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Interferon-gamma release assays (IGRAs) for tuberculosis screening quantify release of interferon-gamma by T-cells, and the difference between unstimulated and mitogen-stimulated T-cells is assessed for test validity. We assess this measure\u2019s relationship with all-cause mortality. We obtained the most recent negative and indeterminate outpatient IGRAs from a large health system along with demographics, frailty, lymphocyte count, and inflammatory markers. We removed individuals on hemodialysis or immunosuppressive medications. We assessed the association of mitogen-nil with mortality at 6\u00a0months, 1\u00a0year, and 5\u00a0years by Kaplan-Meier analysis and Cox regression. Among 16,104 individuals, reported mitogen-nil ranged from\u2009&lt;\u20090.01 to\u2009\u2265\u200910\u00a0IU\/mL, and median (IQR) age was 64 (57, 72). Cumulative mortality (95% CI) at 5\u00a0years was estimated at 28% (23%\u201333%) for values 0\u20131 versus 19% (18%\u201319%)\u2009\u2265\u200910. In Cox regression, relative to values\u2009\u2265\u200910, values from 0\u20131 had hazard ratios for mortality at 6\u00a0months, 1\u00a0year, and 5\u00a0years of 2.77 (1.47\u20135.22), 2.22 (1.41\u20133.50), and 1.76 (1.31\u20132.36). Among those with data, adding lymphocyte count did not alter associations. Lower T-cell response to mitogen stimulation in IGRAs is associated with greater mortality. This common test may provide additional information to risk-stratify patients and as a phenotype of impaired immune response.<\/jats:p>","DOI":"10.1007\/s11357-026-02221-y","type":"journal-article","created":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:28:35Z","timestamp":1777249715000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune activation from M. tuberculosis screening tests predicts mortality"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8223-5924","authenticated-orcid":false,"given":"Benjamin","family":"Seligman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8512-1641","authenticated-orcid":false,"given":"David A.","family":"Ganz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-992X","authenticated-orcid":false,"given":"Matthew Bidwell","family":"Goetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-167X","authenticated-orcid":false,"given":"David O.","family":"Beenhouwer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"issue":"2","key":"2221_CR1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.cell.2022.11.001","volume":"186","author":"C L\u00f3pez-Ot\u00edn","year":"2023","unstructured":"L\u00f3pez-Ot\u00edn C, Blasco MA, Partridge L, Serrano M, Kroemer G. 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