{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:57:57Z","timestamp":1792144677464,"version":"4.4.0"},"reference-count":64,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":5,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Corticosteroid-binding globulin (CBG) is a serum glycoprotein that binds and delivers anti-inflammatory cortisol to inflammatory sites through neutrophil elastase-mediated proteolysis of an exposed reactive centre loop (RCL) on CBG. Timely and tissue-specific delivery of cortisol is critical to alleviate inflammation including in life-threatening septic shock conditions. Herein, we firstly summarise our recently published report of functional RCL O- and N-glycosylation events of serum CBG (Chernykh, J Biol Chem, 2023). A key finding of that published work was the LC\u2013MS\/MS-based discovery of RCL O-glycans at Thr342 and Thr345 of serum CBG and their inhibitory roles in neutrophil elastase-mediated RCL proteolysis. While these observations are of significance as they implicate RCL O-glycosylation as a potential regulator of cortisol delivery, the link to septic shock remains unexplored. To this end, we used a similar LC\u2013MS\/MS approach to profile the RCL O-glycosylation of CBG purified from serum of twelve septic shock patients. Serum CBG from all patients exhibited RCL O-glycosylation comprising (di)sialyl T (NeuAc1-2Gal1GalNAc1) core 1-type O-glycan structures decorating exclusively the Thr342 site. Importantly, relative to less severe cases, individuals presenting with the most severe illness displayed elevated RCL O-glycosylation upon ICU admission, suggesting a previously unknown link to septic shock severity. Overall, we have elucidated the coordinated RCL N- and O-glycosylation events of serum CBG, which improve our understanding of molecular mechanisms governing the timely and tissue-specific delivery of cortisol to inflammatory sites. This work provides clues to molecular aberrations and disease mechanisms underpinning septic shock.<\/jats:p>","DOI":"10.1093\/glycob\/cwaf013","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:25:31Z","timestamp":1741220731000},"source":"Crossref","is-referenced-by-count":3,"title":["RCL glycosylation of serum corticosteroid-binding globulin: implications in cortisol delivery and septic shock"],"prefix":"10.1093","volume":"35","author":[{"given":"Anastasia","family":"Chernykh","sequence":"first","affiliation":[{"name":"School of Natural Sciences, Macquarie University , 4 Wally\u2019s Walk, Macquarie Park, 2109, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7064-2728","authenticated-orcid":false,"given":"Zeynep","family":"Sumer-Bayraktar","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Macquarie University , 4 Wally\u2019s Walk, Macquarie Park, 2109, New South Wales ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica H","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Adelaide , Corner of George Street and North Terrace, Adelaide, 5000, South Australia ,","place":["Australia"]},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital , Port Road, Adelaide, 5000, South Australia ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily J","family":"Meyer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Adelaide , Corner of George Street and North Terrace, Adelaide, 5000, South Australia ,","place":["Australia"]},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital , Port Road, Adelaide, 5000, South Australia ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Torpy","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Adelaide , Corner of George Street and North Terrace, Adelaide, 5000, South Australia ,","place":["Australia"]},{"name":"Endocrine and Metabolic Unit, Royal Adelaide Hospital , Port Road, Adelaide, 5000, South Australia ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8327-6843","authenticated-orcid":false,"given":"Morten","family":"Thaysen-Andersen","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Macquarie University , 4 Wally\u2019s Walk, Macquarie Park, 2109, New South Wales ,","place":["Australia"]},{"name":"Institute for Glyco-core Research (iGCORE), Nagoya University , Furocho, Chikusa Ward, Nagoya, 464-8601, Aichi 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