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首页> 外文期刊>EBioMedicine >Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis
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Galactosylation and Sialylation Levels of IgG Predict Relapse in Patients With PR3-ANCA Associated Vasculitis

机译：PR3-ANCA相关性血管炎患者的半乳糖基化和IgG唾液酸化水平预测复发

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Objective: The objective of our study is to investigate the Fc glycosylation profiles of both antigen-specific IgG targeted against proteinase 3 (PR3-ANCA) and total IgG as prognostic markers of relapse in patients with Granulomatosis with Polyangiitis (GPA). Methods: Seventy-five patients with GPA and a PR3-ANCA rise during follow-up were included, of whom 43 patients relapsed within a median period of 8 (2-16) months. The N-glycan at Asn297 of affinity-purified and denatured total IgG and PR3-ANCA was determined by mass spectrometry of glycopeptides in samples obtained at the time of the PR3-ANCA rise and at the time of the relapse or time-matched during remission. Results: Patients with total IgG1 exhibiting low galactosylation or low sialylation were highly prone to relapse after an ANCA rise (HR 3.46 [95%-CI 1.73-6.96], p<0.0001 and HR 3.22 [95%-CI 1.52-6.83], p=0.002, respectively). In relapsing patients, total IgG1 galactosylation, sialylation and bisection significantly decreased and fucosylation significantly increased from the time of the PR3-ANCA rise to the relapse (p<0.0001, p=0.0087, p<0.0001 and p=0.0025), while the glycosylation profile remained similar in non-relapsing patients. PR3-ANCA IgG1 galactosylation, sialylation and fucosylation of PR3-ANCA IgG1 decreased in relapsing patients (p=0.0073, p=0.0049 and p=0.0205), but also in non-relapsing patients (p=0.0007, p=0.0114 and p=0.0002), while bisection increased only in non-relapsing patients (p<0.0001). Conclusion: While Fc glycosylation profiles have been associated with clinically manifest autoimmune diseases, in the present study we show that low galactosylation and sialyation in total IgG1 but not PR3-ANCA IgG1 predicts disease reactivation in patients with GPA who experience an ANCA rise during follow-up. We postulate that glycosylation profiles may be useful in pre-emptive therapy studies using ANCA rises as guideline.
机译：目的：我们的研究目的是研究针对蛋白酶3（PR3-ANCA）的抗原特异性IgG和总IgG作为多发性肉芽肿性多血管炎（GPA）患者复发的预后标志物的Fc糖基化谱。方法：纳入75例GPA且随访期间PR3-ANCA升高的患者，其中43例在中位8（2-16）个月内复发。亲和纯化和变性的总IgG和PR3-ANCA的Asn297处的N-聚糖是通过在PR3-ANCA升高时，复发时或缓解期间时间匹配的样品中糖肽的质谱测定的。结果：ANCA升高后，总IgG1表现出低半乳糖基化或低唾液酸化的患者极易复发（HR 3.46 [95％-CI 1.73-6.96]，p <0.0001和HR 3.22 [95％-CI 1.52-6.83]， p = 0.002）。在复发患者中，从PR3-ANCA升高到复发，总IgG1半乳糖基化，唾液酸化和二等分明显减少，岩藻糖基化显着增加（p <0.0001，p = 0.0087，p <0.0001和p = 0.0025），而糖基化非复发性患者的病情特征仍然相似。 PR3-ANCA IgG1的半乳糖基化，唾液酸化和岩藻糖基化的PR3-ANCA IgG1在复发患者中降低（p = 0.0073，p = 0.0049和p = 0.0205），但在非复发患者中也降低（p = 0.0007，p = 0.0114和p = 0.0002），而平分仅在非复发性患者中增加（p <0.0001）。结论：尽管Fc糖基化谱已与临床上显示的自身免疫性疾病相关，但在本研究中，我们显示总IgG1中的半乳糖基化和唾液酸化程度低，但PR3-ANCA IgG1中的低半乳糖基化和唾液酸化预示了在随访期间经历ANCA升高的GPA患者的疾病重新活化向上。我们假设糖基化谱可能在以ANCA作为指导的先发疗法研究中有用。

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