The vulnerable foetus Genes and the environment present two distinct pathways towards immune tolerance or an 'early warning' reaction. In very early life scientists report that both genes and the environment can impact simultaneously, thus setting patterns for future life. Following birth, the immune testing of the environment continues and accelerates.
House dust mites Over 12 years ago doctors, investigating pregnant women who were continually exposed to dust mite allergens during pregnancy, reported the presence of the major mite allergen (Der p1) in foetal fluid at 16 to 17 weeks of gestation. The women had all undergone amniocentesis at that time and chose to continue their pregnancy to full term. At 22 weeks foetal immune response to Der p1 was detected. Continuing the study to full term, the doctors noted that, in some cases, Der p1 was found to be at higher levels in blood and urine of the newborn than in that of the mother. They were surprised to note in one case Der p1 was significantly (110%) higher in the newborn than in the mother's blood, whereas, in the amniotic fluid at 16 weeks gestation Der p1 can be barely detectable. This finding led the research team to speculate that foetal exposure to Der p1 can be accumulative. It is of interest to note that at full term the baby is swallowing 700 mL of amniotic fluid per day and is able to absorb 10% of the macromolecules within the fluid.
Der p1 is an active digestive enzyme considered small enough to cross the placenta into the amniotic fluid. The enzyme is known to 'cleave' important elements that bind cells together causing cell death and a breach in lung defences. What influence Der p1 has on a developing (genetically vulnerable) foetus has yet to be fully described, however performance of the gene ADAM33, so called 'asthma gene', can present a clue.
ADAM33 ??? the asthma gene Clusters of genes are associated with allergy and lung disease, but one of the most well studied and interesting is ADAM33. This gene (discovered in 2002) normally sits quietly as a connective tissue component tethered to cells such as in the smooth muscle located just underneath lung cells. However, if damaged by 'cleaving' it can turn into an active enzyme creating a tunnelling system of micro-blood vessels and thickening of the smooth muscle. The reason for the increase in blood vessels is to help deliver powerful immune defences that will swing into action upon invasion of pathogens, be they viral, bacterial or recognised allergens. Der p1 from dust mites can be considered in this grouping. Scientists suspect ADAM33 may be 'cleaved' before or shortly following birth thus creating a protective immune system primed to react to environmental insults later in life. In this scenario ADAM33 is not alone. There are other candidate genes such as Matrix metalloproteinase 12, but that's another story.
ADAM33 is a life long resident in lung tissue. Repeated morphing of the 'asthma gene' in its microenvironment may result in altered barrier function and disordered lung tissue, (known as remodelling) a syndrome of many respiratory diseases, in young and old alike.
Research findings Doctors report that a loss of lung-power can be detected as early as 4 weeks of age. However, recently a clinical study demonstrated that children, at high-risk from asthma, can be protected from the disease through environmental and dietary manipulation. The children were followed from infancy through to eighteen years of age. The report on the study states, 'early intervention within the first few months of life is likely to be crucial in preventing the remodelling of airways which is the hallmark of asthma'.
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