Liou Lieh-Bang, Tsai Ping-Han, Fang Yao-Fan, Chen Yen-Fu, Chang Che-Tzu, Chen Chih-Chieh, Chiang Wen-Yu
Division of Rheumatology, Allergy and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei 236017, Taiwan.
Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital at Linkou, Taoyuan 333423, Taiwan.
Int J Mol Sci. 2025 Aug 25;26(17):8226. doi: 10.3390/ijms26178226.
The associations between sialylated anti-cyclic citrullinated peptide (anti-CCP) antibodies bearing α-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 α-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 (ρ = -0.317 with = 0.013. Plasma (free-form) Neu1 levels were inversely correlated with SIA/IgG anti-CCP ratios (ρ = -0.361, = 0.001) in the DAS28-MCP-1 < 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 ≤ 11 and DAS28-MCP-1 ≤ 3.6 combined remission and low-disease-activity subgroups (ρ = -0.315 with = 0.001 and ρ = -0.237 with = 0.008, respectively). The same was observed for B-cell ST6Gal1/Neu1 ratios correlating with the SDAI ≤ 11 subgroup (ρ = -0.261, = 0.009). Nevertheless, B-cell ST6Gal1/Neu1 ratios against SDAI ≤ 11 and DAS28-MCP-1 ≤ 3.6 subgroups produced significant area-under-curve (AUC) values of 0.616 and 0.600, respectively (asymptotic -Values 0.004 and 0.018, respectively). Through multivariate regression analyses, we found that biologics (a confounding factor) interfered with -Values related to the B-cell ST6Gal1 enzyme but did not interfere with -Values related to the pure B-cell Neu1 enzyme. In addition, disease duration interfered with -Values related to the pure Neu1 enzyme on B-cells or in plasma. Moreover, plasma ST6Gal1/Neu1 ratios against the DAS28-MCP-1 < 2.2 remission subgroup produced an AUC of 0.628 and asymptotic = 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.
在类风湿关节炎（RA）中，携带α-2,6-唾液酸（SIA）的唾液酸化抗环瓜氨酸肽（抗CCP）抗体、ST6Gal1和Neu1酶与疾病活动度的临床指标（如疾病活动评分28（DAS28）、简化疾病活动指数（SDAI）和临床疾病活动指数（CDAI））之间的关联尚不清楚。为填补这一空白，本研究纳入了97例RA患者，在基线（第0个月）以及第6和12个月进行评估。每次就诊时，分析血细胞中B细胞ST6Gal1和Neu1的表达，并评估血浆样本中ST6Gal1和Neu1的水平。检测红细胞沉降率（ESR）、C反应蛋白（CRP）、单核细胞趋化蛋白-1（MCP-1）以及带有α-2,6-SIA修饰的IgG抗CCP。计算疾病活动指标，即DAS28-ESR、DAS28-CRP、DAS28-MCP-1、SDAI和CDAI。评估ST6Gal、Neu1、SIA/抗CCP比值与疾病活动指标之间的相关性和受试者工作特征。进行多变量回归分析以揭示此类相关性中的混杂因素。抗CCP抗体的总SIA含量与B细胞Neu1水平呈负相关（ρ = -0.317，P = 0.013）。在DAS28-MCP-1 < 2.2（缓解）亚组中，血浆（游离形式）Neu1水平与SIA/IgG抗CCP比值呈负相关（ρ = -0.361，P = 0.001）。在DAS28-ESR、DAS28-CRP、SDAI或CDAI亚组中未观察到此类相关性。B细胞ST6Gal1水平与SDAI≤11以及DAS28-MCP-1≤3.6的联合缓解和低疾病活动亚组呈负相关（分别为ρ = -0.315，P = 0.001和ρ = -0.237，P = 0.008）。B细胞ST6Gal1/Neu1比值与SDAI≤11亚组也有相同情况（ρ = -0.261，P = 0.009）。然而，针对SDAI≤11和DAS28-MCP-1≤3.6亚组的B细胞ST6Gal1/Neu1比值产生的曲线下面积（AUC）值分别为0.616和0.600（渐近P值分别为0.004和0.018）。通过多变量回归分析，我们发现生物制剂（一个混杂因素）干扰了与B细胞ST6Gal1酶相关的P值，但未干扰与纯B细胞Neu1酶相关的P值。此外，病程干扰了与B细胞或血浆中纯Neu1酶相关的P值。而且，针对DAS28-MCP-1 < 2.2缓解亚组的血浆ST6Gal1/Neu1比值产生的AUC为0.628，渐近P = 0.003。因此，提示B细胞ST6Gal1/Neu1比值可作为SDAI和DAS28-MCP-1公式联合缓解和低疾病活动亚组的临床指标。血浆ST6Gal1/Neu1比值也是DAS28-MCP-1缓解的良好指标。
