Differences in IgG Sialylation Distinguish Asymptomatic from Symptomatic Anti-Nuclear Antibody Positive Individuals.

Objective: The transition from asymptomatic anti-nuclear antibody (ANA) positivity to systemic autoimmune rheumatic disease (SARD) is associated with increased production of pro-inflamamtory factors such as TNF-α. Here we investigate whether the relative absence of inflammation in asymptomatic ANA individuals (ANANS) results from a lack of circulating immune complexes (ICs) or from changes in the characteristics of the IgG auto-Abs produced.

Methods: Flow cytometry was used to characterize circulating microparticles (MPs) in 18 healthy controls (ANAHC), 31 ANANS 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 co-culture with ANAHC monocytes or monocyte derived dendritic cells (moDC), measuring cytokines in the supernatants. IgG sialylation was quantified by ELISA 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 ANAHC. IgG sialylation was significantly reduced in SARD compared to ANANS and ANAHC, and in ANANS who clinically progressed in the next 2 years compared to those who did not. moDC stimulated with IgG-coated MPs or aggregated IgG from SLE patients produced significantly more TNF-α than those from ANANS. The levels of TNF-α produced in culture supernatants and serum demonstrated a negative correlation with IgG sialylation.

Conclusions: The absence of pro-inflammatory factors in ANANS does not result from a lack of circulating ICs, but instead may reflect differences in the extent of IgG sialylation in the ICs from ANANS as compared to SARD.