{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:17:05Z","timestamp":1789154225567,"version":"build-2803163510"},"reference-count":80,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T00:00:00Z","timestamp":1773360000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Shiga-like toxin-producing E. coli-induced hemolytic uremic syndrome (STEC-HUS) is a rare but severe disease characterized by microangiopathic hemolysis, thrombocytopenia, and renal failure. No specific therapy is available, and long-term complications are common. Growing evidence indicates that STEC-HUS is associated with excessive complement activation, however the impact on disease pathogenesis is still debated. This study investigated the involvement of the three complement pathways in STEC-HUS. We analyzed 37 patients during the acute phase and 24 patients after hospital discharge.\n                    <jats:italic>Ex-vivo<\/jats:italic>\n                    assays with patient sera and cultured microvascular endothelial cells demonstrated that acute-phase sera triggered abnormal C3 and C5b-9 deposition, leading to increased cell surface expression of vWF and P-selectin, which in turn promoted thrombus formation on endothelial cells. The factor B inhibitor iptacopan, but not inhibitors of classical or lectin pathways, effectively blocked complement deposition and prevented thrombus formation, highlighting the alternative pathway as a driver of complement dysregulation and microvascular thrombosis in acute STEC-HUS. Additionally, we observed persistent complement activation in a substantial subset of patients studied after hospital discharge, as indicated by abnormal C5b-9 formation. Notably, most of these patients had not achieved full remission, showing at least one hematologic abnormality and\/or elevated serum creatinine. These findings emphasize the pivotal role of complement overactivation in STEC-HUS pathogenesis and support the potential of alternative pathway inhibitors as promising therapeutic options. Moreover, our results underscore the potential of the\n                    <jats:italic>ex-vivo<\/jats:italic>\n                    tests as valuable tools for monitoring complement activity and clotting abnormalities over time, possibly facilitating detection and management of disease sequelae.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1749811","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T05:25:47Z","timestamp":1773379547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular determinants of STEC-HUS: from complement activation to microvascular thrombosis"],"prefix":"10.3389","volume":"17","author":[{"given":"Donata","family":"Santarsiero","sequence":"first","affiliation":[{"name":"Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Clinical Research Center for Rare Diseases Aldo e Cele Dacc\u00f2 and Centro Anna Maria Astori, Science and 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