Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.
Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.
复制标题
DOI：
10.3389/fimmu.2020.578505
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Steen H
中科院分区：
文献类型：
--
作者：
Bennike TB;Fatou B;Angelidou A;Diray-Arce J;Falsafi R;Ford R;Gill EE;van Haren SD;Idoko OT;Lee AH;Ben-Othman R;Pomat WS;Shannon CP;Smolen KK;Tebbutt SJ;Ozonoff A;Richmond PC;van den Biggelaar AHJ;Hancock REW;Kampmann B;Kollmann TR;Levy O;Steen H
新生儿对感染的易感性更高。其生物学机制尚未完全了解，但认为与免疫系统发育和生长期间的资源限制导致的免疫力年龄特异性适应有关。我们在这里提出了一个扩展的分析，我们的外周血血浆的蛋白质组学研究，从阴道分娩的健康足月新生儿的研究，收集在出生当天和生命的第一天（DOL）1，3，或7，以覆盖生命的第一周。使用我们建立的96孔板格式血浆蛋白质组学平台通过LC-MS表征血浆蛋白质组。我们发现增加急性期蛋白和DOL 1的相应抑制剂的减少。关注补体系统，我们发现从出生开始，经典补体途径和膜攻击复合物（MAC）的所有主要组分的血浆浓度增加，但C7除外，其似乎在出生时接近成人水平。相反，凝集素和补体旁路途径的成分主要减少。与全血信使RNA（mRNA）水平的比较能够平行表征mRNA和蛋白质水平，对于30种监测的补体蛋白中的23种，全血转录本信息本身并不能反映生命第一周期间的血浆蛋白水平或动力学。免疫球蛋白（IG）mRNA和蛋白水平的分析表明，IgM水平和合成增加，而母体转移的IgG 1 -4的血浆浓度根据其体内半衰期降低。与成人值相比，新生儿血浆中IgG 1与IgG 2 -4的比值增加，表明IgG 1经胎盘转移过程非常有效。母体IgG降解的部分补偿是通过IgG 1亚型的内源性合成实现的，IgG 1亚型随DOL的增加而增加。这些发现在一个地理上不同的队列中得到了验证，证明了新生儿免疫系统在人类生命的第一周内在各大洲的发展轨迹一致。我们的研究结果表明，经典的补体途径是新生儿免疫的核心，我们的方法来表征血浆蛋白质组与转录组平行将提供免疫个体发生的重要见解，并为预防和治疗疾病提供新的方法。
Neonates have heightened susceptibility to infections. The biological mechanisms are incompletely understood but thought to be related to age-specific adaptations in immunity due to resource constraints during immune system development and growth. We present here an extended analysis of our proteomics study of peripheral blood-plasma from a study of healthy full-term newborns delivered vaginally, collected at the day of birth and on day of life (DOL) 1, 3, or 7, to cover the first week of life. The plasma proteome was characterized by LC-MS using our established 96-well plate format plasma proteomics platform. We found increasing acute phase proteins and a reduction of respective inhibitors on DOL1. Focusing on the complement system, we found increased plasma concentrations of all major components of the classical complement pathway and the membrane attack complex (MAC) from birth onward, except C7 which seems to have near adult levels at birth. In contrast, components of the lectin and alternative complement pathways mainly decreased. A comparison to whole blood messenger RNA (mRNA) levels enabled characterization of mRNA and protein levels in parallel, and for 23 of the 30 monitored complement proteins, the whole blood transcript information by itself was not reflective of the plasma protein levels or dynamics during the first week of life. Analysis of immunoglobulin (Ig) mRNA and protein levels revealed that IgM levels and synthesis increased, while the plasma concentrations of maternally transferred IgG1-4 decreased in accordance with their in vivo half-lives. The neonatal plasma ratio of IgG1 to IgG2-4 was increased compared to adult values, demonstrating a highly efficient IgG1 transplacental transfer process. Partial compensation for maternal IgG degradation was achieved by endogenous synthesis of the IgG1 subtype which increased with DOL. The findings were validated in a geographically distinct cohort, demonstrating a consistent developmental trajectory of the newborn’s immune system over the first week of human life across continents. Our findings indicate that the classical complement pathway is central for newborn immunity and our approach to characterize the plasma proteome in parallel with the transcriptome will provide crucial insight in immune ontogeny and inform new approaches to prevent and treat diseases.