Dataset Information

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

ABSTRACT: 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.

SUBMITTER: Bennike TB

PROVIDER: S-EPMC7732455 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

Bennike Tue Bjerg TB Fatou Benoit B Angelidou Asimenia A Diray-Arce Joann J Falsafi Reza R Ford Rebecca R Gill Erin E EE van Haren Simon D SD Idoko Olubukola T OT Lee Amy H AH Ben-Othman Rym R Pomat William S WS Shannon Casey P CP Smolen Kinga K KK Tebbutt Scott J SJ Ozonoff Al A Richmond Peter C PC van den Biggelaar Anita H J AHJ Hancock Robert E W REW Kampmann Beate B Kollmann Tobias R TR Levy Ofer O Steen Hanno H

Frontiers in immunology 20201020

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. ...[more]

PMID: 33329546

Similar Datasets

Project description:Introduction: Early life is characterized by heightened susceptibility to infections and is recognized as a major determinant of the immune system development and the overall health for the entire human lifespan. However, our knowledge of the development of the neonatal immune system is incomplete, limiting the development of novel preventative and therapeutic strategies, especially in newborns. To gain insight into the early immune system development and plasma proteome ontogeny, the Expanded Program on Immunization Consortium (EPIC) led by Professor Ofer Levy MD at Boston Children’s Hospital, Harvard Medical School and Tobias R. Kollmann Telethon Kids Institute, Australia as part of the Human Immunological Project Consortium (HIPC), established two independent cohorts of plasma from healthy newborns born by vaginal delivery during the first week of life. Methods: Blood samples were collected from 30 newborns in The Gambia (Medical Research Council Unit, The Gambia) at the day of birth (day of life, DOL 0) and at one of the follow-up visits on DOL1, DOL3, or DOL7. A similar validation cohort was collected in Papua New Guinea (PNG) (Institute for Medical Research, Papua New Guinea, Australasian) from 19 newborns. The plasma proteome was characterized by LC-MS on a Q Exactive using the proven and published plasma proteomics platform developed in the Steen Laboratory, led by Dr Hanno Steen, Director of Proteomics at Boston Children’s Hospital, Harvard Medical School, employing only microliter of plasma prepared in a 96-well plate format. The data was analyzed with MaxQuant. Results: We characterized 385 blood-plasma proteins. Utilizing the paired study design, we identified consistent changes related to ontogeny and cellular growth pathways in the blood-plasma proteome. Conclusion: This dataset allows for studying the early ontogeny of the plasma proteome, and in extension the early immune system development, in two independent healthy cohorts. Characterization of the plasma proteome may provide novel insight into new approaches to prevent, detect, and treat infectious diseases. Acknowledgements: We would like to thank all the participating families and all past and current members of the EPIC-HIPC, and the Steen Laboratory, without whom this study would not be possible. A special recognition goes to the teams who established the unique cohorts in The Gambia, by Professor Beate Kampmann and Dr Olubukola T. Idoko at The Gambia at the London School of Hygiene and Tropical Medicine, The Gambia, and in PNG, by Anita H.J. van der Biggelaar and William S. Pomat at Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, University of Western Australia Perth, Australia.

Project description:Introduction/background & aimsEarly life is marked by distinct and rapidly evolving immunity and increased susceptibility to infection. The vulnerability of the newborn reflects development of a complex immune system in the face of rapidly changing demands during the transition to extra-uterine life. Cytokines and chemokines contribute to this dynamic immune signaling network and can be altered by many factors, such as infection. Newborns undergo dynamic changes important to health and disease, yet there is limited information regarding human neonatal plasma cytokine and chemokine concentrations over the first week of life. The few available studies are limited by small sample size, cross-sectional study design, or focus on perturbed host states like severe infection or prematurity. To characterize immune ontogeny among healthy full-term newborns, we assessed plasma cytokine and chemokine concentrations across the first week of life in a robust longitudinal cohort of healthy, full-term African newborns.MethodsWe analyzed a subgroup of a cohort of healthy newborns at the Medical Research Council Unit in The Gambia (West Africa; N = 608). Peripheral blood plasma was collected from all study participants at birth (day of life (DOL) 0) and at one follow-up time point at DOL 1, 3, or 7. Plasma cytokine and chemokine concentrations were measured by bead-based cytokine multiplex assay. Unsupervised clustering was used to identify patterns in plasma cytokine and chemokine ontogeny during early life.ResultsWe observed an increase across the first week of life in plasma Th1 cytokines such as IFNγ and CXCL10 and a decrease in Th2 and anti-inflammatory cytokines such as IL-6 and IL-10, and chemokines such as CXCL8. In contrast, other cytokines and chemokines (e.g. IL-4 and CCL5, respectively) remained unchanged during the first week of life. This robust ontogenetic pattern did not appear to be affected by gestational age or sex.ConclusionsOntogeny is a strong driver of newborn plasma-based levels of cytokines and chemokines throughout the first week of life with a rising IFNγ axis suggesting post-natal upregulation of host defense pathways. Our study will prove useful to the design and interpretation of future studies aimed at understanding the neonatal immune system during health and disease.

Project description:Central nervous system and visual dysfunction is an unfortunate consequence of systemic hypoxia in the setting of cardiopulmonary disease, including infection with SARS-CoV-2, high-altitude cerebral edema and retinopathy and other conditions. Hypoxia-induced inflammatory signaling may lead to retinal inflammation, gliosis and visual disturbances. We investigated the consequences of systemic hypoxia using serial retinal optical coherence tomography and by assessing the earliest changes within 24h after hypoxia by measuring a proteomics panel of 39 cytokines, chemokines and growth factors in the plasma and retina, as well as using retinal histology. We induced severe systemic hypoxia in adult C57BL/6 mice using a hypoxia chamber (10% O2) for 1 week and rapidly assessed measurements within 1h compared with 18h after hypoxia. Optical coherence tomography revealed retinal tissue edema at 18h after hypoxia. Hierarchical clustering of plasma and retinal immune molecules revealed obvious segregation of the 1h posthypoxia group away from that of controls. One hour after hypoxia, there were 10 significantly increased molecules in plasma and 4 in retina. Interleukin-1β and vascular endothelial growth factor were increased in both tissues. Concomitantly, there was significantly increased aquaporin-4, decreased Kir4.1, and increased gliosis in retinal histology. In summary, the immediate posthypoxic period is characterized by molecular changes consistent with systemic and retinal inflammation and retinal glial changes important in water transport, leading to tissue edema. This posthypoxic inflammation rapidly improves within 24h, consistent with the typically mild and transient visual disturbance in hypoxia, such as in high-altitude retinopathy. Given hypoxia increases risk of vision loss, more studies in at-risk patients, such as plasma immune profiling and in vivo retinal imaging, are needed in order to identify novel diagnostic or prognostic biomarkers of visual impairment in systemic hypoxia.

Dataset Information

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

Publications

Preparing for Life: Plasma Proteome Changes and Immune System Development During the First Week of Human Life.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets