Remodeling of Anti-Carbohydrate Antibody Repertoires in Critical Illness Identifies Anti-αGal Signatures Associated with Secondary Infection

Anti-carbohydrate antibodies (ACA) are key components of natural humoral immunity, yet their regulation during critical illness remains poorly understood. We profiled ACA against 585 glycans in ICU patients (n=91) and healthy controls (n=39) using longitudinal sampling and a printed glycan array, and quantified anti-Galα1-3Galβ1-4GlcNAc (αGal) antibody isotypes by ELISA. ICU patients showed broadly reduced ACA reactivity compared with healthy controls. While ACA profiles at ICU admission were not associated with diagnosis or mortality, patients who developed ICU-acquired infections exhibited longitudinal remodeling of α-galactosyl antibody repertoires, particularly anti-αGal and anti-blood group B responses. Higher anti-αGal IgM and IgG3 levels at ICU admission were associated with subsequent ICU-acquired infection, and these patients also demonstrated longitudinal increases in anti-αGal IgM during ICU stay. These findings identify dynamic remodeling of α-galactosyl natural antibody networks during ICU-acquired infection and support anti-αGal antibodies, particularly IgM, as candidate biomarkers and potential targets for modulation in critical illness.