On the perplexingly low rate of transport of IgG2 across the human placenta.
On the perplexingly low rate of transport of IgG2 across the human placenta.
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DOI：
10.1371/journal.pone.0108319
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Vidarsson G
中科院分区：
文献类型：
--
作者：
Einarsdottir HK;Stapleton NM;Scherjon S;Andersen JT;Rispens T;van der Schoot CE;Vidarsson G
新生儿受体FcRn介导血清半衰期延长以及妊娠期间母体IgG向胎儿的主动转运。因此，运输效率和半衰期是密切相关的。然而，虽然人IgG 2亚类的半衰期与IgG 1相当，但IgG 2的胎盘转运却不相当，新生儿IgG 1水平通常超过出生时的母体水平，但IgG 2则不然。我们假设IgG 2独特的短铰链结构，使其κ-而不是λ-同种型形成至少三种不同的结构同种型，可能是这些差异的一个促成因素。为了研究是否存在对任一轻链的偏好，我们测量了27对匹配的母子对中IgG亚类以及IgG 1和IgG 2的κ/λ-轻链同种型的胎盘转运。我们还研究了小鼠中IgG 1和IgG 2轻链同种型以及合成的IgG 2结构同种型κA和κB的半衰期。为了研究IgG 1和IgG 2轻链同种型在人体中的血清清除率，我们在IVIg输注后4周定量了低丙种球蛋白血症患者中IgG 1和IgG 2轻链的相对比例，并与原始IVIg同种型组成进行了比较。我们的研究结果均未表明FcRn介导的机制（半衰期延长或母体转运）中存在任何轻链偏好。
The neonatal receptor, FcRn, mediates both serum half–life extension as well as active transport of maternal IgG to the fetus during pregnancy. Therefore, transport efficiency and half-life go hand-in-hand. However, while the half-life of the human IgG2 subclass is comparable to IgG1, the placental transport of IgG2 is not, with the neonatal IgG1 levels generally exceeding maternal levels at birth, but not for IgG2. We hypothesized that the unique short-hinged structure of IgG2, which enables its κ-, but not λ-isotype to form at least three different structural isoforms, might be a contributing factor to these differences. To investigate whether there was any preference for either light chain, we measured placental transport of IgG subclasses as well as κ/λ-light chain isotypes of IgG1 and IgG2 in 27 matched mother-child pairs. We also studied the half-life of IgG1 and IgG2 light chain isotypes in mice, as well as that of synthesized IgG2 structural isotypes κA and κB. In order to investigate serum clearance of IgG1 and IgG2 light-chain isotypes in humans, we quantified the relative proportions of IgG1 and IgG2 light chains in hypogammaglobulinemia patients four weeks after IVIg infusion and compared to the original IVIg isotype composition. None of our results indicate any light chain preference in either of the FcRn mediated mechanisms; half-life extension or maternal transport.
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