{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:32:11Z","timestamp":1788348731867,"version":"build-2803163510"},"reference-count":84,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"807","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,7,16]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1126\/scitranslmed.adl4922","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T17:58:22Z","timestamp":1752688702000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":23,"title":["Complement is activated in patients with acute chest syndrome caused by sickle cell disease and represents a therapeutic target"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5909-0800","authenticated-orcid":true,"given":"Satheesh","family":"Chonat","sequence":"first","affiliation":[{"name":"Aflac Cancer and Blood Disorders Center, Children\u2019s Healthcare of Atlanta, Atlanta, GA 30322, USA."},{"name":"Department of Pediatrics, Emory University School of Medicine, 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