Work

Determinants of Immunoglobulin‐G N‐Glycan Patterns in the Aging General Population

Year: 2026

Type: article

Abstract: ABSTRACT Background N ‐glycosylation drives immunoglobulin G (IgG) stability and function, directly affecting immune response. However, the effect of demographic and modifiable lifestyle factors on IgG N ‐glycosylation in the general population remains poorly characterized. Methods This study investigated the effects of age, sex, smoking, alcohol, body mass index (BMI), and time on IgG Fc N ‐glycosylation patterns in the population‐based Rotterdam Study. IgG1–4 compositions were quantified by nanoflow liquid chromatography–electrospray ionization–mass spectrometry (nano–LC–ESI–MS) and expressed as percentages of the total signal. Cross‐sectional associations were assessed using the confounder‐adjusted multiple linear regression, while longitudinal changes were evaluated using the mixed effects models. Results This study included 8242 participants (mean age = 64.2 years) with repeated measurements for 448 participants (mean follow‐up = 5.6 years). Age and BMI were associated with increased bisection and fucosylation (β = 0.007–0.030 SD/unit increase) and decreased galactosylation and sialylation (β = −0.007 to −0.057 SD). Women demonstrated higher bisection (β = 0.102–0.329 SD) across all subclasses, lower galactosylation, and sialylation in IgG 1 ‐ 3 (β = −0.042 to −0.138 SD), but higher levels in IgG 4 (β = 0.062–0.070 SD), and pronounced changes between 45 to 55 years. Smoking (β = 0.621 to 0.825 SD) and alcohol were associated with increased bisection, with a gradient effect in smoking status. With time, galactosylation and sialylation declined (β = −0.055 to −0.087 SD/year), while bisection increased (β = 0.030 to 0.050 SD/year). Conclusion Aging, higher BMI, female sex, smoking, and heavy alcohol consumption are key determinants of IgG N ‐glycome patterns, which are indicative of inflammation. Over time, glycan compositions demonstrate a gradual change toward a pro‐inflammatory phenotype in a sex‐related manner.

Source: Allergy

DOI: 10.1111/all.70361