Kwon Hyewon, Crisostomo Amanda C, Smalls Hayley Marie, Finke John M
Department of Medicinal Chemistry, University of Washington, Seattle, Washington, United States of America.
Division of Science and Mathematics, University of Washington, Tacoma, Washington, United States of America.
PLoS One. 2015 Mar 31;10(3):e0120420. doi: 10.1371/journal.pone.0120420. eCollection 2015.
The fraction of IgG antibodies with anti-oligomeric Aβ affinity and surface sialic acid was compared between Octagam and Gammagard intravenous immunoglobulin (IVIG) using two complementary surface plasmon resonance methods. These comparisons were performed to identify if an elevated fraction existed in Gammagard, which reported small putative benefits in a recent Phase III clinical trial for Alzheimer's Disease. The fraction of anti-oligomeric Aβ IgG was found to be higher in Octagam, for which no cognitive benefits were reported. The fraction and location of surface-accessible sialic acid in the Fab domain was found to be similar between Gammagard and Octagam. These findings indicate that anti-oligomeric Aβ IgG and total surface sialic acid alone cannot account for reported clinical differences in the two IVIG products. A combined analysis of sialic acid in anti-oligomeric Aβ IgG did reveal a notable finding that this subgroup exhibited a high degree of surface sialic acid lacking the conventional α2,6 linkage. These results demonstrate that the IVIG antibodies used to engage oligomeric Aβ in both Gammagard and Octagam clinical trials did not possess α2,6-linked surface sialic acid at the time of administration. Anti-oligomeric Aβ IgG with α2,6 linkages remains untested as an AD treatment.
使用两种互补的表面等离子体共振方法，比较了Octagam和Gammagard静脉注射免疫球蛋白（IVIG）中具有抗寡聚体Aβ亲和力和表面唾液酸的IgG抗体比例。进行这些比较是为了确定Gammagard中是否存在升高的比例，Gammagard在最近一项针对阿尔茨海默病的III期临床试验中报告了一些假定的小益处。结果发现，Octagam中抗寡聚体Aβ IgG的比例较高，而Octagam未报告有认知益处。Gammagard和Octagam之间Fab结构域中表面可及唾液酸的比例和位置相似。这些发现表明，仅抗寡聚体Aβ IgG和总表面唾液酸不能解释两种IVIG产品报告的临床差异。对抗寡聚体Aβ IgG中的唾液酸进行综合分析确实发现了一个显著结果，即该亚组表现出高度缺乏传统α2,6连接的表面唾液酸。这些结果表明，在Gammagard和Octagam临床试验中用于结合寡聚体Aβ的IVIG抗体在给药时不具有α2,6连接的表面唾液酸。具有α2,6连接的抗寡聚体Aβ IgG作为阿尔茨海默病治疗方法仍未经过测试。
