Differences in IgG Sialylation Distinguish Asymptomatic From Symptomatic Antinuclear Antibody-Positive Individuals
Carolina Muñoz-Grajales1, Carmen C Ucciferri2, Sindhu R Johnson3
1Department of Immunology, Faculty of Medicine, University of Toronto and Schroeder Arthritis Institute, Krembil Research Institute, University Health Network, Toronto, Ontario, and Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
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.
