Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.

@article{pitamartinez2026plasma,
  title = {{Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.}},
  author = {Carlos Pita-Martínez and Marta Rava and Ana Virseda-Berdices and Isidoro Martínez and Santiago Moreno and Carmen Elena Gómez Rodríguez and Carlos Armiñanzas and Álvaro Mena de Cea and Laura Gisbert Pérez and Rafael Rodríguez-Rosado and María Ángeles Jiménez-Sousa and Salvador Resino and Rubén Martín-Escolano and CoRIS cohort},
  journal = {Immunity \& ageing : I \& A},
  year = {2026},
  month = jul,
  doi = {10.1186/s12979-026-00583-7},
  url = {https://europepmc.org/article/MED/42907879},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Plasma biomarkers of immune regulation and senescence are associated with incident skeletal-related events in people with HIV: a case-cohort study.
AU  - Carlos Pita-Martínez
AU  - Marta Rava
AU  - Ana Virseda-Berdices
AU  - Isidoro Martínez
AU  - Santiago Moreno
AU  - Carmen Elena Gómez Rodríguez
AU  - Carlos Armiñanzas
AU  - Álvaro Mena de Cea
AU  - Laura Gisbert Pérez
AU  - Rafael Rodríguez-Rosado
AU  - María Ángeles Jiménez-Sousa
AU  - Salvador Resino
AU  - Rubén Martín-Escolano
AU  - CoRIS cohort
PY  - 2026
DA  - 2026/07/01
JO  - Immunity & ageing : I & A
DO  - 10.1186/s12979-026-00583-7
UR  - https://europepmc.org/article/MED/42907879
AB  - 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.
SN  - 1742-4933
ER  -