Multiple Juvenile Idiopathic Arthritis Subtypes Demonstrate Proinflammatory IgG Glycosylation
Multiple Juvenile Idiopathic Arthritis Subtypes Demonstrate Proinflammatory IgG Glycosylation
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DOI：
10.1002/art.34507
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发表时间：
2012-09-01
影响因子：
--
通讯作者：
Nigrovic, Peter A.
中科院分区：
文献类型：
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作者：
Ercan, Altan;Barnes, Michael G.;Nigrovic, Peter A.
客观的。类风湿性关节炎与过量的半乳糖化 (G0) IgG 相关，而半乳糖化 (G0) IgG 被认为是相对促炎的。幼年特发性关节炎 (JIA) 中这种关联的评估因年龄依赖性 IgG 聚糖变异而变得复杂。本研究的目的是对健康儿童和 JIA 患者的 IgG 聚糖进行首次大规模调查，重点关注儿童早期，即 JIA 发病高峰期。方法。使用高效液相色谱法对来自健康儿童和未接受过缓解疾病抗风湿药物的幼年特发性关节炎患者的 IgG 聚糖进行了表征。参照单半乳糖基化 (G1) 种类对半乳糖基化聚糖进行定量。寻找 G0:G1 比率与疾病特征之间的关联。结果。在 9 个月至 16 岁的健康儿童 (n = 165) 中，G0:G1 比率高度依赖于年龄，3 岁以下儿童的比率达到峰值 1.19，10 岁后降至最低点 0.83（Spearman's rho = 0.60，P < 0.0001）。 JIA 患者 (n = 141) 的 G0:G1 比率比对照受试者升高（1.32 对比 1.02；P < 0.0001）。在所有 JIA 亚型中，根据年龄校正的 G0:G1 比率异常高（未评估附着点炎相关关节炎），在系统性 JIA 中最为引人注目。糖基化异常在有抗核抗体的患者和无抗核抗体的患者中以及在早发型和晚发型疾病中具有可比性，并且最多表现出与炎症标记物的弱相关性。结论。在健康儿童中，尤其是在生命的最初几年，IgG 糖基化偏向于促炎性 G0 变异。这种偏差在幼年特发性关节炎患者中更为严重。 IgG 聚糖变异在儿童免疫功能中的作用，包括幼年特发性关节炎的好发性，仍有待确定。
Objective. Rheumatoid arthritis is associated with an excess of agalactosylated (G0) IgG that is considered relatively proinflammatory. Assessment of this association in juvenile idiopathic arthritis (JIA) is complicated by age-dependent IgG glycan variation. The aim of this study was to conduct the first large-scale survey of IgG glycans in healthy children and patients with JIA, with a focus on early childhood, the time of peak JIA incidence.Methods. IgG glycans from healthy children and disease-modifying antirheumatic drug-naive patients with JIA were characterized using high-performance liquid chromatography. Agalactosylated glycans were quantitated with reference to monogalactosylated (G1) species. Associations were sought between the G0:G1 ratio and disease characteristics.Results. Among healthy children ages 9 months to 16 years (n = 165), the G0:G1 ratio was highly age dependent, with the ratio peaking to 1.19 in children younger than age 3 years and declining to a nadir of 0.83 after age 10 years (Spearman's rho = 0.60, P < 0.0001). In patients with JIA (n = 141), the G0:G1 ratio was elevated compared with that in control subjects (1.32 versus 1.02; P < 0.0001). The G0:G1 ratio corrected for age was abnormally high in all JIA subtypes (enthesitis-related arthritis was not assessed), most strikingly in systemic JIA. Glycosylation aberrancy was comparable in patients with and those without antinuclear antibodies and in both early- and late-onset disease and exhibited at most a weak correlation with markers of inflammation.Conclusion. IgG glycosylation is skewed toward proinflammatory G0 variants in healthy children, in particular during the first few years of life. This deviation is exaggerated in patients with JIA. The role for IgG glycan variation in immune function in children, including the predilection of JIA for early childhood, remains to be defined.