Undergrad student Northwestern Univ. Chicago, Illinois, United States
Disclosure(s):
Sadie Hergert-Atkinson: No financial relationships to disclose
Introduction/Rationale: Dipyridamole, a phosphodiesterase inhibitor used for stroke prevention, has emerging evidence as an NLRP3 inflammasome inhibitor. Because NEK7–NLRP3 interactions drive IL-1β/IL-18 release in autoinflammatory disease and may accelerate clonal myeloid evolution, we investigated whether low-dose dipyridamole could modulate inflammasome activity in a patient with adult-onset Still’s disease (AOSD) overlap and pre-MDS features.
Methods: A patient with CAPS/AOSD overlap, germline TP53 loss, and early marrow abnormalities was treated with dipyridamole 25 mg twice daily. Biomarkers including ferritin, VEGF, and lipid profiles were tracked over two years. Cytokine panels, bone marrow immunohistochemistry, and genetic data were used to correlate clinical and molecular findings.
Results: Dipyridamole restored VEGF expression, which had been undetectable, normalized ferritin after two years of elevation, and stabilized lipid abnormalities resistant to prior IL-1 blockade. Inflammatory symptoms improved in parallel with biomarker correction. Mechanistic correlations included increased intracellular cAMP, reduced NF-κB priming, attenuation of mitochondrial ROS, and disruption of NEK7–NLRP3 binding, consistent with published models. Biomarker shifts suggested improved macrophage function and reduced IL-1β/IL-18 activity.
Conclusion: This case shows that dipyridamole, a widely used cardiovascular agent, can function as an NEK7–NLRP3 inflammasome modulator in human disease. By restoring VEGF, ferritin, and lipid balance, dipyridamole reduced systemic inflammation in a patient at risk for myeloid transformation. These findings support further study of biomarker-guided dipyridamole therapy in autoinflammatory conditions with hematologic involvement.
