Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up
Low galactosylation of IgG associates with higher risk for future diagnosis of rheumatoid arthritis during 10 years of follow-up
复制标题
DOI：
10.1016/j.bbadis.2018.03.018
复制
发表时间：
2018-06-01
影响因子：
6.2
通讯作者：
Lauc, Gordan
中科院分区：
文献类型：
--
作者：
Gudelj, Ivan;Salo, Perttu P.;Lauc, Gordan
已知抗体在类风湿性关节炎(RA)的发展中起着重要作用，RA是最常见的慢性炎症性疾病之一，主要累及关节。大多数RA患者产生了抗免疫球蛋白G(Ig G)的自身抗体，且Ig G糖基化的改变与RA有关。我们进行了这项研究，以确定改变的免疫球蛋白糖基化是否在疾病诊断之前。我们在两个前瞻性队列(N=14,749)中通过测量179名在10年内发展为类风湿关节炎的受试者和358名匹配对照的28项免疫球蛋白糖链特征来研究类风湿关节炎中的免疫球蛋白糖基化。采用基于亲水相互作用的超高效液相色谱(HILIC-UPLC)方法对免疫球蛋白多糖进行分析。未来的类风湿关节炎诊断与与低半乳糖化和唾液酸化的免疫球蛋白相关的特征有关，当病例与匹配的对照组比较时。在类风湿性关节炎病例中，这些特征与从被招募到研究到被诊断为类风湿性关节炎之间的时间(中位数时间4.31年)无关。免疫球蛋白糖基化的差异是相对稳定的，并存在于诊断前的几年。这表明影响免疫球蛋白糖基组成的长效因素是类风湿性关节炎的潜在机制之一，而半乳糖化水平降低是参与疾病发展的一个预先存在的危险因素。
Antibodies are known to have an important role in the development of rheumatoid arthritis (RA), one of the most prevalent chronic inflammatory diseases which primarily involves the joints. Most RA patients develop auto antibodies against immunoglobulin G (IgG) and changes in IgG glycosylation have been associated with RA. We undertook this study to determine whether altered IgG glycosylation precedes the disease diagnosis. We studied IgG glycosylation in RA in two prospective cohorts (N = 14,749) by measuring 28 IgG glycan traits in 179 subjects who developed RA within 10-years follow-up and 358 matched controls. Ultra-performance liquid chromatography method based on hydrophilic interactions (HILIC-UPLC) was used to analyse IgG glycans. Future RA diagnosis associated with traits related to lower galactosylation and sialylation of IgG when comparing the cases to the matched controls. In RA cases, these traits did not correlate with the time between being recruited to the study and being diagnosed with RA (median time 4.31 years). The difference in IgG glycosylation was relatively stable and present years before diagnosis. This indicates that long-acting factors affecting IgG glycome composition are among the underlying mechanisms of RA and that decreased galactosylation is a preexisting risk factor involved in the disease development.