Inhibition of the complement pathway might prevent acute chest syndrome, one of the severe complications of sickle cell disease, according to new US research published in Science Translational Medicine.
The researchers say they have identified how the breakdown of diseased red blood cells triggers acute chest syndrome (ACS) and hypoxia. In blood samples donated by people with sickle cell disease experiencing ACS, they discovered unusually high activity of protein components of the complement pathway – an ancient fast-acting immune reaction that normally helps neutralise microbes.
In studies with mouse models of sickle cell disease, the researchers tested genetically disrupting complement proteins, or using existing drugs that block the C5 complement protein. They found blocking the complement pathway in this way protects mice from ACS and hypoxia, boosts lung function and improves survival.
Study leader Dr Sean Stowell, of the Department of Pathology at Brigham and Women's Hospital, Massachusetts, said: “Despite ACS being the leading cause of mortality in patients with sickle cell disease, we can currently only offer supportive care to our patients.
“Our study offers potential targets for therapeutic intervention for this devastating condition.”
The researchers say that randomised control trials will be needed to evaluate the impact of different complement inhibitors on preventing ACS in sickle cell disease patients.
Source:
Chonat S, Jones JA, Patel SR, Briones WM, Schoettler ML, Maarouf M, Jeffers LA, Adisa O, Tan F, Fields E, Sterling MS, Jajosky RP, Verkerke H, Graciaa SH, Foppiani EM, Fasano RM, Zerra PE, Qiu Y, Arthur CM, Lam WA, Ofori-Acquah SF, Koval M, Joiner CH, Archer DR, Stowell SR. (2025) “Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target.” Science Translational Medicine, 18 July 2025, doi: 10.1126/scitranslmed.adl4922.
Link: www.science.org/doi/10.1126/scitranslmed.adl4922
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