{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:15:36Z","timestamp":1789820136188,"version":"4.0.1"},"reference-count":21,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Medical Foundation, Taiwan","award":["CMRPVVL0202"],"award-info":[{"award-number":["CMRPVVL0202"]}]},{"name":"Chang Gung Medical Foundation, Taiwan","award":["CMRPVVN0162"],"award-info":[{"award-number":["CMRPVVN0162"]}]},{"name":"Chang Gung Medical Foundation, Taiwan","award":["CMRPG3N1191"],"award-info":[{"award-number":["CMRPG3N1191"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The associations between sialylated anti-cyclic citrullinated peptide (anti-CCP) antibodies bearing \u03b1-2,6-sialic acid (SIA), ST6Gal1 and Neu1 enzymes, and clinical disease activity measures such as disease activity score 28 (DAS28), the Simplified Disease Activity Index (SDAI), and Clinical Disease Activity Index (CDAI) are unknown in rheumatoid arthritis (RA). To address this gap, this study included 97 patients with RA evaluated at baseline (month 0) and at 6 and 12 months. At each visit, blood cells were analyzed for B-cell ST6Gal1 and Neu1 expressions, and plasma samples were assessed for ST6Gal1 and Neu1 levels. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), monocyte chemotactic protein-1 (MCP-1), and IgG anti-CCP with its \u03b1-2,6-SIA modification were measured. Disease activity measures, namely DAS28-ESR, DAS28-CRP, DAS28-MCP-1, SDAI, and CDAI, were calculated. Correlations and Receiver Operating Characteristics among ST6Gal, Neu1, SIA\/anti-CCP ratios, and disease activity measures were assessed. Multivariate regression analyses were performed to reveal confounding factors in such correlations. The total SIA content of anti-CCP antibodies was inversely correlated with B-cell Neu1 levels (\u03c1 = \u22120.317 with p = 0.013. Plasma (free-form) Neu1 levels were inversely correlated with SIA\/IgG anti-CCP ratios (\u03c1 = \u22120.361, p = 0.001) in the DAS28-MCP-1 &lt; 2.2 (remission) subgroup. No such correlation was observed for the DAS28-ESR, DAS28-CRP, SDAI, or CDAI subgroups. B-cell ST6Gal1 levels correlated inversely with SDAI \u2264 11 and DAS28-MCP-1 \u2264 3.6 combined remission and low-disease-activity subgroups (\u03c1 = \u22120.315 with p = 0.001 and \u03c1 = \u22120.237 with p = 0.008, respectively). The same was observed for B-cell ST6Gal1\/Neu1 ratios correlating with the SDAI \u2264 11 subgroup (\u03c1 = \u22120.261, p = 0.009). Nevertheless, B-cell ST6Gal1\/Neu1 ratios against SDAI \u2264 11 and DAS28-MCP-1 \u2264 3.6 subgroups produced significant area-under-curve (AUC) values of 0.616 and 0.600, respectively (asymptotic p-Values 0.004 and 0.018, respectively). Through multivariate regression analyses, we found that biologics (a confounding factor) interfered with p-Values related to the B-cell ST6Gal1 enzyme but did not interfere with p-Values related to the pure B-cell Neu1 enzyme. In addition, disease duration interfered with p-Values related to the pure Neu1 enzyme on B-cells or in plasma. Moreover, plasma ST6Gal1\/Neu1 ratios against the DAS28-MCP-1 &lt; 2.2 remission subgroup produced an AUC of 0.628 and asymptotic p = 0.003. Therefore, it is suggested that B-cell ST6Gal1\/Neu1 ratios can be used as clinical indicators for the combined remission and low-disease-activity subgroup of SDAI and DAS28-MCP-1 formulae. Plasma ST6Gal1\/Neu1 ratios are also good indicators of DAS28-MCP-1 remission.<\/jats:p>","DOI":"10.3390\/ijms26178226","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T06:08:37Z","timestamp":1756102117000},"page":"8226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["B-Cell ST6Gal1\/Neuraminidase 1 Ratios Inversely Predict the Combined Remission and Low-Disease-Activity Subgroup with DAS28-MCP-1 and SDAI Scores for Rheumatoid Arthritis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-5405","authenticated-orcid":false,"given":"Lieh-Bang","family":"Liou","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei 236017, Taiwan"},{"name":"Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"},{"name":"School of Medicine, Chang Gung University College of Medicine, Taoyuan 333323, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8134-9022","authenticated-orcid":false,"given":"Ping-Han","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei 236017, Taiwan"},{"name":"Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Fan","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Che-Tzu","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Chieh","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei 236017, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Yu","family":"Chiang","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Allergy and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei 236017, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0300-9084(01)01301-3","article-title":"The human sialyltransferases family","volume":"83","author":"Julien","year":"2001","journal-title":"Biochimie"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s10719-009-9260-y","article-title":"Transcriptional regulation of the human ST6GAL2 gene in cerebral cortex and neuronal cells","volume":"27","author":"Cazet","year":"2010","journal-title":"Glycoconj. J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9705","DOI":"10.1021\/bi901430h","article-title":"Branch Specific Sialylation of IgG-Fc Glycans by ST6Gal-I","volume":"48","author":"Barb","year":"2009","journal-title":"Biochemistry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1046\/j.1365-3083.2000.00692.x","article-title":"Enhanced sialyltransferase activity in B lymphocytes from patients with primary Sj\u00f6gren\u2019s syndrome","volume":"51","author":"Basset","year":"2000","journal-title":"Scand. J. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3070","DOI":"10.4049\/jimmunol.158.7.3070","article-title":"The control of IL-4 gene expression in activated murine T lymphocytes: A novel role for neu-1 sialidase","volume":"158","author":"Chen","year":"1997","journal-title":"J. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1074\/jbc.M109.055475","article-title":"Regulation of phagocytosis in macrophages by neuraminidase 1","volume":"285","author":"Seyrantepe","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/0165-2478(94)90214-3","article-title":"Roles of beta-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation-primed activation of macrophages","volume":"43","author":"Naraparaju","year":"1994","journal-title":"Immunol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"26252","DOI":"10.1074\/jbc.M110515200","article-title":"A close association of the ganglioside-specific sialidase Neu3 with caveolin in membrane microdomains","volume":"277","author":"Wang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1136\/ard.2005.037333","article-title":"Is DAS28 an appropriate tool to assess remission in rheumatoid arthritis?","volume":"64","author":"Makinen","year":"2005","journal-title":"Ann. Rheum. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/art.30129","article-title":"American College of Rheumatology\/European League against Rheumatism provisional definition of remission in rheumatoid arthritis for clinical trials","volume":"63","author":"Felson","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Liou, L.B., Tsai, P.H., Fang, Y.F., Chen, Y.F., Chen, C.C., and Lai, J.H. (2023). Sialic-acid-related enzymes of B cells and monocytes as novel markers to discriminate improvement categories and to fulfill two remission definitions in rheumatoid arthritis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612998"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11205","DOI":"10.1038\/ncomms11205","article-title":"Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis","volume":"7","author":"Ohmi","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1097\/JCMA.0000000000000439","article-title":"Reverse expression of \u03b12,6-sialic acid ratios on IgG, IgM, and IgG\/IgM autoantibodies correlates with mouse arthritis and rheumatoid arthritis disease activity","volume":"83","author":"Liou","year":"2020","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Liou, L.B., Fang, Y.F., Tan, C.F., Lai, J.H., Jang, S.S., Tsai, P.H., and Yeh, T.C. (2020). A new laboratory surrogate (Monocyte Chemotactic Protein-1) for Disease Activity Score28: A favourable indicator for remission in rheumatoid arthritis. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-65127-5"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"7207","DOI":"10.1073\/pnas.1523968113","article-title":"B-cell-independent sialylation of IgG","volume":"113","author":"Jones","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","first-page":"803","article-title":"ST6Gal1 in plasma is dispensable for IgG sialylation","volume":"32","author":"Oswald","year":"2022","journal-title":"Glycobiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41397-023-00302-1","article-title":"Non-steroidal anti-inflammatory drug target gene associations with major depressive disorders: A Mendelian randomization study integrating GWAAS, eQTL and mQTL Data","volume":"23","author":"He","year":"2023","journal-title":"Pharmocagenom. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1002\/art.27414","article-title":"Glycan Profiling of Anti\u2013Citrullinated Protein Antibodies Isolated From Human Serum and Synovial Fluid","volume":"62","author":"Scherer","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Gyebrovszki, B., \u00c1cs, A., Szab\u00f3, D., Auer, F., Novoz\u00e1nszki, S., Rojkovich, B., Magyar, A., Hudecz, F., V\u00e9key, K., and Drahos, L. (2022). The Role of IgG Fc Region N-Glycosylation in the Pathomechanism of Rheumatoid Arthritis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105828"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Liou, L.B., and Huang, C.C. (2016). 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, 11.","DOI":"10.1371\/journal.pone.0151669"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Liou, L.B., Fang, Y.F., Tsai, P.H., Chen, Y.F., Chang, C.T., Chen, C.C., and Chiang, W.Y. (2024). Immunoregulatory cells and cytokines discriminate Disease Activity Score 28-remission statuses and ultrasound grades in rheumatoid arthritis patients with non-high disease activity. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25168694"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:35:26Z","timestamp":1760034926000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/17\/8226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,25]]},"references-count":21,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["ijms26178226"],"URL":"https:\/\/doi.org\/10.3390\/ijms26178226","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,25]]}}}