Sialyltransferase and Neuraminidase Levels/Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study

PLOS ONE, Dec 2019

Objective 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). Methods 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. Results 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. Conclusion 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.

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Sialyltransferase and Neuraminidase Levels/Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study

March Sialyltransferase and Neuraminidase Levels/ Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study Lieh-bang Liou 0 1 Che-ching Huang 0 1 0 Editor: Jose Crispin, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran , MEXICO 1 Division of Rheumatology , Allergy, and Immunology , Chang Gung Memorial Hospital at Lin-kou, Kwei-san District, Tao-yuan City, Taiwan, 2 Chang Gung University College of Medicine , Kwei-san District, Tao-yuan City , Taiwan 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 α2,3-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. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by Chang Gung Medical Foundation, Taiwan and Ministry of Science and Technology, Taiwan, ROC (CMRPG3B0171 and NSC 102-2314-B-182A-093). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Objective Methods Results Conclusion 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. Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by polyclonal Bcell activation and the presence of many autoantibodies against a variety of autoantigens. The anti-dsDNA antibody is important in SLE and has long been used as a classification criterion and marker of disease activity, especially in lupus nephritis, though a study of clinical data [ 1 ] challenged the prognostic value of the anti-dsDNA antibody for disease flares. Most recently, the latter view is supported by an article that suggests that anti-dsDNA status does not seem to influence lupus disease activity [ 2 ]. Hence, elevated anti-dsDNA antibody with low complement levels have been used to monitor lupus activity for a long period of time, though their use is mainly restricted to predict outcome of lupus nephritis [ 3 ]. Nevertheless, a lot of articles on cytokines, chemokines, cell surface molecules, particular B-cell subsets, autoantibodies, and genetic (microRNAs) expression markers have been published to relate to lupus disease activity in the past 10 years [ 4–6 ]. The message is quite obvious: elevated anti-dsDNA antibody and/or low complement levels are not satisfactory enough for monitoring SLE disease activity in general and also for its diverse complications. In particular, lupus pathogenesis might also be affected by characteristics of B cells, by closely related immune cells (such as T cells and monocytes), or even by inflammatory cells such as polymorphonuclear (PMN) cells [ 7, 8 ]. Hence, immune cell abnormalities need also to be paid attention to. A 1989 report showed that the increase in IgG binding of guinea pig peritoneal macrophages after neuraminidase treatment (which eliminates cell-surface sialic acid [SIA]) was due to increased affinity and not the number of Fcγ receptors [ 9 ]. Later, it was found that sialylated N-glycans on the cell surface suppressed the induction of phagocytosis, and that decreased expression of sialylation results in acquisition of the phagocytic ability in mouse monocytic cells [ 10 ]. Moreover, tolerogenic, immature dendritic cells had a higher α-2,6-SIA level, which was drastically downregulated by pro-inflammatory cytoines once the dendritic cells matured [ 11 ]. These results imply (...truncated)


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Lieh-bang Liou, Che-ching Huang. Sialyltransferase and Neuraminidase Levels/Ratios and Sialic Acid Levels in Peripheral Blood B Cells Correlate with Measures of Disease Activity in Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis: A Pilot Study, PLOS ONE, 2016, Volume 11, Issue 3, DOI: 10.1371/journal.pone.0151669