Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis
Anti-citrullinated protein antibodies acquire a pro-inflammatory Fc glycosylation phenotype prior to the onset of rheumatoid arthritis
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DOI：
10.1136/annrheumdis-2013-203565
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发表时间：
2015-01-01
影响因子：
27.4
通讯作者：
Scherer, Hans U.
中科院分区：
文献类型：
--
作者：
Rombouts, Yoann;Ewing, Ewoud;Scherer, Hans U.
目的探讨抗核蛋白抗体(ACPA)在关节炎发病前Fc糖基化的特异性变化。方法收集183例ACPA阳性关节痛患者在发病前及随访不同时间点的血清标本。105例患者在中位12个月后(IQR6-24)发展为关节炎，并根据1987年美国风湿病学会(ACR)标准将其分为类风湿性关节炎(RA，n=48)和未分化关节炎(UA，n=57)。用亲和纯化的方法分离ACPA和血清总免疫球蛋白，并用胰酶进行酶切。用纳米液相色谱质谱对ACPA-IgG1Fc-糖肽进行分析，并与总Ig G1进行比较。结果在基线水平，关节痛患者ACPA-IgG1和总Ig G1Fc糖基化模式相似。相比之下，在关节炎发作时，ACPA在RA患者中显示出半乳糖残留量的减少，但在UA患者中则没有。这一下降发生在确诊前3个月左右，与全身炎症(血沉速率)的增加平行。类风湿性关节炎患者总IgG1的半乳糖基化水平也降低，但这并不是关节炎发生的先兆。有趣的是，我们还注意到在基线时ACPA-IgG1 Fc核心岩藻糖化程度高于总IgG1，在诊断前进一步增加。这些向更倾向于炎症表型的变化可能参与了推动疾病进程。
Objective To determine whether anticitrullinated protein antibodies (ACPA) exhibit specific changes in Fc glycosylation prior to the onset of arthritis.Methods Serum samples of patients with ACPA-positive arthralgia (n=183) were collected at baseline and at various time points of follow-up. 105 patients developed arthritis after a median of 12 months (IQR 6-24) and were classified as having either rheumatoid arthritis (RA, n=48) or undifferentiated arthritis (UA, n=57) based on the 1987 American College of Rheumatology (ACR) criteria. ACPA and total serum IgG were isolated by affinity purification and cleaved by trypsin. ACPA-IgG1 Fc-glycopeptides were subsequently analysed by nano-liquid chromatography mass spectrometry and compared to those of total IgG1.Results At baseline, ACPA-IgG1 and total IgG1 from arthralgia patients displayed similar Fc glycosylation patterns. By contrast, at the onset of arthritis, ACPA exhibited a decrease in galactose residues in RA patients, but not in UA patients. This decrease occurred around 3 months prior to diagnosis and was paralleled by an increase in systemic inflammation (erythrocyte sedimentation rate). Galactosylation of total IgG1 was also decreased in RA, but this did not precede the onset of arthritis. Interestingly, we additionally noted a higher degree of ACPA-IgG1 Fc core fucosylation at baseline as compared with total IgG1, which further increased prior to diagnosis.Conclusions ACPA display significant changes in Fc galactosylation and fucosylation prior to the onset of RA. These changes towards a more pro-inflammatory phenotype could be involved in driving the disease process.