IgG4 glycosylation contributes to the pathogenesis of IgG4 Hashimoto's thyroiditis via the complement pathway.

IF 3.5 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM
European Thyroid Journal Pub Date : 2024-10-24 Print Date: 2024-10-01 DOI:10.1530/ETJ-24-0156
Chenxu Zhao, Zhiming Sun, Shuaihang Wang, Jixin Zhang, Jumei Liu, Lei Chen, Guizhi Lu, Yang Yu, Ying Gao
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引用次数: 0

Abstract

Background: To explore whether IgG4 is involved in the pathogenesis of IgG4 HT.

Methods: Serum TgAb IgG4 and TPOAb IgG4 were measured in IgG4 HT and non-IgG4 HT. C1q, mannose-binding lectin (MBL), Bb, C3d, C4d, and membrane attack complex (MAC) in thyroid tissues from IgG4 HT, non-IgG4 HT, and controls were examined by immunohistochemistry. We assessed IgG4 and MAC deposition in mouse thyroid by immunohistochemistry after injecting purified IgG4 into mice. The glycosylation patterns of TgAb IgG4 from IgG4 HT were identified by MALDI-TOF-MS. The ability of IgG4 to bind to MBL before and after deglycosylation was assessed by ELISA. MBL and MAC fluorescence were detected in thyrocytes after the addition of IgG4 or deglycosylated IgG4.

Results: Serum TgAb IgG4 and TPOAb IgG4 levels were significantly higher in the IgG4 HT group. MBL, Bb, C3d, C4d, and MAC levels were significantly higher in the thyroid tissues of IgG4 HT than in non-IgG4 HT (all P < 0.001). IgG4 colocalized with MBL by immunofluorescence. In mice, follicular cell structure disruption was observed after the injection of IgG4 from IgG4 HT, as well as the colocalization of IgG4 with MAC. High levels of TgAb IgG4 glycosylation patterns, including monogalactose glycan (G1F), galactose-deficient glycan (G0F), and high-mannose glycan (M5), were detected in IgG4 HT. After deglycosylation, IgG4 reduced its ability to bind to MBL, and there was low MBL and MAC activation in thyrocytes.

Conclusion: High levels of IgG4 glycosylation patterns, including G1F, G0F, and M5, may activate the complement lectin pathway, thereby participating in the pathogenesis of IgG4 HT.

IgG4 糖基化通过补体途径促进了 IgG4 桥本氏甲状腺炎的发病机制。
背景:探讨 IgG4 是否参与 IgG4 HT 的发病机制:探讨IgG4是否参与IgG4 HT的发病机制:方法:测定 IgG4 HT 和非 IgG4 HT 患者的血清 TgAb IgG4 和 TPOAb IgG4。免疫组化法检测了 IgG4 HT、非 IgG4 HT 和对照组甲状腺组织中的 C1q、甘露糖结合凝集素(MBL)、Bb、C3d、C4d 和膜攻击复合物(MAC)。给小鼠注射纯化的IgG4后,我们用免疫组化方法评估了IgG4和MAC在小鼠甲状腺中的沉积情况。通过 MALDI-TOF-MS 鉴定了来自 IgG4 HT 的 TgAb IgG4 的糖基化模式。通过 ELISA 评估了脱糖前后 IgG4 与 MBL 结合的能力。加入 IgG4 或脱糖 IgG4 后,在甲状腺细胞中检测 MBL 和 MAC 荧光:结果:血清 TgAb IgG4 和 TPOAb IgG4 水平在 IgG4 HT 中较高。与非 IgG4 HT 相比,IgG4 HT 甲状腺组织中的 MBL、Bb、C3d、C4d 和 MAC 水平更高(均 P <0.001)。通过免疫荧光,IgG4 与 MBL 共同定位。在小鼠体内注射来自 IgG4 HT 的 IgG4 后,可观察到滤泡细胞结构的破坏以及 IgG4 与 MAC 的共聚焦。在 IgG4 HT 中检测到了高水平的 TgAb IgG4 糖基化模式,包括单半乳糖聚糖(G1F)、半乳糖缺陷聚糖(G0F)和高甘露糖聚糖(M5)。脱糖后,IgG4与MBL的结合能力降低,甲状腺细胞中的MBL和MAC活化程度低:结论:包括G1F、G0F和M5在内的高水平IgG4糖基化模式可能会激活补体凝集素通路,从而参与IgG4 HT的发病机制。
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来源期刊
European Thyroid Journal
European Thyroid Journal Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
6.70
自引率
2.10%
发文量
156
期刊介绍: The ''European Thyroid Journal'' publishes papers reporting original research in basic, translational and clinical thyroidology. Original contributions cover all aspects of the field, from molecular and cellular biology to immunology and biochemistry, from physiology to pathology, and from pediatric to adult thyroid diseases with a special focus on thyroid cancer. Readers also benefit from reviews by noted experts, which highlight especially active areas of current research. The journal will further publish formal guidelines in the field, produced and endorsed by the European Thyroid Association.
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