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

2020 ◽  
Vol 11 ◽  
Author(s):  
Tue Bjerg Bennike ◽  
Benoit Fatou ◽  
Asimenia Angelidou ◽  
Joann Diray-Arce ◽  
Reza Falsafi ◽  
...  
Keyword(s):  
Immune System ◽  
System Development ◽  
Human Life ◽  
Plasma Concentrations ◽  
Plasma Proteome ◽  
Complement Pathway ◽  
Classical Complement Pathway ◽  
Protein Levels ◽  
Immune System Development ◽  
Classical Complement

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.

scholarly journals Carbamylation of immunoglobulin abrogates activation of the classical complement pathway

2014 ◽  
Vol 44 (11) ◽  
pp. 3403-3412 ◽  
Author(s):  
Catalin Koro ◽  
Ewa Bielecka ◽  
Anders Dahl‐Knudsen ◽  
Jan J. Enghild ◽  
Carsten Scavenius ◽  
...  
Keyword(s):  
Complement Pathway ◽  
Classical Complement Pathway ◽  
Classical Complement

scholarly journals Osteopontin Levels in Human Milk Are Related to Maternal Nutrition and Infant Health and Growth

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2670
Author(s):  
Aysegül Aksan ◽  
Izzet Erdal ◽  
Siddika Songül Yalcin ◽  
Jürgen Stein ◽  
Gülhan Samur
Keyword(s):  
Immune System ◽  
Breast Milk ◽  
Infant Health ◽  
Maternal Nutrition ◽  
System Development ◽  
Maternal Factors ◽  
Immune System Development ◽  
The Mean ◽  
Pregnancy Weight

Background: Osteopontin (OPN) is a glycosylated phosphoprotein found in human tissues and body fluids. OPN in breast milk is thought to play a major role in growth and immune system development in early infancy. Here, we investigated maternal factors that may affect concentrations of OPN in breast milk, and the possible associated consequences for the health of neonates. Methods: General characteristics, health status, dietary patterns, and anthropometric measurements of 85 mothers and their babies were recorded antenatally and during postnatal follow-up. Results: The mean concentration of OPN in breast milk was 137.1 ± 56.8 mg/L. Maternal factors including smoking, BMI, birth route, pregnancy weight gain, and energy intake during lactation were associated with OPN levels (p < 0.05). Significant correlations were determined between body weight, length, and head circumference, respectively, and OPN levels after one (r = 0.442, p = < 0.001; r = −0.284, p = < 0.001; r = −0.392, p = < 0.001) and three months (r = 0.501, p = < 0.001; r = −0.450, p = < 0.001; r = −0.498, p = < 0.001) of lactation. A negative relation between fever-related infant hospitalizations from 0–3 months and breast milk OPN levels (r = −0.599, p < 0.001) was identified. Conclusions: OPN concentrations in breast milk differ depending on maternal factors, and these differences can affect the growth and immune system functions of infants. OPN supplementation in infant formula feed may have benefits and should be further investigated.

scholarly journals Herpes Simplex Virus Type 1 and 2 Glycoprotein C Prevents Complement-Mediated Neutralization Induced by Natural Immunoglobulin M Antibody

2006 ◽  
Vol 80 (8) ◽  
pp. 4038-4046 ◽  
Author(s):  
Lauren M. Hook ◽  
John M. Lubinski ◽  
Ming Jiang ◽  
Michael K. Pangburn ◽  
Harvey M. Friedman
Keyword(s):  
Herpes Simplex ◽  
Human Serum ◽  
Immunoglobulin M ◽  
Complement Pathway ◽  
Glycoprotein C ◽  
Classical Complement Pathway ◽  
Simplex Virus ◽  
Classical Complement ◽  
Hsv 1

ABSTRACT Glycoprotein C (gC) of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) binds complement component C3b and protects virus from complement-mediated neutralization. Differences in complement interacting domains exist between gC of HSV-1 (gC1) and HSV-2 (gC2), since the amino terminus of gC1 blocks complement C5 from binding to C3b, while gC2 fails to interfere with this activity. We previously reported that neutralization of HSV-1 gC-null virus by HSV antibody-negative human serum requires activation of C5 but not of downstream components of the classical complement pathway. In this report, we evaluated whether activation of C5 is sufficient to neutralize HSV-2 gC-null virus, or whether formation of the membrane attack complex by C6 to C9 is required for neutralization. We found that activation of the classical complement pathway up to C5 was sufficient to neutralize HSV-2 gC-null virus by HSV antibody-negative human serum. We evaluated the mechanisms by which complement activation occurred in seronegative human serum. Interestingly, natural immunoglobulin M antibodies bound to virus, which triggered activation of C1q and the classical complement pathway. HSV antibody-negative sera obtained from four individuals differed over an approximately 10-fold range in their potency for complement-mediated virus neutralization. These findings indicate that humans differ in the ability of their innate immune systems to neutralize HSV-1 or HSV-2 gC-null virus and that a critical function of gC1 and gC2 is to prevent C5 activation.

I11 Pharmacologic inhibition of the classical complement pathway enhances neuronal function and HD R6/2 mouse survival

2021 ◽  
Author(s):  
Alessia Tassoni ◽  
Vidhu Mathur ◽  
Joseph Vereen ◽  
Ellen Cahir-McFarland ◽  
Sethu Sankaranarayanan ◽  
...  
Keyword(s):  
Complement Pathway ◽  
Neuronal Function ◽  
Classical Complement Pathway ◽  
Pharmacologic Inhibition ◽  
Classical Complement
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