{"doi":"10.3389/fimmu.2023.1216480","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","abstract":"Background Human Herpesvirus-8 (HHV-8) is the etiologic agent of Kaposi’s 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. Methodology Blood samples from 99 HIV-1 infected and 60 HIV-1 uninfected adults were collected in Yaoundé, 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-2Rα, 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. Results 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-2Rα, 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 <0.05). In addition, Higher plasma levels of VEGF correlated with sCD163 (r s = 0.58, P =0.0067) and sCD40/TNFRSF5 (r s = 0.59, P = 0.0064), while FGF acidic levels correlated with sCD40/TNFRSF5 (r s = 0.51, P = 0.022) in co-infected. In HIV-1 mono-infected donors, VEGF and FGF acidic levels correlated with sCD163 (r s =0.25, P = 0.03 and r s = 0.30, P = 0.006 respectively), sCD25/IL-2Rα (r s = 0.5, P <0.0001 and r s = 0.55, P <0.0001 respectively) and sCD40/TNFRSF5 (r s = 0.7, P <0.0001 and r s = 0.59, P <0.0001 respectively) and even in patients that were virally suppressed sCD25/IL-2Rα (r s = 0.39, P = 0.012 and r s = 0.53, P = 0.0004 respectively) and sCD40/TNFRSF5 (r s = 0.81, P <0.0001 and r s = 0.44, P = 0.0045 respectively). Conclusion 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’ viremic status.","journal":"Frontiers in Immunology","year":2023,"id":383720,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9674,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":436310,"name":"Livo F. Esemu","orcid":"0000-0002-0793-2826","position":1,"is_corresponding":false},{"id":977805,"name":"Michael Besong","orcid":null,"position":2,"is_corresponding":false},{"id":1151124,"name":"Derrick Hyacinthe Nyasse Atchombat","orcid":null,"position":3,"is_corresponding":false},{"id":895036,"name":"Kazuhiro Ogai","orcid":"0000-0002-3462-9320","position":4,"is_corresponding":false},{"id":1151125,"name":"Thérèse M. Patricia Sobgui","orcid":null,"position":5,"is_corresponding":false},{"id":1151126,"name":"Chris Marco Mbianda Nana","orcid":null,"position":6,"is_corresponding":false},{"id":517100,"name":"Reine Medouen Ndeumou Seumko’o","orcid":null,"position":7,"is_corresponding":false},{"id":1151127,"name":"Honoré Awanakan","orcid":null,"position":8,"is_corresponding":false},{"id":436309,"name":"Gabriel Loni Ekali","orcid":"0000-0003-3693-5097","position":9,"is_corresponding":false},{"id":436315,"name":"Rose G. F. Leke","orcid":"0000-0002-5973-1145","position":10,"is_corresponding":false},{"id":895038,"name":"Shigefumi Okamoto","orcid":"0000-0001-9359-380X","position":11,"is_corresponding":false},{"id":69472,"name":"Lishomwa C. Ndhlovu","orcid":"0000-0001-5427-4187","position":12,"is_corresponding":false},{"id":516475,"name":"Rosette Megnekou","orcid":"0000-0003-0692-5197","position":13,"is_corresponding":false},{"id":895575,"name":"Benderli Christine Nana","orcid":null,"position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:17:29.050285Z","pmid":"37809059","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}