Background and Aims

Causes of inflammatory bowel diseases are not well understood and the most prominent forms, Crohn’s disease (CD) and ulcerative colitis (UC), are sometimes hard to distinguish. Glycosylation of IgG has been associated with CD and UC. IgG Fc-glycosylation affects IgG effector functions. We evaluated changes in IgG Fc-glycosylation associated with UC and CD, as well as with disease characteristics in different patient groups.

Methods

We analyzed 3441 plasma samples obtained from 2 independent cohorts of patients with CD (874 patients from Italy and 391 from the United States) or UC (1056 from Italy and 253 from the US and healthy individuals [controls]; 427 in Italy and 440 from the United States). IgG Fc-glycosylation (tryptic glycopeptides) was analyzed by liquid chromatography coupled to mass spectrometry. We analyzed associations between disease status (UC vs controls, CD vs controls, and UC vs CD) and glycopeptide traits, and associations between clinical characteristics and glycopeptide traits, using a logistic regression model with age and sex included as covariates.

Results

Patients with CD or UC had lower levels of IgG galactosylation than controls. For example, the odds ratio (OR) for IgG1 galactosylation in patients with CD was 0.59 (95% confidence interval [CI], 0.51–0.69) and for patients with UC was 0.81 (95% CI, 0.71–0.92). Fucosylation of IgG was increased in patients with CD vs controls (for IgG1: OR, 1.27; 95% CI, 1.12–1.44), but decreased in patients with UC vs controls (for IgG23: OR, 0.72; 95% CI, 0.63–0.82). Decreased galactosylation associated with more severe CD or UC, including the need for surgery in patients with UC vs controls (for IgG1: OR, 0.69; 95% CI, 0.54–0.89) and in patients with CD vs controls (for IgG23: OR, 0.78; 95% CI, 0.66–0.91).

Conclusions

In a retrospective analysis of plasma samples from patients with CD or UC, we associated levels of IgG Fc-glycosylation with disease (compared to controls) and its clinical features. These findings could increase our understanding of mechanisms of CD and UC pathogenesis and be used to develop diagnostics or guide treatment.

中文翻译：

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免疫球蛋白 G 的糖基化与炎症性肠病的临床特征相关

 背景和目标

炎症性肠病的病因尚不清楚，其中最常见的形式克罗恩病 (CD) 和溃疡性结肠炎 (UC) 有时很难区分。 IgG 的糖基化与 CD 和 UC 相关。 IgG Fc 糖基化影响 IgG 效应子功能。我们评估了与 UC 和 CD 相关的 IgG Fc 糖基化变化，以及不同患者组的疾病特征。

 方法

我们分析了 3441 份血浆样本，这些样本取自 2 个独立的 CD 患者组（874 名患者来自意大利，391 名患者来自美国）或 UC 患者（1056 名患者来自意大利，253 名来自美国和健康个体[对照]；427 名来自意大利，440 名来自美国）。美国）。通过液相色谱与质谱联用分析 IgG Fc 糖基化（胰蛋白酶糖肽）。我们使用以年龄和性别作为协变量的逻辑回归模型，分析了疾病状态（UC 与对照、CD 与对照、UC 与 CD）与糖肽特征之间的关联，以及临床特征与糖肽特征之间的关联。

 结果

CD 或 UC 患者的 IgG 半乳糖基化水平低于对照组。例如，CD 患者 IgG1 半乳糖基化的比值比 (OR) 为 0.59（95% 置信区间 [CI]，0.51–0.69），UC 患者为 0.81（95% CI，0.71–0.92）。与对照组相比，CD 患者的 IgG 岩藻糖基化增加（IgG1：OR，1.27；95% CI，1.12–1.44），但与对照组相比，UC 患者的岩藻糖基化降低（IgG23：OR，0.72；95% CI，0.63– 0.82）。半乳糖基化降低与更严重的 CD 或 UC 相关，包括 UC 患者与对照患者相比需要手术（对于 IgG1：OR，0.69；95% CI，0.54–0.89）以及 CD 患者与对照患者相比（对于 IgG23：OR， 0.78；95% CI，0.66-0.91）。

 结论

在对 CD 或 UC 患者血浆样本的回顾性分析中，我们将 IgG Fc 糖基化水平与疾病（与对照相比）及其临床特征相关联。这些发现可以增加我们对 CD 和 UC 发病机制的理解，并可用于开发诊断或指导治疗。