PLASMA PROTEOMIC PROFILE OF PATIENTS WITH ACTIVE OR HEALED LEG ULCERS AND SICKLE CELL ANEMIA
- 1Universidade Federal de Pernambuco (UFPE), Recife, PE, Brazil
- 2Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brazil
Abstract
Introduction: Leg ulcers (LUs) are among the most debilitating chronic complications of sickle cell anemia (SCA), causing pain, functional impairment, and high recurrence rates. Although their etiology is multifactorial, the molecular mechanisms underlying ulcer development, healing, and recurrence remain poorly understood. Objectives: To characterize the plasma proteomic profile of patients with SCA according to LU status and identify biological pathways associated with ulcer activity and healing. Material and Methods: Plasma samples from 60 age and sex-matched adults with SCA were stratified into three groups (n=20 each): active leg ulcer (ALU), healed leg ulcer (HLU), and no history of leg ulcer (Control). Equal plasma aliquots from individuals within each group were combined to generate one pooled sample per group. Each pool was analyzed in technical triplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential protein abundance analysis was performed in a Python-based bioinformatics environment, followed by Gene Ontology (GO) functional enrichment analysis. Results: Compared with Controls, the ALU and HLU groups exhibited 13 and 49 differentially abundant proteins (DAPs), respectively, including 11 shared proteins. Both ulcer groups demonstrated coordinated alterations involving lipid metabolism, predominantly represented by apolipoproteins, together with dysregulation of hemostasis, vascular remodeling and tissue repair, and complement-related proteins. Proteins involved in platelet aggregation, plasminogen activation, and fibrinolysis were consistently decreased, whereas proteins associated with lipid transport and lipoprotein remodeling were increased in LUs groups. Direct comparison between ALU and HLU identified only two DAPs, mannose-binding lectin 2 (MBL2) and C-reactive protein (CRP), both more abundant in ALU, indicating that the principal molecular differences between active and healed ulcers are associated with acute inflammatory response and innate immune activation. Notably, the proteomic profile of patients with HLU was markedly more similar to ALU than to Controls, indicating persistent systemic molecular dysregulation despite apparent healing. Conclusion: These findings demonstrate that clinical wound closure does not fully restore systemic molecular homeostasis in SCA. Persistent alterations involving lipid metabolism, complement activation, hemostasis, and tissue remodeling suggest that biological recovery extends beyond wound closure and may contribute to the persistence and high recurrence of LUs. These results provide new insights into the molecular basis of LU pathophysiology and identify candidate biomarkers for future validation studies.
Related
- PLASMA PROTEOMIC PROFILE OF OSTEONECROSIS IN SICKLE CELL ANEMIA PATIENTS AND THE INFLUENCE OF HYDROXYUREA THERAPY
- Proteomic profiling of liver and plasma uncovers biomarkers and mechanisms in patients with primary biliary cholangitis
- Plasma proteomic profiling identifies country-specific diversity in visceral leishmaniasis patients across East Africa
- Assessment of functional profile and fatigue in Egyptian patients with active secondary progressive MS
- Biologically informed network-regularized sparse consensus clustering (BioNet-SPACC) identifies a continuous plasma proteomic axis in major depressive disorder
BibTeX
@article{batista2026plasma,
title = {{PLASMA PROTEOMIC PROFILE OF PATIENTS WITH ACTIVE OR HEALED LEG ULCERS AND SICKLE CELL ANEMIA}},
author = {Thais Helena Chaves BATISTA and Gabriela Da Silva ARCANJO and Madi Veiga DINIZ and Maria Luiza De Lima VITORINO and Josivan Barbosa DE FARIAS and Alexsandro Pedro DA SILVA and Fernando Ferreira COSTA and Roberto Afonso DA SILVA and Antonio Roberto LUCENA-ARAUJO and Marcos André Cavalcanti BEZERRA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106693},
url = {https://doi.org/10.1016/j.htct.2026.106693},
note = {CC BY},
}
RIS
TY - JOUR
TI - PLASMA PROTEOMIC PROFILE OF PATIENTS WITH ACTIVE OR HEALED LEG ULCERS AND SICKLE CELL ANEMIA
AU - Thais Helena Chaves BATISTA
AU - Gabriela Da Silva ARCANJO
AU - Madi Veiga DINIZ
AU - Maria Luiza De Lima VITORINO
AU - Josivan Barbosa DE FARIAS
AU - Alexsandro Pedro DA SILVA
AU - Fernando Ferreira COSTA
AU - Roberto Afonso DA SILVA
AU - Antonio Roberto LUCENA-ARAUJO
AU - Marcos André Cavalcanti BEZERRA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106693
UR - https://doi.org/10.1016/j.htct.2026.106693
AB - Introduction: Leg ulcers (LUs) are among the most debilitating chronic complications of sickle cell anemia (SCA), causing pain, functional impairment, and high recurrence rates. Although their etiology is multifactorial, the molecular mechanisms underlying ulcer development, healing, and recurrence remain poorly understood. Objectives: To characterize the plasma proteomic profile of patients with SCA according to LU status and identify biological pathways associated with ulcer activity and healing. Material and Methods: Plasma samples from 60 age and sex-matched adults with SCA were stratified into three groups (n=20 each): active leg ulcer (ALU), healed leg ulcer (HLU), and no history of leg ulcer (Control). Equal plasma aliquots from individuals within each group were combined to generate one pooled sample per group. Each pool was analyzed in technical triplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential protein abundance analysis was performed in a Python-based bioinformatics environment, followed by Gene Ontology (GO) functional enrichment analysis. Results: Compared with Controls, the ALU and HLU groups exhibited 13 and 49 differentially abundant proteins (DAPs), respectively, including 11 shared proteins. Both ulcer groups demonstrated coordinated alterations involving lipid metabolism, predominantly represented by apolipoproteins, together with dysregulation of hemostasis, vascular remodeling and tissue repair, and complement-related proteins. Proteins involved in platelet aggregation, plasminogen activation, and fibrinolysis were consistently decreased, whereas proteins associated with lipid transport and lipoprotein remodeling were increased in LUs groups. Direct comparison between ALU and HLU identified only two DAPs, mannose-binding lectin 2 (MBL2) and C-reactive protein (CRP), both more abundant in ALU, indicating that the principal molecular differences between active and healed ulcers are associated with acute inflammatory response and innate immune activation. Notably, the proteomic profile of patients with HLU was markedly more similar to ALU than to Controls, indicating persistent systemic molecular dysregulation despite apparent healing. Conclusion: These findings demonstrate that clinical wound closure does not fully restore systemic molecular homeostasis in SCA. Persistent alterations involving lipid metabolism, complement activation, hemostasis, and tissue remodeling suggest that biological recovery extends beyond wound closure and may contribute to the persistence and high recurrence of LUs. These results provide new insights into the molecular basis of LU pathophysiology and identify candidate biomarkers for future validation studies.
SN - 2531-1379
SN - 2531-1387
ER -