Reverse expression of α2,6-sialic acid ratios on IgG/IgM and IgG/IgM autoantibodies correlates with mouse arthritis and rheumatoid arthritis disease activity.

BACKGROUND Sialic acids, e.g., α2,6-sialic acids (α2,6-SIAs), can link to conserved N-glycans of immunoglobulin G (IgG). In this study, we investigated the correlation between α2,6-SIA on IgG and IgM and the disease activity of arthritis and rheumatoid arthritis (RA) in mice. METHODS We measured α2,6-SIA levels in IgGs and IgMs in collagen-induced arthritis (CIA). Additionally, α2,6-SIA levels in rheumatoid factors (RFs) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA patients were measured. Correlations between α2,6-SIA on Igs and CIA were analyzed in RA patients by utilizing the disease activity score 28 (DAS28). The ability to differentiate RA progression by Ig and autoantibody α2,6-SIA levels was examined. RESULTS In CIA mice, plasma IgG-α2,6-SIA/IgG ratios decreased, whereas plasma IgM-α2,6-SIA/IgM ratios increased. Moreover, arthritis was not observed in collagen-injected mice with decreased IgG-α2,6-SIA/IgG ratios and without increased IgM-α2,6-SIA/IgM ratio. Isolated IgG-α2,6-SIA/IgG ratios displayed a significant inverse correlation with DAS28 scores (r =-0.383, p = 0.037). In contrast, isolated IgM-α2,6-SIA/IgM ratios correlated positively with DAS28 scores (r = 0.351, p = 0.009). Isolated IgG-anti-CCP-α2,6-SIA/ plasma IgG-anti-CCP ratios were differentiated into either the remission (higher ratios) or non-remission (lower ratios) category (p = 0.061), which is similar to the pattern for C-reactive protein (CRP) (p = 0.041), but different from that of the erythrocyte sedimentation rate (ESR) (p = 0.421). Using multiple linear regression analysis, plasma IgMRF-α2,6-SIA/IgMRF ratios displayed a correlation with DAS28 (p = 0.006), which was also observed in the ESR (p = 0.005), but was different from that for CRP (p = 0.222). CONCLUSION Concurrent reverse expression of α2,6-SIA ratios on IgM and IgG correlated with the occurrence of CIA and RA disease activity. Thus, α2,6-SIA ratios on IgG-anti-CCP antibodies and IgMRF are potential markers for evaluating RA disease activities.