IgG Fc N-Glycosylation in Guillain-Barre Syndrome Treated with Immunoglobulins
IgG Fc N-Glycosylation in Guillain-Barre Syndrome Treated with Immunoglobulins
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DOI：
10.1021/pr401213z
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发表时间：
2014-03-01
影响因子：
4.4
通讯作者：
Jacobs, Bart C.
中科院分区：
文献类型：
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作者：
Fokkink, Willem-Jan R.;Selman, Maurice H. J.;Jacobs, Bart C.
静脉注射免疫球蛋白（IVIg）是格林-巴利综合征（GBS）的首选治疗方法。格林-巴利综合征是一种免疫介导的周围神经病变，可导致快速进行性肢体无力和呼吸衰竭。IVIg在自身免疫性疾病中的作用机制尚未阐明，但以往的研究表明，IgG fc部分的n -糖基化可能介导了一些抗炎作用。GBS是研究这些影响的模型疾病，因为GBS是一种通常影响健康人的急性单相疾病，可以用IVIg的标准疗程治疗，尽管临床反应变化很大。在本研究中，研究了GBS患者在IVIg治疗前后血清IgG的n -糖基化与临床病程和转归的关系。采用液相色谱-质谱法分别测定血清IgG1和IgG2的糖型。这些IgG亚类分别从174例CBS患者在标准IVIg治疗方案前和150例患者治疗2周后的血清中纯化。与年龄和性别匹配的对照组相比，未接受治疗的CBS患者IgG1和IgG2的半乳糖化水平较低。与患者血清IgG相比，IVIg制剂中含有较高水平的半乳糖化和唾液化IgG Fc糖型。IVIg治疗导致血清中IgG1和IgG2的fc -半乳糖基化和-唾液酰化水平升高。血清IgG Fc糖基化的正常化程度因患者而异。多元logistic回归分析显示，尽管接受Mg治疗，但IgG半乳糖基化和唾液酰化水平持续较低的患者，其CBS形式最为严重，需要呼吸机支持的频率更高。Kaplan Meier分析显示，与IgG Fc糖基化正常的患者相比，这些患者需要更多的时间才能再次行走。总之，我们的研究结果表明，CBS患者血清IgG Fc糖基化与Mg治疗后疾病严重程度和临床恢复有关，可能有助于制定新的措施来监测治疗效果。
Intravenous immunoglobulin (IVIg) is the treatment of choice for Guillain-Barre syndrome (GBS), an immune-mediated peripheral neuropathy causing rapidly progressive limb weakness and respiratory failure. The working mechanism of IVIg in autoimmune diseases has not been elucidated, but previous studies indicate that some anti-inflammatory effects may be mediated by the N-glycosylation of the Fc-portion of IgG. GBS is a model disease to investigate these effects because GBS is an acute and monophasic disorder usually affecting healthy persons, which is treated with a standard course of IVIg, although the clinical response is highly variable. In the current study, the N-glycosylation of the Fc-portion of serum IgG was investigated in patients with GBS before and after treatment with IVIg in relation to clinical course and outcome. Glycoforrns of serum IgG1 and IgG2 were determined separately by liquid chromatography mass spectrometry. These IgG subclasses were purified from the serum of 174 CBS patients before and in 150 patients 2 weeks after standard IVIg treatment regimen. Treatment-naive CBS patients compared with age-and sex-matched controls had lower levels of galactosylation of IgG1 and IgG2. IVIg preparations contained relatively high levels of galactosylated and sialylated IgG Fc glycoforms compared with serum IgG in patients. Treatment with IVIg resulted in an increase in serum of the Fc-galactosylation and -sialylation of both IgG1 and IgG2. The extent of normalization in serum IgG Fc glycosylation varied between patients. Multiple logistic regression analysis showed that patients with persistent low IgG galactosylation and sialylation despite Mg treatment had the most severe forms of CBS and needed ventilator support more often. Kaplan Meier analysis showed that these patients also needed more time to be able to walk again compared with patients with a normalized IgG Fc glycosylation profile. In conclusion, our results suggest that serum IgG Fc glycosylation in CBS is related to disease severity and clinical recovery after Mg and may help to develop new measures to monitor the efficacy of treatment.