Cytokine and growth factor correlation networks associated with morbidities in extremely preterm infants
Veronika Golubinskaya1, Holger Nilsson2, Halfdan Rydbeck2,3
1Department of Physiology, Institute of Neuroscience and Physiology, University of Gothenburg, Sahlgrenska Academy, 432 40530, Gothenburg, Sweden. veronika.golubinskaya@gu.se.
Insights
Correlation network analysis reveals distinct protein signatures for retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) in preterm infants, identifying early disease characteristics not apparent from individual protein levels.
Area of Science:
- Neonatal Medicine
- Biochemistry
- Systems Biology
Background:
- Cytokines and growth factors (GF) are implicated in retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD).
- Subtle, coordinated changes in inflammatory proteins or GFs may indicate altered regulatory mechanisms.
- Correlation network analysis was employed to detect early disease characteristics.
Purpose of the Study:
- To determine early characteristics of ROP and BPD using correlation network analysis of serum factors.
- To identify protein signatures indicative of ROP and BPD development in extremely preterm infants.
- To uncover underlying pathophysiological mechanisms through protein interactions.
Main Methods:
- Measured concentrations of 17 cytokines and five GFs in blood samples from 72 extremely preterm infants.
- Collected samples at cord blood, day one, and during the first month of life.
- Constructed Spearman's correlation networks to differentiate between BPD/ROP patients and controls.
Main Results:
- Few individual cytokine levels differed significantly between ROP/BPD patients and controls.
- Distinct correlation networks of serum factors were characteristic of ROP and BPD and evolved over time.
- Specific proteins like EPO, G-CSF, IL-8, BDNF, VEGF-A (for ROP) and IL-1β, IGF-1, IL-17 (for BPD) were prominent in disease-specific networks.
Conclusions:
- Network analysis effectively identifies protein signatures associated with ROP and BPD in preterm infants.
- Interactions between serum factors, not individual levels, reveal crucial pathophysiological insights.
- This approach offers a novel method for understanding the early development of ROP and BPD.
Background:
Cytokines and growth factors (GF) have been implicated in the development of retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD). We hypothesize that even small coordinated changes in inflammatory proteins or GFs may reveal changes in underlying regulating mechanisms that do not induce obvious changes in concentration of individual proteins. We therefore applied correlation network analysis of serum factors to determine early characteristics of these conditions.
Methods:
Concentrations of 17 cytokines and five GFs were measured and analysed in blood samples from cord blood, on day one and during the following month in 72 extremely preterm infants. Spearman's correlation networks distinguishing BPD and severe ROP patients from non-affected were created.
Results:
Most cytokine concentrations correlated positively with each other and negatively with GFs. Very few individual cytokines differed between patients with and without ROP or BPD. However, networks of differently correlated serum factors were characteristic of the diseases and changed with time. In ROP networks, EPO, G-CSF and IL-8 (cord blood), BDNF and VEGF-A (first month) were prominent. In BPD networks, IL-1β, IGF-1 and IL-17 (day one) were noted.
Conclusions:
Network analysis identifies protein signatures related to ROP or BPD in extremely preterm infants. The identified interactions between serum factors are not evident from the analysis of their individual levels, but may reveal underlying pathophysiological mechanisms in the development of these diseases.
More Related Videos
07:36Modeling Encephalopathy of Prematurity Using Prenatal Hypoxia-ischemia with Intra-amniotic Lipopolysaccharide in Rats
Published on: November 20, 2015
11:00Multiplex Cytokine Profiling of Stimulated Mouse Splenocytes Using a Cytometric Bead-based Immunoassay Platform
Published on: November 9, 2017
Related Concept Videos
01:28Role of Hematopoietic Growth Factors
Thrombopoietin (TPO), mainly released by the liver,...
01:16TGF - β Signaling Pathway
02:26Protein Networks
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
01:24Regulation of Angiogenesis and Blood Supply
02:36Cells Coordinate Growth and Proliferation
02:04Covalently Linked Protein Regulators