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      The maternal plasma proteome changes as a function of gestational age in normal pregnancy: a longitudinal study

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          Abstract

          <div class="section"> <a class="named-anchor" id="S1"> <!-- named anchor --> </a> <h5 class="section-title" id="d10187536e239">Objective</h5> <p id="P1">Pregnancy is accompanied by dramatic physiologic changes in maternal plasma proteins. Characterization of the maternal plasma proteome in normal pregnancy is an essential step for understanding changes to predict pregnancy outcome. The objective of this study was to describe maternal plasma proteins that change in abundance with advancing gestational age, and determine biological processes that are perturbed in normal pregnancy. </p> </div><div class="section"> <a class="named-anchor" id="S2"> <!-- named anchor --> </a> <h5 class="section-title" id="d10187536e244">Materials and methods</h5> <p id="P2">A longitudinal study included 43 normal pregnancies that had a term delivery of an infant who was appropriate for gestational age (AGA) without maternal or neonatal complications. For each pregnancy, 3 to 6 maternal plasma samples (median=5,) were profiled to measure the abundance of 1,125 proteins using multiplex assays. Linear mixed effects models with polynomial splines were used to model protein abundance as a function of gestational age, and significance of the association was inferred via likelihood ratio tests. Proteins considered to be significantly changed were defined as having: 1) more than 1.5 fold change between 8 and 40 weeks of gestation; and 2) a false discovery rate (FDR) adjusted p-value &lt;0.1. Gene ontology enrichment analysis was employed to identify biological processes over-represented among the proteins that changed with advancing gestation. </p> </div><div class="section"> <a class="named-anchor" id="S3"> <!-- named anchor --> </a> <h5 class="section-title" id="d10187536e249">Results</h5> <p id="P3">1) Ten percent (112/1,125) of the profiled proteins changed in abundance as a function of gestational age; 2) of the 1,125 proteins analyzed Glypican-3, sialic acid-binding immunoglobulin-type lectins (Siglec)-6, placental growth factor (PlGF), C-C motif (CCL)-28, carbonic anhydrase 6, Prolactin (PRL), interleukin-1 receptor 4 (IL-1 R4), dual specificity mitogen-activated protein kinase 4 (MP2K4) and pregnancy-associated plasma protein-A (PAPP-A) had more than 5 fold change in abundance across gestation. These 9 proteins are known to be involved in a wide range of both physiologic and pathologic processes, such as growth regulation, embryogenesis, angiogenesis immunoregulation, inflammation etc.; and 3) biological processes associated with protein changes in normal pregnancy included defense response, defense response to bacteria, proteolysis and leukocyte migration (FDR=10%). </p> </div><div class="section"> <a class="named-anchor" id="S4"> <!-- named anchor --> </a> <h5 class="section-title" id="d10187536e254">Conclusions</h5> <p id="P4">The plasma proteome of normal pregnancy demonstrates dramatic changes in both magnitude of changes and the fraction of the proteins involved. Such information is important to understand the physiology of pregnancy, development of biomarkers to differentiate normal vs. abnormal pregnancy, and determine the response to interventions. </p> </div>

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          Most cited references 260

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            For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign.
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               Tomas Ganz (2003)
              The production of natural antibiotic peptides has emerged as an important mechanism of innate immunity in plants and animals. Defensins are diverse members of a large family of antimicrobial peptides, contributing to the antimicrobial action of granulocytes, mucosal host defence in the small intestine and epithelial host defence in the skin and elsewhere. This review, inspired by a spate of recent studies of defensins in human diseases and animal models, focuses on the biological function of defensins.
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                Author and article information

                Journal
                American Journal of Obstetrics and Gynecology
                American Journal of Obstetrics and Gynecology
                Elsevier BV
                00029378
                July 2017
                July 2017
                : 217
                : 1
                : 67.e1-67.e21
                Article
                10.1016/j.ajog.2017.02.037
                5813489
                28263753
                © 2017

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