Papers of the Month
By Sara Amolegbe
PFAS exposure in infancy linked to reduced vaccine response
A new NIEHS-funded study linked perfluorinated alkylate substance (PFAS) exposure during infancy to decreased immune response to vaccinations at age 5 years. This study extended previous findings that PFAS exposure may interfere with the effectiveness of some childhood vaccinations and provided new evidence that children may be the most vulnerable during their first 6 months.
The research team studied children in the Faroe Islands, which lie halfway between Scotland and Iceland. The Faroese have PFAS levels similar to those of U.S. residents. PFAS concentrations were measured in the children’s blood at birth, at 18 months, and at 5 years. Because PFASs can be transferred to babies through breast milk, PFAS exposure in infancy was estimated from the PFAS exposure level at birth and the duration of exclusive breastfeeding.
In this study, the antibody response to tetanus and diphtheria vaccines was weaker in 5 year olds who had the highest PFAS exposure levels between ages 3 and 6 months. The researchers found that tetanus antibody concentrations at age 5 years were decreased by 19 to 29 percent with each doubling of PFAS exposure in early infancy.
The researchers observed associations between reduced immune response to the two vaccinations and increased PFAS concentrations at age 18 months and 5 years, but the associations were stronger between ages 3 and 6 months. According to the authors, these findings supported the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy, and PFAS exposure might prevent children from developing the normal immune response to some vaccinations.
Grandjean P, Heilmann C, Weihe P, Nielsen F, Mogensen UB, Timmermann A, Budtz-Joergensen E. 2017. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years. J Immunotoxicol 14(1):188–195.
Motor and cognitive impairment from poorly processed cassava
NIEHS-funded researchers and colleagues showed that exposure to poorly processed cassava was linked to impaired motor and cognitive performance in children, especially boys, over time. By measuring a marker in urine, the researchers were able to identify children at risk for neurological impairment before they exhibited clear clinical symptoms.
Cassava, which is a subsistence crop for more than 600 million people around the world, can contain cyanide if not properly detoxified by methods such as soaking with water and then drying in the sun. Consumption of improperly prepared cassava is associated with neurological conditions, including konzo, a disorder that can lead to irreversible paralysis of the legs.
The researchers assessed cognitive and motor performance in children with and without konzo in the town of Kahemba, Congo. They also measured levels of thiocyanate, a marker of recent cyanide exposure, in the children’s urine.
They showed that children with konzo had impaired motor skills at least 4 years after konzo diagnosis, and that boys without konzo performed better on cognitive tests than boys with konzo. They also found an association between reduced motor proficiency and increased levels of urinary thiocyanate in boys with and without konzo, but not in girls. By measuring this specific marker in urine, the researchers documented that boys not diagnosed with konzo may be on the threshold of neuropsychological impairment, possibly because of ongoing exposure to poorly processed cassava.
According to the authors, the urinary thiocyanate indicator could be used with community-wide, household-based health education to identify children at risk for neurodevelopmental disabilities and to reduce their exposure.
Boivin MJ, Okitundu D, Makila-Mabe B, Sombo MT, Mumba D, Sikorskii A, Mayambu B, Tshala-Katumbay D. 2017. Cognitive and motor performance in Congolese children with konzo during 4 years of follow-up: a longitudinal analysis. Lancet Glob Health 5(9):e936–e947.
New model simulates lung function in mice
A new computer-based mouse lung model, developed by NIEHS-funded researchers, simulates how changes in lung structure affect respiratory function. The model is intended to provide a simpler way to measure the relative importance of lung structure changes resulting from different factors, including exposure to potentially harmful chemicals.
Chronic inflammation, which is often found in people with chronic obstructive pulmonary disease (COPD), can alter lung structure and impact breathing. The researchers examined lung tissue and function in healthy mice and in mice that mimicked conditions seen in people with emphysema, a type of COPD. They developed the new model of lung function that analyzes air flow and throat pressure data, as well as the relationship between these data and other lung changes.
Using this model, the researchers compared how lung function was affected by factors associated with chronic inflammation. These factors included lung tissue destruction, changes in the density of elastic fiber structures that help the lung walls stretch and contract during breathing, and changes in lung recruitment, which refers to increased pressure to keep lung regions open that might otherwise collapse.
Modeling results suggested that changes in lung recruitment and elastic fiber density were primarily responsible for observed decreases in lung function associated with chronic inflammatory disease in the mice.
Massa CB, Groves AM, Jaggernauth SU, Laskin DL, Gow AJ. 2017. Histologic and biochemical alterations predict pulmonary mechanical dysfunction in aging mice with chronic lung inflammation. PloS Comput Biol 13(8):e1005570.
Differences in AS3MT enzyme may increase risk of arsenic-related diseases
People with certain forms of the enzyme arsenic-3-methyltranferase (AS3MT) may retain arsenic longer in their bodies and may have an increased risk for arsenic-related diseases according to an NIEHS-funded study. The AS3MT enzyme metabolizes arsenic into a form that can be removed from the body. The structure of the enzyme can vary in humans.
The researchers identified eight variants of the human AS3MT enzyme, each of which contained single substitutions in amino acids, the building blocks of proteins. They characterized the properties of the variant enzymes and found that compared with AS3MT with no amino acid substitutions, the variants exhibited lower stability and decreased binding activity, which led to less efficient arsenic metabolism. The researchers predicted that individuals with these variants would have a higher proportion of monomethyl-arsenic, a more toxic arsenic metabolite linked to arsenic-related diseases. They also predicted that individuals with these variants would retain arsenic in their body for more time.
By determining the consequences of the single amino acid substitutions, the authors provided information about how the structure of the enzyme might be used to predict differences in arsenic metabolism. Understanding the variations in AS3MT might help explain why exposure to arsenic may lead to adverse health effects in some people and not in others.
Li J, Packianathan C, Rossman TG, Rosen BP. . 2017. Nonsynonymous polymorphisms in the human AS3MT arsenic methylation gene: implications for arsenic toxicity. Chem Res Toxicol 30(7):1481–1491.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)