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Umbilical Cord Blood Proteomics Could Offer Insights into Infant Development, Diagnostics

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By Adam Bonislawski

A team led by scientists at Arizona State's Biodesign Institute has performed one of the most comprehensive proteomic characterizations to date of blood from human umbilical cords.

Their study, which was published last month in the online edition of Environmental Health Perspectives, identified 1,210 proteins in human UCB, a more than six-fold increase over previous studies. Among these were proteins associated with 138 different metabolic and disease pathways as well as 38 proteins currently approved by the US Food and Drug Administration as biomarkers for adults.

Scientists have performed extensive proteomic characterizations of adult human blood over the past decade, but the infant blood proteome has received far less study. However, as research has emerged suggesting that long-term outcomes such as diabetes, obesity, and chronic heart and kidney diseases could have roots in fetal development and exposure, the need for early diagnostics and prognostics for infant and child health has grown.

While adult blood is typically easy to obtain for proteomic research, obtaining large quantities of newborn blood can be more difficult due to worries about adding to the health strains on the child and mother. The advantage of UCB "is that the blood can be acquired in relatively large quantities non-invasively from the child," said ASU researcher Nicole Hansmeier, the first author on the EHP study.

"The differences in the [proteome] composition between infant and adult are actually largely not known," Hansmeier told ProteoMonitor in an e-mail this week, noting that exploring these differences was one of the primary goals of the project.

Using MALDI-MS/MS on an Applied Biosystems 4800 MALDI-TOF/TOF instrument, the researchers analyzed 12 UCB samples acquired from the cord blood cohort collection of the Baltimore Tracking Health Related Environmental Exposures study and identified a total of 1,210 non-redundant human proteins. According to the authors, the most comprehensive characterization of the UCB proteome done previously identified 207 unique proteins.

Comparing these proteins to an adult human plasma proteome reference set published last year by researchers from the Institute for Systems Biology and the Swiss Federal Institute of Technology, they found 295 proteins that were present in both the UCB and adult proteomes.

The identified differences in the UCB and adult proteins were likely due to both "sampling depth and expression dynamics," Hansmeier said. She added that "due to the different demands during child development, it is very likely that the infant blood proteome differs in its dynamics somewhat from adult blood."

In addition, she noted that the differences were likely also due in part to the fact that "many blood proteomic studies [have been] taken from a relatively limited number of individuals."

Among the 295 proteins present in both the UCB and adult proteomes were 38 proteins currently approved by FDA as adult biomarkers, including markers for deficiency of thyroid binding, chronic kidney dysfunctions, hypercoagulation disorders, and cardiovascular disease. These proteins the authors identified as the "highest priority" for follow up, noting that while the markers have been approved for adults, "it is conceivable that [they] are also of diagnostic value in infants."

Hansmeier noted, however, that for regulatory reasons and due to the fact that many of the mechanisms underlying these markers are not truly understood, further clinical trials will be need to validate the use of adult biomarkers in infants.

The researchers also identified a number of proteins that are known to be diagnostic of exposure to toxic substances, including proteins linked to in utero exposure to tobacco products as well as exposure to dioxins, phenols, mold, methylmercury, organochlorines, and antenatal administration of the corticosteroid betamethasone, which is used as a topical cream for skin irritation as well as an agent to stimulate fetal lung maturation and has been linked to hypoglycemia and leukocytosis in newborns exposed in utero.

The study, Hansmeier said, aimed to expand the basic knowledge of infant biology as well as identify analytes with prognostic or diagnostic potential for diseases originating in infancy or affecting newborns.

"Diabetes is a very good example, but also other, possibly more subtle adverse reactions due to, [for example,] toxic exposures or infections, could be detected early on," she said.

Recently several researchers including Neil Dalton, professor of pediatric biochemistry at King's College London, and Denis Hochstrasser, chairman of Geneva University Hospital's Genetic & Laboratory Medicine Department, have begun using proteomics to perform infant screening for blood diseases like sickle cell anemia and thalassemia (PM 12/9/2011). This work has largely used dried blood spot samples, as opposed to UCB, however.

Moving forward, Hansmeier said, the ASU researchers plan to do a deeper analysis of the UCB proteome "to investigate whether and how organohalogen exposure may affect protein expression patterns and whether predictive markers for harmful exposure can be derived from them.

Such compounds are widely used in construction materials as well as consumer and medical goods. Prenatal exposure to some OHCs has been linked to motor, cognitive, and behavioral development in children.


Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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