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oai:repisalud.isciii.es:20.500.12105/277402026-09-26T00:16:20Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608col_20.500.12105_19609
Repisalud author Pita-Martínez, Carlos author Rava, Marta author Virseda-Berdices, Ana author Martinez, Isidoro author Moreno, Santiago author Gómez Rodríguez, Carmen Elena author Armiñanzas, Carlos author Mena de Cea, Álvaro author Gisbert Pérez, Laura author Rodríguez-Rosado, Rafael author Jimenez-Sousa, Maria Angeles author Resino, Salvador author Martín-Escolano, Rubén funder Instituto de Salud Carlos III funder Agencia Estatal de Investigación (España) funder Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas) funder Ministerio de Ciencia, Innovación y Universidades (España) funder Comunidad de Madrid (España) 2026-09-25T13:58:41Z 2026-09-25T13:58:41Z 2026-07-27 Pita-Martínez, C., Rava, M., Virseda-Berdices, A. et al. Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study. Immun Ageing (2026). https://doi.org/10.1186/s12979-026-00583-7. 1742-4933 https://hdl.handle.net/20.500.12105/27740 10.1186/s12979-026-00583-7 Immunity & Ageing Background: persistent immune dysregulation in people with HIV (PWH) on antiretroviral therapy (ART) contributes to an increased risk of skeletal-related events (SREs), serving as a critical paradigm for understanding accelerated aging and age-related diseases. We investigated the association between plasma biomarkers of immune regulation and senescence with incident SRE risk and evaluated potential effect modification by sex. Methods: in a case-cohort study nested within the Spanish CoRIS cohort (65 incident SRE cases; 252 subcohort, including 5 overlapping cases), we quantified 24 baseline biomarkers of immune checkpoints and senescence-associated secretory phenotype factors. We estimated adjusted hazard ratios (aHR) using Borgan II-weighted cause-specific Cox regression models adjusted for clinical confounders (age, region of origin, prior AIDS diagnosis, CD4 + T-cell count, coinfections, and lifestyle factors). Sex-biomarker interactions were assessed as exploratory endpoints. Results: nineteen biomarkers were independently associated with increased SRE risk (p < 0.05 & q < 0.10). Angiogenic factors (VEGF-A; aHR = 1.94; 95% CI, 1.40–2.68), immune checkpoints (PD-L2; aHR = 1.95; 95% CI, 1.09–3.49), and tissue remodeling markers (MMP-1; aHR = 1.91; 95% CI, 1.08–3.39) displayed independent associations, alongside consistent signals for TIM-3, PD-L1, and IL-8. Pairwise correlation analysis demonstrated clustering between checkpoints and inflammatory cytokines. Exploratory interaction analysis indicated that sex modified these associations; signals for seven markers (e.g., IL-1α, VEGF-A) were stronger in females, although the limited number of events warrants caution. Conclusions: circulating biomarkers of immune exhaustion, inflammation, and senescence are independently associated with incident SREs in PWH on long-term ART. Our findings indicate a systemic pro-inflammatory signature and suggest that females exhibit higher sensitivity to inflammatory damage. eng HIV Skeletal-related events Biomarkers Cellular senescence Ageing Immune checkpoints Sex differences Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study. research article QWNlcHRhbmRvIGVzdGEgbGljZW5jaWEsIFVzdGVkIChlbCBhdXRvci9lcyBvIGVsIHByb3BpZXRhcmlvL3MgZGUgbG9zIGRlcmVjaG9zIGRlIGF1dG9yKSBjb25jZWRlIGEgUkVQSVNBTFVEIGVsIGRlcmVjaG8gbm8gZXhjbHVzaXZvIGRlIHJlcHJvZHVjaXIsIGNvbnZlcnRpciwgeS9vIGRpc3RyaWJ1aXIgc3UgZG9jdW1lbnRvIChpbmNsdXllbmRvIHN1IHJlc3VtZW4pIGEgbml2ZWwgbXVuZGlhbCBlbiBmb3JtYXRvIGRpZ2l0YWwsIGluY2x1eWVuZG8sIGF1ZGlvIHkgdsOtZGVvLCBhIHRyYXbDqXMgZGUgc3UgcmVwb3NpdG9yaW8gaW5zdGl0dWNpb25hbC4KClVzdGVkIGFjZXB0YSBxdWUgUkVQSVNBTFVEIHB1ZWRlLCBzaW4gYWx0ZXJhciBzdSBjb250ZW5pZG8sIGNvbnZlcnRpciBzdSBkb2N1bWVudG8gYSBjdWFscXVpZXIgb3RybyBmb3JtYXRvIGRpZ2l0YWwgZGUgZGF0b3MsIGF1ZGlvIHkgdmlkZW8sIGNvbiBlbCBwcm9ww7NzaXRvIGRlIHF1ZSBwdWVkYSBzZXIgYWxvamFkbyBlbiBlbCByZXBvc2l0b3Jpby4KClVzdGVkIGVzdMOhIGRlIGFjdWVyZG8gY29uIHF1ZSBSRVBJU0FMVUQgcHVlZGEgY29uc2VydmFyIG3DoXMgZGUgdW5hIGNvcGlhIGRlIGVzdGUgZG9jdW1lbnRvIHBhcmEgYXNlZ3VyYXIgc3Ugc2VndXJpZGFkLCBwcmVzZXJ2YWNpw7NuIHkgYWNjZXNvLgoKVXN0ZWQgZGVjbGFyYSBxdWUgZWwgZG9jdW1lbnRvIGVzIHVuIHRyYWJham8gb3JpZ2luYWwsIHkgcXVlIHRpZW5lIGVsIGRlcmVjaG8gZGUgb3RvcmdhciBsb3MgZGVyZWNob3MgY29udGVuaWRvcyBlbiBlc3RhIGxpY2VuY2lhLiBUYW1iacOpbiBkZWNsYXJhIHF1ZSBzdSBwZXRpY2nDs24gbm8gaW5mcmluZ2UgbG9zIGRlcmVjaG9zIGRlIGF1dG9yIGRlIG5hZGllLgoKU2kgZWwgZG9jdW1lbnRvIGNvbnRpZW5lIG1hdGVyaWFsZXMgcGFyYSBsb3MgcXVlIG5vIHNlIHRpZW5lbiBsb3MgZGVyZWNob3MgZGUgYXV0b3IsIHVzdGVkIGRlY2xhcmEgcXVlIGhhIG9idGVuaWRvIGVsIHBlcm1pc28gc2luIHJlc3RyaWNjacOzbiBkZWwgcHJvcGlldGFyaW8gZGUgbG9zIGRlcmVjaG9zIHkgcXVlIGVuIGRpY2hvIG1hdGVyaWFsLCBlc3TDoSBjbGFyYW1lbnRlIGlkZW50aWZpY2FkYSB5IHJlY29ub2NpZGEgc3UgYXV0b3LDrWEgZGVudHJvIGVsIHRleHRvIG8gZGVsIGNvbnRlbmlkbyBkZSBkaWNobyBkb2N1bWVudG8uCgpTaSBlbCBlbnbDrW8gc2UgYmFzYSBlbiB1biB0cmFiYWpvIHF1ZSBoYSBzaWRvIHBhdHJvY2luYWRvIG8gYXBveWFkbyBwb3IgdW5hIGFnZW5jaWEgdSBvcmdhbml6YWNpw7NuIGRpc3RpbnRhIGEgUkVQSVNBTFVELCB1c3RlZCBhY2VwdGEgcXVlIGhhIGN1bXBsaWRvIGNvbiBlbCBkZXJlY2hvIGRlIHJldmlzacOzbiB5IG90cmFzIG9ibGlnYWNpb25lcyByZXF1ZXJpZGFzIHBvciBjb250cmF0byBvIGFjdWVyZG8uCgpSRVBJU0FMVUQgaWRlbnRpZmljYXLDoSBjbGFyYW1lbnRlIHN1KHMpIG5vbWJyZShzKSBjb21vIGF1dG9yKHMpIG8gcHJvcGlldGFyaW8ocykgZGVsIGRvY3VtZW50bywgeSBubyBoYXLDoSBuaW5ndW5hIGFsdGVyYWNpw7NuLCBleGNlcHRvIHNlZ8O6biBsbyBwZXJtaXRpZG8gcG9yIGVzdGEgbGljZW5jaWEuCg== URL https://repisalud.isciii.es/bitstreams/aaeac547-3367-4d2a-ba62-9a0cdd16cccf/download File MD5 64da52ddb85afbaa02995c4b02208449 2045439 application/pdf PlasmaBiomarkersImmuneRegulation_2026.pdf URL https://repisalud.isciii.es/bitstreams/3e85c8a2-8a3f-43ce-9322-bfdf1e6fd833/download File MD5 00e55722eda1c2cbf67285a9bfa6e152 490313 application/zip Supplementary_PlasmaBiomarkersImmuneRegulation_2026.zip