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Immune parameters (IP) have been extensively studied to distinguish between latent tuberculosis (LTBI) and active tuberculosis (TB).\n                    <jats:italic>Objective<\/jats:italic>\n                    . To determine the IP associated with LTBI, compared to active TB and individuals not infected by\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    published in literature.\n                    <jats:italic>Methods<\/jats:italic>\n                    . We conducted a systematic search using Google Scholar and PubMed databases, combining the MeSH terms latent tuberculosis,\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    , cytokines, and biological markers, with the free terms, biomarkers and cytokines. Spanish, English, and Portuguese articles comparing the concentration of IP associated with LTBI, either in plasma\/serum or in vitro, in adults and nonimmunocompromised versus individuals with TB or without\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    infection between 2006 July and 2018 July were included. Two blinded reviewers carried out the searches, read the abstracts, and selected the articles for analysis. Participants\u2019 information, diagnostic criteria, IP, detection methods, and biases were collected.\n                    <jats:italic>Results<\/jats:italic>\n                    . We analyzed 36 articles (of 637 abstracts) with 93 different biomarkers in different samples. We found 24 parameters that were increased only in active TB (TGF\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , CSF3, CSF2, CCL1 [I\u2010309], IL\u20107, TGF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    1, CCL3 [MIP\u20101\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ], sIL\u20102R, TNF\u2010\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , CCL7 [MCP\u20103], IFN\u2010\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , fractalkine, I\u2010TAG, CCL8 [MCP\u20102], CCL21 [6Ckine], PDGF, IL\u201022, VEGF\u2010A, LXA4, PGE2, PGF2\n                    <jats:italic>\u03b1<\/jats:italic>\n                    , sCD163, sCD14, and 15\u2010Epi\u2010LXA4), five were elevated in LTBI (IL\u20105, IL\u201017F, IL\u20101, CCL20 [MIP\u20103\n                    <jats:italic>\u03b1<\/jats:italic>\n                    ], and ICAM\u20101), and two substances were increased among uninfected individuals (IL\u201023 and basic FGF). We found high heterogeneity between studies including failure to account for the time\/illness of the individuals studied; varied samples and protocols; different clinical classification of TB; different laboratory methods for IP detection, which in turn leads to variable units of measurement and assay sensitivities; and selection bias regarding TST and booster effect. None of the studies adjusted the analysis for the effect of ethnicity.\n                    <jats:italic>Conclusions<\/jats:italic>\n                    . It is mandatory to harmonize the study of immune parameters for LTBI diagnosis. This systematic review is registered with PROSPERO\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/PROSPERO\/display_record.php?RecordID=73289\">CRD42017073289<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1155\/2020\/8074183","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T19:32:14Z","timestamp":1587497534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Gaps in Study Design for Immune Parameter Research for Latent Tuberculosis Infection: A Systematic Review"],"prefix":"10.1155","volume":"2020","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7482-2010","authenticated-orcid":false,"given":"Mariana","family":"Herrera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6775-151X","authenticated-orcid":false,"given":"Cristian","family":"Vera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4948-4707","authenticated-orcid":false,"given":"Yoav","family":"Keynan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6342-1812","authenticated-orcid":false,"given":"Zulma Vanessa","family":"Rueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,21]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00034-13"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiv757"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20090892"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.6.2249"},{"key":"e_1_2_11_5_2","unstructured":"WHO TDR Priorities for tuberculosis research October 2017 https:\/\/apps.who.int\/iris\/bitstream\/10665\/85888\/1\/9789241505970_eng.pdf."},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arbres.2011.06.018"},{"key":"e_1_2_11_7_2","unstructured":"Cellular and Molecular Immunology 9th October 2017 https:\/\/www.elsevier.com\/books\/cellular-and-molecular-immunology\/abbas\/978-0-323-47978-3."},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152483"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jit265"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.3855\/jidc.1925"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00111-09"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(02)00092-3"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.03.018"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/cvi.00038-13"},{"key":"e_1_2_11_15_2","volume-title":"Newcastle-Ottawa Scale Assessment of Cohort Studies","author":"Abou-Setta A. 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