Science translational medicine · 2025
Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод пока не подготовлен
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Chonat Satheesh, Jones Jayre A, Patel Seema R, Briones William M, Schoettler Michelle L, Maarouf Maya, Jeffers Lauren A, Adisa Olufolake, Tan Fang, Fields Earl, Sterling Morgan S, Jajosky Ryan P, Verkerke Hans, Graciaa Sara H, Foppiani Elisabetta M, Fasano Ross M, Zerra Patricia E, Qiu Yongzhi, Arthur Connie M, Lam Wilbur A, Ofori-Acquah Solomon F, Koval Michael, Joiner Clinton H, Archer David R, Stowell Sean R
Аннотация
Despite being the first genetic disease described, sickle cell disease (SCD) continues to result in severe complications. Of these complications, acute chest syndrome (ACS), a form of acute lung injury, leads all-cause mortality. However, the pathophysiology of ACS remains incompletely understood, resulting in patients with ACS receiving only supportive measures. Here, we found that ACS is accompanied by activation of the complement pathway, an evolutionarily ancient innate immune system responsible for eliminating microbes. Using a well-defined preclinical model of SCD, hemolysis, a precursor of ACS, not only induced ACS but also drove robust complement activation. Artificial activation of complement alone similarly induced ACS, whereas genetic removal or pharmacological inhibition of complement rendered SCD mice resistant to ACS even after induction of hemolysis. These results demonstrate that complement drives ACS, establishing a link between SCD and this ancient form of immunity that provides an opportunity for targeted treatment of this complication.