目的：與自身抗體陰性的類風濕關節炎(RA)患者相比，自身抗體陽性的RA患者不易出現妊娠期RA疾病活動性改善(DAS28(CRP))。抗瓜氨酸蛋白抗體(ACPAs)是RA最特異的自身抗體。我們先前已證明疾病的改善與總IgG糖基化的改變有關，IgG糖基化可調節抗體效應器功能。因此，我們試圖分析妊娠期間ACPA IgG糖基化譜，以了解自身抗體陽性RA患者妊娠誘導改善較低的原因。

方法：這是一項旨在研究RA妊娠相關改善的前瞻性隊列研究，從ACPA陽性RA患者血清(n=112)中純化ACPA-IgG。應用質譜法對ACPA IgG的片段(Fc)糖基化譜進行分析，並與來自同一患者或ACPA陰性患者的總IgG進行比較。

結果：所有ACPA-IgG亞類在妊娠期間顯示半乳糖基化和唾液酸化水平的顯著變化，雖然不如總IgG的變化顯著。妊娠誘導的ACPA-IgG半乳糖基化增加，而非唾液酸化，與低DAS28(CRP)相關。在ACPA陽性RA患者中，沒有發現與總IgG半乳糖基化的改變相關，而在ACPA陰性患者中，疾病活動性的變化與總IgG半乳糖基化的改變相關。

結論：在ACPA陽性RA患者中，妊娠誘導的ACPA-IgG半乳糖基化改變，而不是總的IgG，與疾病活動性的改變相關。這些數據提示在ACPA陽性患者中，ACPA-IgG的半乳糖基化比總IgG更具致病相關性。

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]