PATTERNS OF LEUKOCYTE TELOMERE SHORTENING IN A LARGE BRAZILIAN COHORT OF PATIENTS WITH SICKLE CELL DISEASE

@article{oliveira2026patterns,
  title = {{PATTERNS OF LEUKOCYTE TELOMERE SHORTENING IN A LARGE BRAZILIAN COHORT OF PATIENTS WITH SICKLE CELL DISEASE}},
  author = {Théo Gremen OLIVEIRA and Carla Luana DINARDO and Mina Cintho OZAHATA and Natalia Vasconcelos DURAZZO and Sandra GUALANDRO and Shannon KELLY and Ester Cerdeira SABINO and Brian CUSTER and Vanderson ROCHA},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.106583},
  url = {https://doi.org/10.1016/j.htct.2026.106583},
  note = {CC BY},
}

TY  - JOUR
TI  - PATTERNS OF LEUKOCYTE TELOMERE SHORTENING IN A LARGE BRAZILIAN COHORT OF PATIENTS WITH SICKLE CELL DISEASE
AU  - Théo Gremen OLIVEIRA
AU  - Carla Luana DINARDO
AU  - Mina Cintho OZAHATA
AU  - Natalia Vasconcelos DURAZZO
AU  - Sandra GUALANDRO
AU  - Shannon KELLY
AU  - Ester Cerdeira SABINO
AU  - Brian CUSTER
AU  - Vanderson ROCHA
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.106583
UR  - https://doi.org/10.1016/j.htct.2026.106583
AB  - Background: Leukocyte telomere length (LTL) is a biomarker of biological aging and cumulative cellular stress. Chronic inflammation is a major driver of telomere shortening. Sickle cell disease (SCD) is characterized by lifelong inflammation resulting from chronic hemolysis, vaso-occlusion, and continuous immune activation. However, the effect of this persistent inflammatory state on LTL across the lifespan of SCD individuals remains poorly understood. Objectives: To characterize age-related LTL shortening in a large Brazilian cohort of patients with SCD and identify some clinical factors associated with shorter LTL. Methods: We analyzed 2,620 SCD individuals from the Brazilian cohort of the Recipient Epidemiology and Donor Evaluation Study (REDS-III). Whole-genome sequencing (WGS) was performed through the NHLBI the Trans-Omics for Precision Medicine (TOPMed) Program. LTL was measured by the TelSeq method corrected for sequencing batch effects, and expressed as adjusted LTL (aLTL). Linear regression models evaluated associations between aLTL and age, sex, hydroxyurea (HU) use, SCD type, hospitalization history and leukocyte counts. Results: The median age was 16-years (IQR: 9‒26; Range 0‒77). Genotypes included were HbSS (n = 1857, 70.9%), HbSC (n = 603, 23%), HbSβ⁰ (n = 72, 2.7%), HbSβ⁺ (n = 38, 1.5%), and other genotypes (n = 50, 1.9%). Median aLTL was 0.527 (IQR: 0.087–1.05). aLTL showed a moderate inverse correlation with age ( r = -0.414; r2:0.17; p-value < 2e-16) with no significant differences among SCD genotypes. The greatest decline occurred during the first three decades of life, with median aLTL decreasing by more than 50% between childhood and young adulthood (0–9 years: 0.911; 10–19 years: 0.637; 20–29 years: 0.357). In multivariate analysis, increasing age (β = -0.022 per year, p < 0.001), male sex (β = -0.131, p < 0.001), and HU use (β = -0.194, 95% CI -0.250 to -0.138; p < 0.001) were independently associated with shorter aLTL. No independent association was observed between SCD genotype and aLTL. Conclusion: In this large Brazilian SCD cohort LTL declined progressively with age, with the most pronounced shortening occurring during the first three decades of life. Telomere shortening was independent of SCD genotype but was associated with male sex. HU use was independently associated with shorter LTL although this finding may reflect confounding by disease severity. Therefore, we suggest that accelerated biological aging in SCD is driven primarily by cumulative disease-related stress rather than genotype and identify early adulthood as a critical period for telomere loss, warranting further longitudinal studies to determine its prognostic significance.
SN  - 2531-1379
SN  - 2531-1387
ER  -