Figure 5.

Galactosylation of total immunoglobulin G (IgG) affects IgG-occupation of FcγRIIIa, affecting activation thresholds and flares in autoimmunity. In autoimmune diseases, such as rheumatoid arthritis, disease severity is negatively correlated with the degree of galactosylation. Galactosylation of IgG is important for binding to FcγRIIIa, where—in combination with afucosylation—a higher degree of IgG-Fc galactosylation increases the affinity. Only ~6% of normal serum IgGs is afucosylated. During remission (left), the total IgG galactosylation is relatively high, which prevents autoantibodies to engage the FcγRs. During a flare of disease (right), the total IgG galactosylation is low, which reduces the overall binding affinity of total IgG to FcγRIII, and therefore lowers the threshold for FcγR-activation by allowing more easy access by pathogenic autoantibodies, causing immune activation (green lightning bolt).