Bondt Albert, Wuhrer Manfred, Kuijper T Martijn, Hazes Johanna M W, Dolhain Radboud J E M
Department of Rheumatology, Erasmus University Medical Center, PO Box 2400, 3000, CA, Rotterdam, The Netherlands.
Center for Proteomics and Metabolomics, Leiden University Medical Center, 2300, RC, Leiden, The Netherlands.
Arthritis Res Ther. 2016 Nov 25;18(1):274. doi: 10.1186/s13075-016-1172-1.
Changes in immunoglobulin G (IgG) constant domain (Fc) glycosylation are associated with changes in rheumatoid arthritis (RA) disease activity in response to pregnancy. Here, we sought to determine whether the same holds true for variable domain (Fab) glycosylation.
IgGs were captured from RA and control sera obtained before (RA only), during and after pregnancy, followed by Fc and Fab separation, glycan release, and mass spectrometric detection. In parallel, glycans from intact IgG were analysed. The data was used to calculate glycosylation traits, and to estimate the level of Fab glycosylation.
The overall level of Fab glycosylation was increased in RA patients compared to controls, while no differences in Fab glycosylation patterns were found. For the Fc and intact IgG (Total) previously observed differences in galactosylation and bisection were confirmed. Furthermore, increased galactosylation of Fc and Total were associated with lower disease activity and autoantibody positivity. In addition, the change in Fc galactosylation associated with the change in disease activity during pregnancy and after delivery, while this was not the case for Fab.
In contrast to changes in Fc glycosylation, changes in Fab glycosylation are not associated with improvement of RA during pregnancy and arthritis flare after delivery.
免疫球蛋白G（IgG）恒定区（Fc）糖基化的变化与类风湿关节炎（RA）在孕期疾病活动度的变化相关。在此，我们试图确定可变区（Fab）糖基化是否也是如此。
从妊娠前（仅RA组）、妊娠期间及产后获取的RA患者和对照血清中捕获IgG，随后进行Fc和Fab分离、聚糖释放及质谱检测。同时，对完整IgG的聚糖进行分析。这些数据用于计算糖基化特征，并估计Fab糖基化水平。
与对照组相比，RA患者的Fab糖基化总体水平升高，但未发现Fab糖基化模式存在差异。先前观察到的Fc和完整IgG（总IgG）在半乳糖基化和分支方面的差异得到了证实。此外，Fc和总IgG半乳糖基化增加与较低的疾病活动度和自身抗体阳性相关。另外，Fc半乳糖基化的变化与孕期及产后疾病活动度的变化相关，而Fab则不然。
与Fc糖基化变化不同，Fab糖基化变化与孕期RA病情改善及产后关节炎发作无关。
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