Changes in anti-thyroglobulin IgG glycosylation patterns in Hashimoto's thyroiditis patients.

Changes in anti-thyroglobulin IgG glycosylation patterns in Hashimoto's thyroiditis patients.
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桥本甲状腺炎患者抗甲状腺球蛋白 IgG 糖基化模式的变化

DOI:
10.1210/jc.2014-2921
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发表时间:
2015-02
期刊:
The Journal of clinical endocrinology and metabolism
影响因子:
--
通讯作者:
Guo X
Guo X
中科院分区:
其他
文献类型:
--
作者:
Yuan S;Li Q;Zhang Y;Huang C;Wu H;Li Y;Liu Y;Yu N;Zhang H;Lu G;Gao Y;Gao Y;Guo X

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已知桥本甲状腺炎(HT)患者的血清表现出升高的抗甲状腺球蛋白IgG(TgAb IgG)水平。因此,TgAb IgG代表这种使人衰弱的自身免疫性疾病的标志。本研究的目的是探讨HT患者和健康献血员TgAb IgG特异性糖基化模式的差异表达。根据电化学发光免疫法检测血清TgAb水平,将32例HT患者分为中度组(mHT,n = 15)和高度组(hHT,n = 17)。用亲和层析法从HT组和对照组(n = 15)的血清中纯化TgAb IgG。进行MALDI-QIT-TOF-MS/MS光谱法以鉴定纯化的TgAb IgG的糖基化谱。使用凝集素微阵列技术比较HT患者和对照之间以及mHT和hHT组之间TgAb IgG上发现的不同聚糖的丰度。MALDI-QIT-TOF-MS/MS的结果显示,mHT、hHT和对照组之间TgAb IgG的糖基化谱相似。此外,凝集素微阵列显示,与对照组相比,(所有P < .001),存在较高水平的(1)甘露糖(检测为凝集素LCA、VFA和MNA-M);(2)末端唾液酸(检测为SNA-I和PSA);(3)核心岩藻糖(检测为LcH);和(4)Gal(β1-4)GlcNAc(β1-2)Man聚糖(检测为PHA-L)。在hHT和mHT组之间观察到类似的趋势,与mHT组相比,在hHT组中发现TgAb IgG上的甘露糖、末端唾液酸、核心岩藻糖和Gal(β1-4)GlcNAc(β1-2)Man聚糖水平升高(均P <0.05)。HT患者的TgAb IgG表现出比健康对照的TgAb IgG所观察到的更高的糖基化水平。本研究结果为探讨TgAb在HT发病机制中的作用提供了新的线索。
Sera of Hashimoto's thyroiditis (HT) patients are known to exhibit elevated levels of anti-thyroglobulin IgG (TgAb IgG). Therefore, TgAb IgG represents a hallmark of this debilitating autoimmune disease. The aim of our study was to investigate the differential expression of specific glycosylation patterns of TgAb IgG from HT patients and healthy blood donors. HT patients (n = 32) were divided into two subgroups, medium level group (mHT, n = 15) and high level group (hHT, n = 17), according to the serum levels of TgAb detected by electrochemiluminescence immunoassay. TgAb IgG was purified by affinity chromatography from the sera of the HT group and control group (n = 15). MALDI-QIT-TOF-MS/MS spectrometry was performed to identify the glycosylation profiles of purified TgAb IgG. Lectin microarray technology was used to compare the abundance of different glycans found on TgAb IgG between HT patients and controls, and between the mHT and hHT groups. The results by MALDI-QIT-TOF-MS/MS showed that the glycosylation profiles of TgAb IgG were similar between the mHT, hHT, and control groups. Furthermore, the lectin microarray showed that compared to the control group (all P < .001), there were higher levels present of (1) mannose (detected as lectin LCA, VFA, and MNA-M); (2) terminal sialic acid (detected as SNA-I and PSA); (3) core fucose (detected as LcH); and (4) Gal(β1–4)GlcNAc(β1–2)Man glycans (detected as PHA-L) on TgAb IgG from the HT group. A similar trend was observed between the hHT and mHT group, with elevated levels of mannose, terminal sialic acid, core fucose, and Gal(β1–4)GlcNAc(β1–2)Man glycans on TgAb IgG found in the hHT group compared with the mHT group (all P < .05). TgAb IgG of HT patients exhibits higher glycosylation levels than those observed for TgAb IgG of healthy controls. Our results provide new clues for exploring the role of TgAb in the pathogenesis of HT.
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