TS3 Asn347 corticosteroid-binding globulin (CBG) glycoform deficiency is associated with mortality in human septic shock

Abstract Context Corticosteroid binding globulin (CBG) deficiency is an independent predictor of intensive care unit (ICU) mortality in septic shock. CBG glycosylation at the Asn347 site affects neutrophil elastase cleavage susceptibility, altering CBG:cortisol binding affinity and may underlie this association. Objective To analyse CBG Asn347 glycoforms in patients with septic shock and determine their relationship to mortality and illness severity. Methods CBG Asn347 site glycosylation profiling was performed by mass spectrometry in 128 septic shock patients from a tertiary hospital ICU at day 1 and last day of admission up to 7 days. ICU and 28-day mortality were analysed by a COX proportional hazards model, sequentially correcting for illness severity (APACHE score) and total CBG (all glycoforms). Results Only triantennary trisialylated (TS3) Asn347 CBG glycoform concentrations were lower in ICU septic shock non-survivors than in survivors (29.74 vs 45.16 nmol/L, p = 0.007). On COX multivariate analysis correcting for APACHE score, lowest tertile of TS3 Asn347 CBG glycoform concentration (<27.9 nmol/L) was associated with increased ICU mortality (adj HR 2.7, 95% CI 1.2-6.2, p = 0.023) and was the only Asn347 glycoform demonstrating such an association. TS3 Asn347 CBG glycoform concentration <27.9 nmol/L was also associated with increased 28-day mortality (adj HR 2.2, 95% CI 1.1-4.4, p = 0.023), which was not the case with lowest tertile of total CBG concentration (<200 nmol/L). Conclusions Deficiency of the Asn347 TS3 CBG glycoform is associated with ICU and 28-day mortality in septic shock.