Immunoglobulin G and plasma glycome in early rheumatoid arthritis differ from matched controls and link less fat-free mass to an accelerated aging phenotype: an exploratory study

In patients with rheumatoid arthritis (RA), the immunoglobulin G (IgG) glycome is altered and characterized by decreased galactosylation. The goals of our exploratory study were to identify (1) alterations in the IgG and plasma glycome and GlycanAge—a glycome-based biological age measure—in patients with early RA and (2) changes in the RA glycome following a lifestyle intervention. IgG and plasma glycome and clinical and physiological parameters were analyzed from two cohorts: (1) participants with early RA (symptom duration < 6 months; n = 10) and age-, sex- and BMI-matched healthy controls (n = 10); and (2) older participants (age > 60) with RA (n = 20) who completed a diet and exercise intervention. As compared to controls (chronologic age = 53.2 ± 12.3 years), early RA (chronologic age = 53.6 ± 12.9 years) had a GlycanAge corresponding to 18.1 years older (42.1 ± 25.3 versus 60.2 ± 19.5 years; p = 0.03), greater plasma tetra-galactosylated, tri-sialylated, tetra-sialylated, and antennary fucosylated glycans, and lesser plasma mono-sialylated and oligomannan glycans (p < 0.05 for all). Controlling for chronologic age and sex, RA (n = 39) GlycanAge was negatively associated with cardiorespiratory fitness (V̇O2 peak, mL/kg/min; beta=-1.66, p = 0.005) and fat-free mass (kg; beta=-1.77, p = 0.004). While a diet and exercise lifestyle intervention for RA (n = 20) did not significantly alter glycome parameters, reductions in GlycanAge were associated with increases in fat-free mass (Spearman rho=-0.46, p = 0.04). Changes in the RA glycome occur early in the RA disease process and may be useful as biomarkers for RA diagnosis and monitoring. Further study is needed to explore the potential for lifestyle interventions targeting improvements in cardiorespiratory fitness and body composition to impact the glycome and accelerated biological aging linked to RA. ClinicalTrials.gov, NCT04226131, registered on January 13, 2020 NCT04356183, registered on April 22, 2020.