Differences in IgG Sialylation Distinguish Asymptomatic From Symptomatic Antinuclear Antibody-Positive Individuals.

OBJECTIVE: The transition from asymptomatic antinuclear antibody (ANA) positivity to systemic autoimmune rheumatic disease (SARD) is associated with increased production of proinflammatory factors such as tumor necrosis factor α (TNFα). Here we investigate whether the relative absence of inflammation in asymptomatic ANA+ individuals (ANA+NS) results from a lack of circulating immune complexes (ICs) or from changes in the characteristics of the IgG autoantibodies produced.

METHODS: Flow cytometry was used to characterize circulating microparticles (MPs) in 18 healthy controls (ANA-HC), 31 ANA+NS, and 51 symptomatic ANA+ patients. Differences in the ability of the total MPs, purified IgG-coated MPs, or aggregated IgG to elicit inflammation were investigated by coculture with ANA-HC monocytes or monocyte-derived dendritic cells (moDCs), measuring cytokines in the supernatants. IgG sialylation was quantified by enzyme-linked immunosorbent assay or lectin blotting using Sambucus nigra agglutinin, a sialic acid-binding lectin.

RESULTS: All ANA+ individuals had higher numbers of total and IgG-coated MPs than ANA-HC. IgG sialylation was significantly reduced in individuals with SARD compared to ANA+NS and ANA-HC and in ANA+NS who clinically progressed in the next two years compared to those who did not. moDCs stimulated with IgG-coated MPs or aggregated IgG from patients with systemic lupus erythematosus produced significantly more TNFα than those from ANA+NS. The levels of TNFα produced in culture supernatants and serum demonstrated a negative correlation with IgG sialylation.

CONCLUSION: The absence of proinflammatory factors in ANA+NS does not result from a lack of circulating ICs but instead may reflect differences in the extent of IgG sialylation in the ICs from ANA+NS as compared to those with SARD.