PLASMA LIPIDOMIC REMODELING ASSOCIATED WITH RECURRENT SICKLE CELL LEG ULCERS

@article{mateos2026plasma,
  title = {{PLASMA LIPIDOMIC REMODELING ASSOCIATED WITH RECURRENT SICKLE CELL LEG ULCERS}},
  author = {Sheila De Oliveira Garcia MATEOS and Marcos Eduardo Souza ABREU and Fábio Eudes LEAL and Felipe Custódio Carvalho DOS SANTOS and André Rolim BELISÁRIO and Brian Scott CUSTER and Carla Luana DINARDO and Luiz De Melo Amorim FILHO and Scott BOWLER and Lishomwa NDHLOVU and Paula Fraiman Blatyta CASELLI and Dahra TELES and Shannon KELLY and Álex Aparecido Rosini SILVA and Ester Cerdeira SABINO},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.106691},
  url = {https://doi.org/10.1016/j.htct.2026.106691},
  note = {CC BY},
}

TY  - JOUR
TI  - PLASMA LIPIDOMIC REMODELING ASSOCIATED WITH RECURRENT SICKLE CELL LEG ULCERS
AU  - Sheila De Oliveira Garcia MATEOS
AU  - Marcos Eduardo Souza ABREU
AU  - Fábio Eudes LEAL
AU  - Felipe Custódio Carvalho DOS SANTOS
AU  - André Rolim BELISÁRIO
AU  - Brian Scott CUSTER
AU  - Carla Luana DINARDO
AU  - Luiz De Melo Amorim FILHO
AU  - Scott BOWLER
AU  - Lishomwa NDHLOVU
AU  - Paula Fraiman Blatyta CASELLI
AU  - Dahra TELES
AU  - Shannon KELLY
AU  - Álex Aparecido Rosini SILVA
AU  - Ester Cerdeira SABINO
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.106691
UR  - https://doi.org/10.1016/j.htct.2026.106691
AB  - Introduction: Sickle cell leg ulcers (SCLUs) are disabling complications of sickle cell disease (SCD), but the circulating lipid alterations associated with recurrent ulcer status remain poorly characterized. Aim: This study aimed to characterize the plasma lipidomic landscape associated with recurrent SCLUs and identify candidate lipid signatures related to ulcer recurrence. Methodology: We performed an exploratory untargeted plasma lipidomics study in 129 participants from the multicenter REDS-III Brazil SCD cohort, including 72 individuals with recurrent SCLUs and 57 SCD controls without documented ulcer history or follow-up ulcer episodes. Plasma samples were analyzed by LC–MS in negative ion mode using data-independent acquisition. Exploratory feature selection was performed within the training set using nominal unadjusted testing, and supervised classification was evaluated as a secondary, hypothesis-generating analysis using an internal hold-out test split. Results: After quality filtering, 2,419 molecular features were retained. Training-set exploratory screening identified 181 candidate features, of which 44 were structurally annotated and carried forward for biological interpretation. Most annotated candidates were lipids, including glycerophospholipids, fatty acyls, sphingolipids, one steroid, and one glycerolipid. Recurrent SCLUs were characterized by higher lysophospholipids and oxygenated fatty acids/oxylipin-related metabolites, whereas controls showed higher FAHFAs, sphingolipids, and cholesterol sulfate. Discussion: These patterns support candidate lipid axes related to inflammatory lipid remodeling, oxidative lipid modification, and membrane-endothelial homeostasis. In secondary classification analysis, Random Forest showed the highest apparent discrimination in the internal hold-out test split (AUC=0.85), but performance estimates were interpreted cautiously because of the modest test-set size and exploratory feature selection strategy. Conclusion: Untargeted plasma lipidomics identified candidate lipid remodeling patterns associated with recurrent SCLU status in SCD. These findings should not be interpreted as validated biomarkers or causal mediators, but they nominate lipid classes and representative species for targeted quantification, covariate-aware validation, external replication, and longitudinal studies with detailed ulcer phenotyping.
SN  - 2531-1379
SN  - 2531-1387
ER  -