biostudies-literatureRoh TNational Research Foundation of Korea (NRF)Korea Health Industry Development InstituteNational Research Foundation of KoreaKorea Health Industry Development Institute (KHIDI)1342https://www.ebi.ac.uk/biostudies/studies/S-EPMC11794430biostudies-literatureUnknown16(1)Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and FNature communicationsFucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study.PMC11794430RS-2020-KH008690RS-2023-00255021RS-2023-00208127RS-2023-00227274Yamasaki SAhn YKim GLee SIJo EKChoi HLee SGShimizu TRoh TRyu GPark SYJung SSChung JNakano MKim ISChung CMiyoshi EKim YJJu SPark CfalseFucosylated haptoglobin promotes inflammation via Mincle in sepsis: an observational study.Haptoglobin (Hp) scavenges cell-free hemoglobin and correlates with the prognosis of human sepsis, a life-threatening systemic inflammatory condition. Despite extensive research on Hp glycosylation as a glyco-biomarker for cancers, understanding glycosylated modifications of Hp in sepsis patients (SPs) remains limited. Our study reveals elevated levels of terminal fucosylation at Asn207 and Asn211 of Hp in SP plasma, along with heightened inflammatory responses, compared to healthy controls (trial registration NCT05911711). Fucosylated (Fu)-Hp purified from SPs upregulates inflammatory cytokines and chemokines, along with NLRP3 inflammasome activation. Single-cell RNA sequencing identifies a distinct macrophage-like cell population with increased expressions of inflammatory mediators and F2025-01-01T00:00:00Z2025 Feb2026-06-01T20:11:45.08Z2025-04-04T07:26:47.663ZS-EPMC117944303990498310.1038/s41467-025-56524-3