目的：与自身抗体阴性的类风湿关节炎(RA)患者相比，自身抗体阳性的RA患者不易出现妊娠期RA疾病活动性改善(DAS28(CRP))。抗瓜氨酸蛋白抗体(ACPAs)是RA最特异的自身抗体。我们先前已证明疾病的改善与总IgG糖基化的改变有关，IgG糖基化可调节抗体效应器功能。因此，我们试图分析妊娠期间ACPA IgG糖基化谱，以了解自身抗体阳性RA患者妊娠诱导改善较低的原因。

        方法：这是一项旨在研究RA妊娠相关改善的前瞻性队列研究，从ACPA阳性RA患者血清(n=112)中纯化ACPA-IgG。应用质谱法对ACPA IgG的片段(Fc)糖基化谱进行分析，并与来自同一患者或ACPA阴性患者的总IgG进行比较。

        结果：所有ACPA-IgG亚类在妊娠期间显示半乳糖基化和唾液酸化水平的显著变化，虽然不如总IgG的变化显著。妊娠诱导的ACPA-IgG半乳糖基化增加，而非唾液酸化，与低DAS28(CRP)相关。在ACPA阳性RA患者中，没有发现与总IgG半乳糖基化的改变相关，而在ACPA阴性患者中，疾病活动性的变化与总IgG半乳糖基化的改变相关。

        结论：在ACPA阳性RA患者中，妊娠诱导的ACPA-IgG半乳糖基化改变，而不是总的IgG，与疾病活动性的改变相关。这些数据提示在ACPA阳性患者中，ACPA-IgG的半乳糖基化比总IgG更具致病相关性。

        附原文：AbstractOBJECTIVES:Patients with autoantibody-positiverheumatoid arthritis(RA) are less likely to experiencepregnancy-induced improvement of RA disease activity (DAS28-C reactive protein (CRP)) compared with patients with autoantibody-negative RA. Anti-citrullinated protein antibodies (ACPAs) are the most specific autoantibodies for RA. We previously demonstrated that disease improvement is associated with changes in total IgG glycosylation, which regulate antibody effector function. Therefore, we sought to analyse the ACPA-IgG glycosylation profile duringpregnancywith the aim to understand the lower change ofpregnancy-induced improvement of the disease in patients with autoantibody-positive RA.METHODS:ACPA-IgGs were purified from ACPA-positive patient sera (n=112) of thePregnancy-induced Amelioration ofRheumatoid Arthritiscohort, a prospective study designed to investigatepregnancy-associated improvement of RA. The fragment crystallisable (Fc)glycosylation profile of ACPA-IgGs was characterised by mass spectrometry and compared with that of total IgG derived from the same patients or from ACPA-negative patients.RESULTS:All ACPA-IgG subclasses display significant changes in the level of galactosylation and sialylation duringpregnancy, although less pronounced than in total IgG. Thepregnancy-induced increase in ACPA-IgG galactosylation, but not sialylation, associates with lower DAS28-CRP. In ACPA-positive patients, no such association was found with changes in the galactosylation of total IgG, whereas in ACPA-negative patients changes in disease activity correlated well with changes in the galactosylation of total IgG.CONCLUSIONS:In ACPA-positive RA, thepregnancy-induced change in galactosylation of ACPA-IgG, and not that of total IgG, associates with changes in disease activity. These data may indicate that in ACPA-positive patients the galactosylation of ACPA-IgG is of more pathogenic relevance than that of total IgG.

        引自Bondt A,Hafkenscheid L,Falck D,etal.ACPA IgG galactosylation associates with disease activity in pregnant patients withrheumatoid arthritis.Ann Rheum Dis.2018 Apr 3. pii: annrheumdis-2018-212946. doi: 10.1136/annrheumdis-2018-212946. [Epub ahead of print]