{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T13:12:04Z","timestamp":1759497124769,"version":"3.41.2"},"reference-count":67,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81973663"],"award-info":[{"award-number":["81973663"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of the study was to provide an overview of the existing evidence on non\u2010genetic biomarkers for ankylosing spondylitis (AS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this umbrella review, we searched PubMed and Web of Science from database inception to October 31, 2020. Systematic reviews and meta\u2010analyses of observational studies investigating the associations between any non\u2010genetic biomarkers and AS were included. We estimated summary standardized mean difference (SMD) along with 95% confidence interval (CI), <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> statistic, 95% prediction interval (PI), and assessed small\u2010study effects and excess significance bias. The study was registered in PROSPERO with registration number of CRD42020218240.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 1276 publications were identified, of which 21 articles covering 43 non\u2010genetic biomarkers were eligible for inclusion. Evidence of 22 (51%) non\u2010genetic biomarkers exhibited a nominally significant effect (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) on AS, and 7 associations (14%) showed small\u2010study effects. The associations of platelet count (SMD: 0.53, 95% CI: 0.36 to 0.71) and serum interleukin (IL)\u201023 levels (SMD = 2.03, 95% CI: 1.27 to 2.79) with AS presented highly suggestive evidence, while circulating IL\u201017 levels (SMD = 2.36, 95% CI: 1.71, 3.01) and Treg\/PBMC ratio (SMD = \u22120.75, 95% CI: \u22121.06 to \u22120.44) presented suggestive evidence. However, these associations showed large or very large between\u2010study heterogeneity, suggesting an indefinite direction for the effect when 95% PIs were considered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>No convincing evidence supported the existence of a non\u2010genetic biomarker for AS. Some highly suggestive associations might be affected by bias, therefore, promising non\u2010genetic biomarkers for AS remain limited at least based on the current evidence from observational studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcla.24759","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T03:46:16Z","timestamp":1667965576000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non\u2010genetic biomarkers for ankylosing spondylitis: An umbrella review"],"prefix":"10.1002","volume":"36","author":[{"given":"Changming","family":"Lv","sequence":"first","affiliation":[{"name":"School of the Fourth Clinical Medicine Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ding","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of the Fourth Clinical Medicine Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyang","family":"Meng","sequence":"additional","affiliation":[{"name":"School of the Fourth Clinical Medicine Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaohui","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengping","family":"Wen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3644-9160","authenticated-orcid":false,"given":"Yingying","family":"Mao","sequence":"additional","affiliation":[{"name":"School of Public Health Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406182"},{"issue":"2","key":"e_1_2_8_3_1","first-page":"263","article-title":"Incidence and prevalence of axial spondyloarthritis: methodologic challenges and gaps in the literature","volume":"36","author":"Bohn R","year":"2018","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11136-016-1345-z"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-021-05679-7"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/lycdc8"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31591-4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.630791"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.06.026"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/08820139.2019.1567531"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.07.152"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70267-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(86)90046-2"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-127-9-199711010-00008"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.322.7280.226"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0b013e31821b506e"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.2307\/3001666"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.1186"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-985X.2008.00552.x"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn204"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d4002"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/1740774507079441"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmp.2013.03.002"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115530"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j4008"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30181-6"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1313476110"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2017.12.050"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10165-009-0230-9"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.3109\/09537100903470306"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm8020230"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.01835"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1271-6"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1439-1"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10229"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.623874"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.637829"},{"issue":"12","key":"e_1_2_8_39_1","first-page":"15927","article-title":"Associations between serum levels of interleukin\u201023 and the susceptibility and development of ankylosing spondylitis: a meta\u2010analysis","volume":"10","author":"Han RF","year":"2017","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-020-00804-4"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1008038"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00393-018-0472-z"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1551"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/1756-185X.13494"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3794"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.24395"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.23343"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30418"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.608900"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-018-0729-1"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00051"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2019.1704714"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/1058738"},{"key":"e_1_2_8_54_1","first-page":"8709804","article-title":"Meta\u2010analysis of changes in the number and proportion of regulatory T cells in patients with ankylosing spondylitis","volume":"2020","author":"Li M","year":"2020","journal-title":"Biomed Res Int"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2014.08.040"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000001174"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.December.16.7"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2016.05.006"},{"issue":"10","key":"e_1_2_8_59_1","first-page":"17362","article-title":"Elevated serum levels of IL\u20106 and IL\u201017 may associate with the development of ankylosing spondylitis","volume":"8","author":"Liu W","year":"2015","journal-title":"Int J Clin Exp Med"},{"key":"e_1_2_8_60_1","first-page":"1","article-title":"Oxidative and antioxidative stress linked biomarkers in ankylosing spondylitis: a systematic review and meta\u2010analysis","volume":"2020","author":"Li JX","year":"2020","journal-title":"Oxid Med Cell Longev"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106948"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2018.1564165"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2017.09.029"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-019-00542-z"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011531"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1080\/14397595.2019.1645373"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.03.010"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2016.12"}],"container-title":["Journal of Clinical Laboratory Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.24759","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcla.24759","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcla.24759","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T11:23:50Z","timestamp":1692530630000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcla.24759"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":67,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1002\/jcla.24759"],"URL":"https:\/\/doi.org\/10.1002\/jcla.24759","archive":["Portico"],"relation":{},"ISSN":["0887-8013","1098-2825"],"issn-type":[{"type":"print","value":"0887-8013"},{"type":"electronic","value":"1098-2825"}],"subject":[],"published":{"date-parts":[[2022,11,8]]},"assertion":[{"value":"2022-05-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e24759"}}