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 (SIAs), for example, alpha 2,6-SIAs, can link to conserved N-glycans of immunoglobulin G (IgG). In this study, we investigated the correlation between alpha 2,6-SIA on IgG and IgM and the disease activity of arthritis and rheumatoid arthritis (RA) in mice. Methods: We measured alpha 2,6-SIA levels in IgGs and IgMs in collagen-induced arthritis (CIA). Additionally, alpha 2,6-SIA levels in rheumatoid factors (RFs) and anti-cyclic citrullinated peptide (anti-CCP) antibodies in RA patients were measured. Correlations between alpha 2,6-SIA on Igs and CIA were analyzed and also in RA patients by utilizing the disease activity score 28 (DAS28). The ability to differentiate RA progression by Ig and autoantibody alpha 2,6-SIA levels was examined. Results: In CIA mice, plasma IgG-alpha 2,6-SIA/IgG ratios decreased, whereas plasma IgM-alpha 2,6-SIA/IgM ratios increased. Moreover, arthritis was not observed in collagen-injected mice with decreased IgG-alpha 2,6-SIA/IgG ratios and without increased IgM-alpha 2,6-SIA/IgM ratios. Isolated IgG-alpha 2,6-SIA/IgG ratios displayed a significant inverse correlation with DAS28 scores (r = -0.383, p = 0.037). In contrast, isolated IgM-alpha 2,6-SIA/IgM ratios correlated positively with DAS28 (r = 0.351, p = 0.009). Isolated IgG-anti-CCP-alpha 2,6-SIA/plasma IgG-anti-CCP ratios were differentiated into either the remission (higher ratios) or the nonremission (lower ratios) category (p = 0.061), which is similar to the pattern for C-reactive protein (CRP) (p = 0.041) but different from that for the erythrocyte sedimentation rate (ESR) (p = 0.421). Using multiple linear regression analysis, plasma IgMRF-alpha 2,6-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 alpha 2,6-SIA ratios on IgM and IgG correlated with the occurrence of CIA and RA disease activity. Thus, alpha 2,6-SIA ratios on IgG-anti-CCP antibodies and IgMRF are potential markers for evaluating RA disease activities.