We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect. In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1. Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r = 0.984, P<0.001) and DAS28-CRP (r = 0.971, P<0.001), and modestly correlated with CRP (r = 0.350, P<0.001), and ESR (r = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r = 0.944, P<0.001; r = 0.951, P<0.001; r = 0.862, P<0.001; and r = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively). Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.

This prospective one-year follow-up study was conducted from 835 visits in 178 rheumatoid arthritis (RA) patients. Tender-/swollen-joint count, Health Assessment Questionnaire Disability Index (HAQ-DI), Disease Activity Score 28-ESR (DAS28-ESR), DAS28-CRP, Simplified Disease Activity Index (SDAI) and DAS28-monocyte chemotactic protein-1 (DAS28-MCP-1) scores were obtained every 3 months. Radiographs of hands and feet were acquired at baseline and one year. We evaluated the correlation and accuracy of activity scores in predicting remission, HAQ-DI changes and radiographic changes. DAS28-MCP-1 correlated strongly with DAS28-ESR, DAS28-CRP and SDAI scores (0.830, 0.899 and 0.931, respectively, with all P < 0.001). Score changes of DAS28-MCP-1 were comparable to those of DAS28-ESR, DAS28-CRP and SDAI in predicting changes in HAQ-DI and bone erosion. DAS28-MCP-1 (<2.2) was better than DAS28-ESR (<2.6) in indicating modified American Rheumatism Association remission and 2011 American College of Rheumatology/European League Against Rheumatism remission (75.61% vs. 36.99% and 81.71% vs. 49.13%, respectively) with odds ratios of 5.28 and 4.62 (both P < 0.001), respectively. We compared DAS28-MCP-1 with SDAI (≦3.3) in indicating remission with odds ratios of 2.63 (P = 0.002) and 0.98, respectively (and DAS28-MCP-1 with DAS28-CRP < 2.5: 1.33 and 0.92). Therefore, DAS28-MCP-1 is useful as an alternative in assessing RA activity.

We attempted to determine whether the level of enzymes sialyltransferase (ST) and neuraminidase (Neu) and sialic acid (SIA) in patients with systemic lupus erythematosus (SLE) correlates with the SLE Disease Activity Index (SLEDAI) and in patients with rheumatoid arthritis (RA) correlates with the Disease Activity Score28 (DAS28). We examined cell-surface levels of ST6Gal-1, Neu1, ST3Gal-1, Neu3, α-2,6-SIA, and α-2,3-SIA by using fluorescent anti-enzyme antibodies, fluorescent-conjugated Sambucus nigra lectin, and fluorescent-conjugated Maackia amurensis lectin on blood cells in SLE and RA patients and assessed correlations of these levels with SLEDAI and with DAS28. Areas under the curve (AUC) were calculated for different variables against SLEDAI. The B-cell ST3Gal-1/Neu3 ratio positively correlated with SLEDAI scores (ρ = 0.409 and P = 0.002, statistically significant after Bonferroni’ correction for multiple analyses.). It was supported by the inverse correlation of B-cell Neu3 levels with SLEDAI scores (ρ = −0.264, P = 0.048). The B-cell ST3Gal-1/Neu3 ratio against SLEDAI yielded an AUC of 0.689, which was comparable to that of anti-dsDNA levels at 0.635. In contrast, both ST3Gal-1 and Neu3 levels of RA B cells (r = 0.376, P = 0.013; r = 0.425, P = 0.005, respectively) correlated positively with high disease-activity DAS28 scores. B-cell ST3Gal-1/Neu3 ratios in SLE and B-cell ST3Gal-1 and Neu3 levels in RA with high disease-activity DAS28 scores correlated with disease activity measures and may be useful in monitoring disease activities.

Background: Sialic acids (SIAs), for example, 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 and also 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 ratios. 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 (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 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-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.

We studied the association of monocyte α-2,3-sialyltransferase 1 (ST3Gal-1), neuraminidase-3 (Neu3), α-2,6-sialyltransferase 1 (ST6Gal-1), and neuraminidase-1 (Neu1) levels with disease activity score 28 (DAS28) in human rheumatoid arthritis (RA), considering that mouse monocytes’ sialic acid levels related to their phagocytosis and IgG binding ability. ST3Gal-1, Neu3, ST6Gal-1, Neu1, α-2,3-sialic acid, and α-2,6-sialic acid levels on RA peripheral blood monocytes, T cells, and polymorphonuclear cells were determined by using fluorochrome-conjugated anti-cell-specific-marker antibodies and fluorochrome-conjugated anti-enzyme antibodies. Simple correlation and linear regression were used to correlate enzyme levels with DAS28. RA monocyte ST3Gal-1 and Neu3 levels correlated with DAS28 in patients having DAS28 greater than 5.1 (r = 0.469, p = 0.002; r = 0.410, p = 0.006, respectively). When multivariable analysis was performed for erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and sialic acid-related enzyme levels in different cell types as independent variables with DAS28 as a dependent variable, monocyte ST3Gal-1 levels correlated with DAS28 (p = 0.009) but not ESR and CRP in patients having DAS28 greater than 5.1 (both P ≥ 0.292). RA monocyte ST3Gal-1 levels correlated with DAS28 (p = 0.010) and with ESR (p < 0.001) at month 0 when applied to all RA patients including both remission and non-remission groups in multivariable analysis. The latter findings persisted longitudinally at month 3. Monocyte ST3Gal-1 and Neu3 levels correlated longitudinally with DAS28 by two different methods suggests that monocyte ST3Gal-1 and Neu3 levels may be used as biomarkers to monitor RA disease activity. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).