{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T07:38:28Z","timestamp":1792222708287,"version":"4.4.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,18]],"date-time":"2023-09-18T00:00:00Z","timestamp":1694995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi\u2019s sarcoma (KS), a multicentric angio-proliferative cancer commonly associated with Human Immunodeficiency Virus (HIV) infection. KS pathogenesis is a multifactorial condition hinged on immune dysfunction yet the mechanisms underlying the risk of developing KS in HHV-8 seropositive adults remains unclear. Here we explored whether soluble markers of HIV-1-related systemic immune activation (SIA) and angiogenesis (VEGF and FGF acidic) are involved in the pathogenesis of KS in adults with HHV8.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaound\u00e9, Cameroon. CD3+\/CD4+ T cell counts and HIV-1 plasma viral load were determined using the Pima Analyzer and the RT-PCR technique, respectively. Plasma levels of SIA biomarkers (sCD163, sCD25\/IL-2R\u03b1, and sCD40\/TNFRSF5) and biomarkers of progression to KS (VEGF and FGF acidic) were measured using the Luminex assay. Seropositivity (IgG) for HHV-8 was determined using the ELISA method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, 20.2% (20\/99) of HIV-1 infected and 20% (12\/60) of HIV-1 uninfected participants were seropositive for HHV8. Levels of sCD163, sCD25\/IL-2R\u03b1, sCD40\/TNFRSF5, and FGF acidic were higher in the HIV-1 and HHV8 co-infection groups compared to the HIV-1 and HHV8 uninfected groups (all P &amp;lt;0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (r<jats:sub>s<\/jats:sub> = 0.58, P =0.0067) and sCD40\/TNFRSF5 (r<jats:sub>s<\/jats:sub> = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40\/TNFRSF5 (r<jats:sub>s<\/jats:sub> = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (r<jats:sub>s<\/jats:sub> =0.25, P = 0.03 and r<jats:sub>s<\/jats:sub> = 0.30, P = 0.006 respectively), sCD25\/IL-2R\u03b1 (r<jats:sub>s<\/jats:sub> = 0.5, P &amp;lt;0.0001 and r<jats:sub>s<\/jats:sub> = 0.55, P &amp;lt;0.0001 respectively) and sCD40\/TNFRSF5 (r<jats:sub>s<\/jats:sub> = 0.7, P &amp;lt;0.0001 and r<jats:sub>s<\/jats:sub> = 0.59, P &amp;lt;0.0001 respectively) and even in patients that were virally suppressed sCD25\/IL-2R\u03b1 (r<jats:sub>s<\/jats:sub> = 0.39, P = 0.012 and r<jats:sub>s<\/jats:sub> = 0.53, P = 0.0004 respectively) and sCD40\/TNFRSF5 (r<jats:sub>s<\/jats:sub> = 0.81, P &amp;lt;0.0001 and r<jats:sub>s<\/jats:sub> = 0.44, P = 0.0045 respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that although the development of KS in PLWH is multifactorial, HIV-associated SIA might be among the key drivers in coinfections with HHV8 and is independent of the patients\u2019 viremic status.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2023.1216480","type":"journal-article","created":{"date-parts":[[2023,9,19]],"date-time":"2023-09-19T07:37:15Z","timestamp":1695109035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Soluble biomarkers of HIV-1-related systemic immune activation are associated with high plasma levels of growth factors implicated in the pathogenesis of Kaposi sarcoma in adults"],"prefix":"10.3389","volume":"14","author":[{"given":"Benderli Christine","family":"Nana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livo Forgu","family":"Esemu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Ebangha","family":"Besong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick Hyacinthe Nyasse","family":"Atchombat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ogai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Th\u00e9r\u00e8se M. Patricia","family":"Sobgui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris Marco Mbianda","family":"Nana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reine Medouen Ndeumou","family":"Seumko\u2019o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Honor\u00e9","family":"Awanakan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel Loni","family":"Ekali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rose Gana Fomban","family":"Leke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigefumi","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishomwa 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