Rheumatoid arthritis (RA) is a chronic autoimmune disease for which prediction of long-term prognosis from disease’s outset is not clinically feasible. The importance of immunoglobulin G (IgG) and its Fc N-glycosylation in inflammation is well-known and studies described its relevance for several autoimmune diseases, including RA. Herein we assessed the association between IgG N-glycoforms and disease prognosis at 2 years in an early inflammatory arthritis cohort. Sera from 118 patients with early inflammatory arthritis naïve to treatment sampled at baseline were used to obtain IgG Fc glycopeptides, which were then analyzed in a subclass-specific manner by liquid chromatography coupled to mass spectrometry (LC-MS). Patients were prospectively followed and a favorable prognosis at 2 years was assessed by a combined index as remission or low disease activity (DAS28 < 3.2) and normal functionality (HAQ ≤ 0.25) while on treatment with conventional synthetic DMARDs and never used biologic DMARDs. We observed a significant association between high levels of IgG2/3 Fc galactosylation (effect 0.627 and adjusted p value 0.036 for the fully galactosylated glycoform H5N4F1; effect −0.551 and adjusted p value 0.04963 for the agalactosylated H3N4F1) and favorable outcome after 2 years of treatment. The inclusion of IgG glycoprofiling in a multivariate analysis to predict the outcome (with HAQ, DAS28, RF, and ACPA included in the model) did not improve the prognostic performance of the model. Pending confirmation of these findings in larger cohorts, IgG glycosylation levels could be used as a prognostic marker in early arthritis, to overcome the limitations of the current prognostic tools.

中文翻译：

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基线 IgG-Fc N-糖基化谱与一组早期炎症性关节炎患者的长期结果相关

类风湿性关节炎 (RA) 是一种慢性自身免疫性疾病，从疾病开始就预测其长期预后在临床上是不可行的。免疫球蛋白 G (IgG) 及其 Fc N-糖基化在炎症中的重要性是众所周知的，研究描述了它与包括 RA 在内的几种自身免疫性疾病的相关性。在此，我们评估了早期炎症性关节炎队列中 IgG N-糖型与 2 年疾病预后之间的关联。来自 118 名早期炎症性关节炎患者的血清在基线时采样，用于获得 IgG Fc 糖肽，然后通过液相色谱与质谱联用 (LC-MS) 以亚类特异性方式对其进行分析。对患者进行前瞻性随访，在接受常规合成 DMARD 治疗且从未使用过生物 DMARD 时，通过综合指数评估疾病活动度缓解或低（DAS28 < 3.2）和功能正常（HAQ ≤ 0.25）来评估患者的良好预后。我们观察到高水平的 IgG2/3 Fc 半乳糖基化（完全半乳糖基化糖型 H5N4F1 的影响为 0.627 和调整后的 p 值 0.036；半乳糖基化的 H3N4F1 的影响 -0.551 和调整后的 p 值 0.04963）与治疗 2 年后的良好结果之间存在显着关联. 将 IgG 糖谱分析纳入多变量分析以预测结果（模型中包含 HAQ、DAS28、RF 和 ACPA）并未改善模型的预后性能。在更大的队列中确认这些发现之前，