{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:10:02Z","timestamp":1765278602314,"version":"3.46.0"},"posted":{"date-parts":[[2025,12,2]]},"group-title":"HIV\/AIDS","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T00:00:00Z","timestamp":1764633600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,12,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Sepsis causes high mortality among people living with HIV in Africa, yet immune response data are limited. We identified immune subphenotypes of adults with sepsis and a high prevalence of HIV in East Africa.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We determined the association of serum cytokine and antibody concentrations with CD4+ T-cell and blood lactate concentration, tuberculosis, and 30-day mortality with K-means clustering, principal component analysis (PCA), and logistic regression. We validated results in a separate cohort of adults with sepsis in East Africa.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Of 208 participants in the discovery cohort, 117 (56%) were female and 175 (84%) were living with HIV, with a mean (\u00b1SD) age of 35 (\u00b110) years. Participants with tuberculosis had higher concentrations of G-CSF, IFN-\u03b3, IL-1\u03b2, IL-6, IL-8, and MCP1MCAF, whereas mortality was associated with higher concentrations of G-CSF, IL-6, IL-8, IL-10, and MIP-1\u03b2, and lower concentrations of IgM antibodies against oxidation-specific epidopes (IgM\n                    <jats:sup>OSE<\/jats:sup>\n                    ). PCA identified G-CSF, IL-5, IL-6, IL-8, and IL-13 as the main contributors to tuberculosis, and IL-4, IL-6, IL-8, IL-12, and IL-13 as the main contributors to mortality. Comprehensive biomarker and clinical and multivariable models accurately predicted tuberculosis (AUC = 0.84) and mortality (AUC = 0.78), which was replicated in the validation cohort. Cross-testing showed that the tuberculosis model delineated pathogen-specific immune activation, while the mortality model represented non-pathogen-specific immune dysregulation.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    In adults with sepsis and high HIV prevalence in East Africa, tuberculosis was associated with pathogen-specific inflammation, and mortality was associated with broader immune dysregulation and diminished IgM\n                    <jats:sup>OSE<\/jats:sup>\n                    antibody responses.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.11.29.25341077","type":"posted-content","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T11:05:26Z","timestamp":1765278326000},"source":"Crossref","is-referenced-by-count":0,"title":["Immune subphenotypes of tuberculosis and mortality in adults with sepsis and a high prevalence of HIV in East Africa"],"prefix":"10.64898","author":[{"given":"Louisa","family":"Edwards","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2425-9394","authenticated-orcid":false,"given":"Shevin T.","family":"Jacob","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Majwala","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Banura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott K.","family":"Heysell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stellah","family":"Mpagama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Null","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania A.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arestaricky","family":"Rimoy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bibie","family":"Said","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin","family":"Nuwagira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Conrad","family":"Muzoora","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2731-3299","authenticated-orcid":false,"given":"Jeffrey M.","family":"Sturek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher C.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Otoupalova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025120902574880000_2025.11.29.25341077v1.1","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1093\/cid\/ciy472","article-title":"Etiology of Sepsis in Uganda Using a Quantitative Polymerase Chain Reaction-based TaqMan Array Card","volume":"68","year":"2019","journal-title":"Clin Infect Dis"},{"key":"2025120902574880000_2025.11.29.25341077v1.2","unstructured":"GBD 2021 Global Sepsis Collaborators : Global, regional, and national sepsis incidence and mortality, 1990-2021: a systematic analysis. 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