Ma Li, Zhang Wei, Hou Mingxia, Li Dong, Liu Fengjuan, Du Xi, Jiang Peng, Wang Zongkui, Zhang Rong, Cao Haijun, Ye Shengliang, Li Changqing
Institute of Blood Transfusion, Chinese Academy of Medical Sciences, Chengdu, China.
Biomed Chromatogr. 2019 Apr;33(4):e4452. doi: 10.1002/bmc.4452. Epub 2018 Dec 21.
Intravenous immunoglobulin (IVIg) is increasingly used for the treatment of autoimmune and systemic inflammatory diseases with both licensed and off-label indications. Recent studies indicated that IVIg-mediated immunomodulation and anti-inflammation are closely associated with the IgG sialylation, especially with IgG crystallizable fragment (Fc) sialylation. The sialic acid levels of the IgG molecules and Fc fragments in 12 IVIg preparations from six Chinese manufacturers were evaluated. The Fc fragments were derived from the papain digestion of IVIg, followed by affinity and size exclusion chromatography. The sialic acid levels in Fc fragments and IVIg preparations were determined by high-performance liquid chromatography with fluorescence detection, after the sialic acid residues were released from the proteins. The results showed that the sialic acid levels in Chinese IVIg preparations ranged from 0.875 (mol/mol IgG) to 1.085 (mol/mol IgG), and the sialic acid levels in Fc fragments were from 0.321 (mol/mol Fc) to 0.361 (mol/mol Fc). Furthermore, the sialic acid levels of IVIg preparations and Fc fragments from different Chinese manufactures were significantly different. These findings will contribute to an increased understanding of Chinese IVIg preparations and the relationship between the sialic acid levels in IVIg preparations and their clinical efficacy in future clinical studies.
静脉注射免疫球蛋白（IVIg）越来越多地用于治疗具有许可和未标记适应症的自身免疫性疾病和全身性炎症性疾病。最近的研究表明，IVIg介导的免疫调节和抗炎作用与IgG糖基化密切相关，尤其是与IgG可结晶片段（Fc）糖基化相关。评估了来自六家中国制造商的12种IVIg制剂中IgG分子和Fc片段的唾液酸水平。Fc片段来自IVIg的木瓜蛋白酶消化，然后进行亲和色谱和尺寸排阻色谱。在唾液酸残基从蛋白质中释放后，通过荧光检测高效液相色谱法测定Fc片段和IVIg制剂中的唾液酸水平。结果表明，中国IVIg制剂中的唾液酸水平范围为0.875（mol/mol IgG）至1.085（mol/mol IgG），Fc片段中的唾液酸水平为0.321（mol/mol Fc）至0.361（mol/mol Fc）。此外，来自不同中国制造商的IVIg制剂和Fc片段的唾液酸水平存在显著差异。这些发现将有助于在未来的临床研究中加深对中国IVIg制剂的了解以及IVIg制剂中唾液酸水平与其临床疗效之间的关系。
