Exploring the Mechanisms of Cyclosporine Therapy in Aplastic Anemia: A Data-Independent Acquisition Proteomics Approach.

RATIONALE: Clinically, cyclosporine (CsA) plays a crucial role in the treatment of aplastic anemia (AA) and has demonstrated significant therapeutic efficacy. We applied DIA-based quantitative proteomics to analyze plasma protein profiles in AA patients, aiming to identify proteins and pathways modulated by CsA, thereby elucidating its therapeutic mechanisms.

METHODS

Plasma samples from three AA patients pre- and post-CsA treatment underwent data-independent acquisition proteomics. DEPs were identified using fold-change thresholds. Gene Ontology, KEGG, and STRING analyses revealed functional pathways and hub proteins, which were validated by ELISA in 13 AA patients. Molecular docking assessed CsA-core protein binding affinities.

RESULTS

Compared to healthy people, AA patients exhibited 303 differential proteins, enriched in pathways related to oxidative stress, cellular adhesion, and energy dysregulation. Post-CsA treatment, 107 DEPs were identified, linked to redox balance and structural remodeling. Forty-eight proteins overlapped, with GAPDH, SOD1, CFL1, and ACTG1 as core targets. ELISA confirmed expression differences, and molecular docking showed strong CsA binding affinities to these proteins.

CONCLUSIONS

Significant protein expression differences between AA patients and healthy controls suggest immune-related pathways, including metabolism, oxidative stress, and cell structure, as key treatment targets. CsA may regulate these to intervene in AA progression.