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The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18\u00a0years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as \u201cNon TB\u201d, 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13\u00a0IU\/ml vs 1.995, (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090,0001), those with asymptomatic TB from those with symptomatic TB (1.01\u00a0IU\/ml vs 0.115\u00a0IU\/ml, <jats:italic>p<\/jats:italic> 0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Conversely, CD4\u2009+\u2009and CD8\u2009+\u2009responses were similar in all groups of patients, although active TB patients had higher CD4\u2009+\u2009responses and LTBI higher CD8\u2009+\u2009responses.<\/jats:p><jats:p><jats:italic>\u00a0 Conclusion<\/jats:italic>: HBHA-based IGRA, combined with CD4\u2009+\u2009and CD8\u2009+\u2009responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy.\n<jats:table-wrap><jats:table><jats:tbody>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is Known:<\/jats:bold><jats:italic>\u2022 Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS.<\/jats:italic>.<jats:italic>\u2022 New immunological assays with prognostic value are highly needed<\/jats:italic>.<\/jats:td>\n                    <\/jats:tr>\n                    <jats:tr>\n                      <jats:td colspan=\"2\"><jats:bold>What is New:<\/jats:bold><jats:italic>\u2022 HBHA-based IGRA, combined with CD4<\/jats:italic>+ <jats:italic>and CD8<\/jats:italic>+ <jats:italic>responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children.<\/jats:italic>.<jats:italic>\u2022 HBHA-based IGRA, combined with CD4<\/jats:italic>+ <jats:italic>and CD8<\/jats:italic>+ <jats:italic>responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children.<\/jats:italic>.<\/jats:td>\n                    <\/jats:tr>\n                  <\/jats:tbody><\/jats:table><\/jats:table-wrap><\/jats:p>","DOI":"10.1007\/s00431-023-04844-1","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T07:02:55Z","timestamp":1677481375000},"page":"2155-2167","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Commercially available CD4\u2009+\u2009and CD8\u2009+\u2009IFN-\u03b3 release assays combined with an HBHA-induced IGRA improve the characterization of the tuberculosis spectrum and monitoring of treatment in children"],"prefix":"10.1007","volume":"182","author":[{"given":"Danilo","family":"Buonsenso","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Delogu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"del Carmen Pereyra Boza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavio","family":"De Maio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivana","family":"Palucci","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Martino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Pata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Sanguinetti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Valentini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Sali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"key":"4844_CR1","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/S1473-3099(08)70182-8","volume":"8","author":"SM Newton","year":"2008","unstructured":"Newton SM, Brent AJ, Anderson S, Whittaker E, Kampmann B (2008) Paediatric tuberculosis. 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