Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia.
Enrichment of sialylated IgG by lectin fractionation does not enhance the efficacy of immunoglobulin G in a murine model of immune thrombocytopenia.
复制标题
DOI：
10.1371/journal.pone.0021246
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Rispens T
中科院分区：
文献类型：
--
作者：
Guhr T;Bloem J;Derksen NI;Wuhrer M;Koenderman AH;Aalberse RC;Rispens T
静脉注射免疫球蛋白 G (IVIg) 广泛用于治疗一系列临床症状。为了将其用于免疫调节疗法，例如治疗免疫性血小板减少性紫癜，需要高剂量的 IVIg。有人认为，只有一小部分 IVIg 会产生这种抗免疫调节作用。最近的研究表明，该部分是 Fc-唾液酸化 IgG 部分。我们研究的目的是确定富含唾液酸化 IgG (IVIg-SA (+)) 的 IVIg 在被动免疫血小板减少症 (PIT) 小鼠模型中的功效。我们通过黑接骨木凝集素 (SNA) 凝集素分级富集 IVIg 的唾液酸化 IgG，并测定唾液酸化程度。使用基于凝集素的 ELISA 对 IVIg-SA (+) 进行分析表明，我们主要富集了 Fab 唾液酸化 IgG，而我们没有发现 Fc 唾液酸化 IgG 增加。质谱分析证实 SNA 凝集素分级后 Fc 唾液酸化没有改变。通过在注射大鼠抗小鼠血小板单克隆抗体前24小时施用IVIg或IVIg-SA (+)来测量唾液酸化IgG的功效。我们发现注射抗血小板单克隆抗体后血小板计数减少了 85%，注射 IVIg 后血小板计数减少了 70%（p<0.01）。相反，IVIg-SA (+)对血小板计数没有影响。 IVIg 和 IVIg-SA (+) 的血清水平相似，排除了 IgG 清除率增强这一可能的解释。我们的结果表明，SNA 凝集素分级分离不是富集 IVIg 中 Fc-唾液酸化 IgG 的合适方法。使用富含 Fab 唾液酸化 IgG 的 IVIg 消除了 IVIg 在小鼠 PIT 模型中的功效。
Intravenous immunoglobulin G (IVIg) is widely used against a range of clinical symptoms. For its use in immune modulating therapies such as treatment of immune thrombocytopenic purpura high doses of IVIg are required. It has been suggested that only a fraction of IVIg causes this anti immune modulating effect. Recent studies indicated that this fraction is the Fc-sialylated IgG fraction. The aim of our study was to determine the efficacy of IVIg enriched for sialylated IgG (IVIg-SA (+)) in a murine model of passive immune thrombocytopenia (PIT). We enriched IVIg for sialylated IgG by Sambucus nigra agglutinin (SNA) lectin fractionation and determined the degree of sialylation. Analysis of IVIg-SA (+) using a lectin-based ELISA revealed that we enriched predominantly for Fab-sialylated IgG, whereas we did not find an increase in Fc-sialylated IgG. Mass spectrometric analysis confirmed that Fc sialylation did not change after SNA lectin fractionation. The efficacy of sialylated IgG was measured by administering IVIg or IVIg-SA (+) 24 hours prior to an injection of a rat anti-mouse platelet mAb. We found an 85% decrease in platelet count after injection of an anti-platelet mAb, which was reduced to a 70% decrease by injecting IVIg (p<0.01). In contrast, IVIg-SA (+) had no effect on the platelet count. Serum levels of IVIg and IVIg-SA (+) were similar, ruling out enhanced IgG clearance as a possible explanation. Our results indicate that SNA lectin fractionation is not a suitable method to enrich IVIg for Fc-sialylated IgG. The use of IVIg enriched for Fab-sialylated IgG abolishes the efficacy of IVIg in the murine PIT model.
登录
查看更多内容
影响因子：
9.1
作者：
Negi, Vir-Singh;Elluru, Sriramulu;Kaveri, Srini V.
通讯作者：
Kaveri, Srini V.
影响因子：
20.3
作者：
Seite, Jean-Francois;Cornec, Divi;Hillion, Sophie
通讯作者：
Hillion, Sophie
影响因子：
3
作者：
Dalziel, M;McFarlane, I;Axford, JS
通讯作者：
Axford, JS
DOI：
10.1073/pnas.0810163105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Anthony, Robert M.;Wermeling, Fredrik;Ravetch, Jeffrey V.
通讯作者：
Ravetch, Jeffrey V.
影响因子：
6.2
作者：
SODERSTROM, T;SODERSTROM, R;ENSKOG, A
通讯作者：
ENSKOG, A