Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases.
Glycosylation of Immunoglobulin G Associates With Clinical Features of Inflammatory Bowel Diseases.
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DOI：
10.1053/j.gastro.2018.01.002
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发表时间：
2018-04
期刊：
影响因子：
29.4
通讯作者：
Lauc G
中科院分区：
文献类型：
--
作者：
Šimurina M;de Haan N;Vučković F;Kennedy NA;Štambuk J;Falck D;Trbojević-Akmačić I;Clerc F;Razdorov G;Khon A;Latiano A;D'Incà R;Danese S;Targan S;Landers C;Dubinsky M;Inflammatory Bowel Disease Biomarkers Consortium;McGovern DPB;Annese V;Wuhrer M;Lauc G
炎症性肠病的原因尚不清楚，最突出的形式克罗恩病（CD）和溃疡性结肠炎（UC）有时很难区分。免疫球蛋白G（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-糖基化的变化，以及不同患者组的疾病特征。我们分析了从CD患者（意大利874例患者和美国[US] 391例患者）或UC患者（意大利1056例患者和美国253例患者）和健康个体（对照）（意大利427例患者和美国440例患者）的2个独立队列中获得的3441份血浆样本。通过液相色谱-质谱联用分析IgG Fc-糖基化（胰蛋白酶糖肽）。我们分析了疾病状态（UC与对照，CD与对照，UC与CD）和糖肽性状之间的关联，以及临床特征和糖肽性状之间的关联，使用logistic回归模型，年龄和性别作为协变量。CD或UC患者的IgG半乳糖基化水平低于对照组。例如，CD患者中IgG 1半乳糖基化的比值比（OR）为0. 59（95% CI，0. 51 - 0. 69），UC患者为0. 81（95% CI，0. 71 - 0. 92）。CD患者与对照组相比IgG岩藻糖基化增加（IgG 1：OR，1.27; 95% CI，1.12-1.44），但UC患者与对照组相比IgG岩藻糖基化降低（IgG 23：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患者与对照组（IgG 1：OR，0.69; 95% CI，0.54-0.89）和CD患者与对照组（IgG 23：OR，0.78; 95% CI，0.66-0.91）的手术需求。在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（与对照组相比）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，并用于开发诊断或指导治疗。
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 immunoglobulin G (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. We analyzed 3441 plasma samples, obtained from 2 independent cohorts of patients with CD (874 patients in Italy and 391 in the United States [US]) or UC (1056 in Italy and 253 in the US and healthy individuals (controls) (427 in Italy and 440 in the US). 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. 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% 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). 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.
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克罗恩病和溃疡性结肠炎表型的遗传决定因素：遗传关联研究。
DOI：
10.1016/s0140-6736(15)00465-1
发表时间：
2016-01-09
期刊：
Lancet (London, England)
影响因子：
--
作者：
Cleynen I;Boucher G;Jostins L;Schumm LP;Zeissig S;Ahmad T;Andersen V;Andrews JM;Annese V;Brand S;Brant SR;Cho JH;Daly MJ;Dubinsky M;Duerr RH;Ferguson LR;Franke A;Gearry RB;Goyette P;Hakonarson H;Halfvarson J;Hov JR;Huang H;Kennedy NA;Kupcinskas L;Lawrance IC;Lee JC;Satsangi J;Schreiber S;Théâtre E;van der Meulen-de Jong AE;Weersma RK;Wilson DC;International Inflammatory Bowel Disease Genetics Consortium;Parkes M;Vermeire S;Rioux JD;Mansfield J;Silverberg MS;Radford-Smith G;McGovern DP;Barrett JC;Lees CW
通讯作者：
Lees CW
影响因子：
3.8
作者：
Ferrara, C;Brünker, P;Umaña, P
通讯作者：
Umaña, P
影响因子：
4.3
作者：
Bennike, Tue;Birkelund, Svend;Andersen, Vibeke
通讯作者：
Andersen, Vibeke
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
4.9
作者：
Dubinsky MC;Kugathasan S;Kwon S;Haritunians T;Wrobel I;Wahbeh G;Quiros A;Bahar R;Silber G;Farrior S;Stephens M;Teleten N;Panikkath D;Ippoliti A;Vasiliauskas E;Fleshner P;Williams C;Landers C;Rotter JI;Targan SR;Taylor KD;McGovern DP
通讯作者：
McGovern DP