Acute chest syndrome (ACS), a life-threatening complication of sickle cell disease (SCD), may be driven by overactivation of the complement system, according to new research. The study suggests that complement inhibitors, already used in clinical settings, could help prevent or treat ACS.
ACS is a form of acute lung injury and a leading cause of death in people with SCD. Despite its severity, current treatment is limited to supportive care, due to limited understanding of its underlying causes.
Researchers found that the complement pathway, part of the innate immune system, is activated during ACS in both patients with SCD and in a mouse model. Haemolysis, a common feature of SCD and a known trigger for ACS, was shown to drive strong complement activation in mice.
The study also demonstrated that artificial activation of the complement system could induce ACS, while genetic deletion of the complement protein C3 or treatment with a C5 inhibitor protected mice from developing the condition, even after haemolysis.
These results show that complement activation plays a key role in ACS and point to complement-blocking drugs as a promising therapeutic option. The findings offer a new direction for the treatment of ACS, one of the most serious complications in sickle cell disease.
Helena Bradbury, EMJ
Reference
Chonat S et al. Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target. Sci Transl Med. 2025 Jul;17(807):eadl4922.
