PLASMA PROTEOMIC PROFILE OF OSTEONECROSIS IN SICKLE CELL ANEMIA PATIENTS AND THE INFLUENCE OF HYDROXYUREA THERAPY

@article{santos2026plasma,
  title = {{PLASMA PROTEOMIC PROFILE OF OSTEONECROSIS IN SICKLE CELL ANEMIA PATIENTS AND THE INFLUENCE OF HYDROXYUREA THERAPY}},
  author = {Gabriel Lúcio Guimarães DOS SANTOS and Maria Luiza De Lima VITORINO and Josivan Barbosa DE FARIAS and Thais Helena Chaves BATISTA and Gabriela Da Silva ARCANJO and Aderson Araújo DOS SANTOS and Sara Teresinha Olalla SAAD and Roberto Afonso DA SILVA and Antônio Roberto Lucena DE ARAÚJO and Marcos André Cavalcanti BEZERRA},
  journal = {Hematology, Transfusion and Cell Therapy},
  year = {2026},
  month = oct,
  doi = {10.1016/j.htct.2026.106692},
  url = {https://doi.org/10.1016/j.htct.2026.106692},
  note = {CC BY},
}

TY  - JOUR
TI  - PLASMA PROTEOMIC PROFILE OF OSTEONECROSIS IN SICKLE CELL ANEMIA PATIENTS AND THE INFLUENCE OF HYDROXYUREA THERAPY
AU  - Gabriel Lúcio Guimarães DOS SANTOS
AU  - Maria Luiza De Lima VITORINO
AU  - Josivan Barbosa DE FARIAS
AU  - Thais Helena Chaves BATISTA
AU  - Gabriela Da Silva ARCANJO
AU  - Aderson Araújo DOS SANTOS
AU  - Sara Teresinha Olalla SAAD
AU  - Roberto Afonso DA SILVA
AU  - Antônio Roberto Lucena DE ARAÚJO
AU  - Marcos André Cavalcanti BEZERRA
PY  - 2026
DA  - 2026/10/23
JO  - Hematology, Transfusion and Cell Therapy
DO  - 10.1016/j.htct.2026.106692
UR  - https://doi.org/10.1016/j.htct.2026.106692
AB  - Introduction: Sickle cell anemia (SCA) is a monogenic disease caused by a mutation in the beta globin gene that ultimately leads to the sickling of erythrocytes. This alteration predisposes to vaso-occlusive and hemolytic events that cause several clinical manifestations, including osteonecrosis (ON), one of the most common complications in SCA. The molecular mechanisms involved in the pathophysiology of ON remain poorly understood. Most patients with SCA are treated with hydroxyurea (HU), however, questions remain regarding its benefits and role in preventing ON. In this context, proteomic analysis may contribute to provide insights into the pathophysiology of ON in SCA, as well as the impact of HU therapy. Objectives: To evaluate the plasma proteomic profile of SCA patients with and without ON and the influence of HU on this profile. Methods: Plasma samples from 40 adult SCA patients followed at the Hemotherapy Foundation of Pernambuco (HEMOPE) were stratified into four groups according to ON status and HU treatment. The groups consisted of SCA individuals with and without ON, subdivided into those who had been using HU for at least six months and those who were not using it. Samples from each group were pooled, resulting in four pools that were subsequently subjected to analysis. Prior to proteomic analysis, plasma samples underwent albumin and IgG depletion, quantification, clean-up, and enzymatic digestion using trypsin. Analysis was performed using high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) in triplicates of the four experimental pools. DAPs were identified and functional enrichment analyses were performed using Progenesis QI, OmicScope, and RStudio, with UniProt and GeneOntology as databases. Results: A total of 137 differentially accumulated proteins (DAPs) were quantified across the four experimental groups. Comparative analysis indicated that the groups exhibited significantly distinct proteomic profiles. In individuals with ON, DAP evaluation revealed an increase in proteins associated with complement system hyperactivation and related to a hypercoagulable state, characterized by elevated levels of proteins with prothrombotic functions, including prothrombin, and complement components. Conversely, a decrease in plasminogen and vitamin K-dependent protein S was demonstrated, reflecting impaired thrombotic control and compromised tissue remodeling processes in ON-affected areas. Regarding HU therapy, data indicate that its use influences the regulation of antioxidant and inflammatory pathways, as evidenced by increased hemopexin levels. However, HU therapy did not affect the levels of proteins essential for angiogenesis, cell anchorage, and the restoration of damaged bone structure, such as Insulin-like growth factor-binding protein complex acid labile subunit (IGFALS) and Fibronectin (FN1). Conclusion: This study proposes potential molecular mechanisms involved in the pathophysiology of ON in SCA and their relationship with HU treatment. The evidence demonstrates that ON may be associated with an imbalance between coagulation regulation and immune system activation. These mechanisms should be confirmed in future studies through the validation of proteomic data using complementary techniques.
SN  - 2531-1379
SN  - 2531-1387
ER  -