:681\u20136. https:\/\/doi.org\/10.1007\/s00408-016-9891-2.","journal-title":"Lung"},{"key":"477_CR19","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s12026-018-8984-9","volume":"66","author":"ZW Gao","year":"2018","unstructured":"Gao ZW, Zhao GH, Zhang Z, Huang J, Li ZY, Zhang HZ, et al. Serum adenosine deaminase activity is increased in systemic lupus erythematosus patients and correlated with disease activity. Immunol Res. 2018;66:299\u2013304. https:\/\/doi.org\/10.1007\/s12026-018-8984-9.","journal-title":"Immunol Res"},{"key":"477_CR20","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1007\/s100670170005","volume":"20","author":"S Hitoglou","year":"2001","unstructured":"Hitoglou S, Hatzistilianou M, Gougoustamou D, Athanassiadou F, Kotsis A, Catriu D. Adenosine deaminase activity and its isoenzyme pattern in patients with juvenile rheumatoid arthritis and systemic lupus erythematosus. Clin Rheumatol. 2001;20:411\u20136. https:\/\/doi.org\/10.1007\/s100670170005.","journal-title":"Clin Rheumatol"},{"key":"477_CR21","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1136\/annrheumdis-2019-216030","volume":"79","author":"PY Lee","year":"2020","unstructured":"Lee PY, Schulert GS, Canna SW, Huang Y, Sundel J, Li Y, et al. Adenosine deaminase 2 as a biomarker of macrophage activation syndrome in systemic juvenile idiopathic arthritis. Ann Rheum Dis. 2020;79:225\u201331. https:\/\/doi.org\/10.1136\/annrheumdis-2019-216030.","journal-title":"Ann Rheum Dis"},{"key":"477_CR22","first-page":"424","volume":"19","author":"M Yamaguchi","year":"1992","unstructured":"Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still\u2019s disease. J Rheumatol. 1992;19:424.","journal-title":"J Rheumatol"},{"key":"477_CR23","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1007\/s00296-012-2532-z","volume":"33","author":"C Xun","year":"2013","unstructured":"Xun C, Xun C, Zhao Y, Zhao Y, Hu ZJ, Hu ZJ. Potential role of adenosine deaminase in the diagnosis of adult-onset Still\u2019s disease. Rheumatol Int. 2013;33:1255\u20138. https:\/\/doi.org\/10.1007\/s00296-012-2532-z.","journal-title":"Rheumatol Int"},{"key":"477_CR24","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.autrev.2015.01.004","volume":"14","author":"P Ruscitti","year":"2015","unstructured":"Ruscitti P, Cipriani P, Di Benedetto P, Ciccia F, Liakouli V, Carubbi F, et al. Increased level of H-ferritin and its imbalance with L-ferritin, in bone marrow and liver of patients with adult onset Still\u2019s disease, developing macrophage activation syndrome, correlate with the severity of the disease. Autoimmun Rev. 2015;14:429\u201337. https:\/\/doi.org\/10.1016\/j.autrev.2015.01.004.","journal-title":"Autoimmun Rev"},{"key":"477_CR25","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/nrc.2017.86","volume":"17","author":"D Vijayan","year":"2017","unstructured":"Vijayan D, Young A, Teng M, Smyth MJ. Targeting immunosuppressive adenosine in cancer. Nat Rev Cancer. 2017;17:709\u201324. https:\/\/doi.org\/10.1038\/nrc.2017.86.","journal-title":"Nat Rev Cancer"},{"key":"477_CR26","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.humimm.2020.12.005","volume":"82","author":"A Churov","year":"2021","unstructured":"Churov A, Zhulai G. Targeting adenosine and regulatory T cells in cancer immunotherapy. Hum Immunol. 2021;82:270\u20138. https:\/\/doi.org\/10.1016\/j.humimm.2020.12.005.","journal-title":"Hum Immunol"}],"container-title":["BMC Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-022-00477-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12865-022-00477-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12865-022-00477-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T02:04:10Z","timestamp":1643421850000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcimmunol.biomedcentral.com\/articles\/10.1186\/s12865-022-00477-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,29]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["477"],"URL":"https:\/\/doi.org\/10.1186\/s12865-022-00477-5","relation":{},"ISSN":["1471-2172"],"issn-type":[{"value":"1471-2172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,29]]},"assertion":[{"value":"14 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 January 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Research and Ethics Committee of Nanjing Drum Tower Hospital, according to the principles of the Declaration of Helsinki, and each subject provided written informed consent for participation in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"4"}}