Household size linked to allergic sensitization
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Researchers found an association between larger households and higher naive regulatory T-cell levels, which in turn were associated with less allergic sensitization and disease at age 12 months, according to a study.
There also were associations between multiple prenatal and postnatal microbial factors and the development of naive T regulatory (nTreg) and activated T regulatory (aTreg) cells, the researchers wrote in the study, published in Pediatric Allergy and Immunology.
Led by Anne-Louise Ponsonby, BMedSci, MBBS, PhD, FAFPHM, FRACP, professor with the Florey Institute of Neuroscience and Mental Health in Parkville, Australia, the researchers said that FoxP3-positive Treg cells help maintain immune tolerance to foods and other environmental allergens.
In response to antigenic immunostimulation, the researchers continued, nTreg cells in circulation can become aTreg cells. Previously, the researchers had reported that deficits of nTreg cells at birth predict food allergy at age 1 year.
The researchers examined data — including 19 prenatal environmental microbial factors — from the Barwon Infant Study of 1,074 infants born to women recruited between June 2010 and June 2013.
Among the 463 infants whose Treg levels were measured at birth via cord blood, those with larger family sizes of three or more residents and one or more siblings had higher proportions of nTreg in their cord blood (P < .0001).
The researchers also found associations between higher nTreg levels and a range of environmental microbial factors at age 6 and 12 months (n = 191). For example, exclusive or mixed breastfeeding vs. no breastfeeding had stronger associations with higher nTreg levels at age 6 months.
The researchers further found little association between environmental microbial factors and aTreg proportions at birth; however, they did find an association between larger household size and higher aTreg levels at age 6 months.
At age 12 months, there were associations between higher aTreg levels and dog ownership and higher maternal and paternal occupational social contact, the researchers found, including evidence of dose-response.
Across the first postnatal year, higher nTreg (P < .001) and aTreg (P = .007) proportions were found among infants from larger households, with higher nTreg proportions found among infants with a pet dog (P = .01).
Further, breastfed infants had higher longitudinal nTreg and aTreg proportions. Those who attended formal childcare had higher longitudinal nTreg (P = .02) but not aTreg proportions in the first postnatal year.
Based on a receiver operating characteristic analysis, the researchers found that infants with 3% or more nTreg at birth were markedly less likely to experience allergic outcomes including food allergy (adjusted OR = 0.21; 95% CI, 0.09-0.5) and atopic eczema (aOR = 0.26; 95% CI, 0.1-0.64).
Also, the researchers found a strong association between polysensitization at age 1 year and any allergic disease, including food allergy, atopic eczema, and/or atopic asthma, at age 4 years (aOR = 9.26; 95% CI, 2.46-34.85).
Reduced risks for allergic polysensitization, food allergy, atopic eczema and atopic wheeze by age 1 year were associated with higher proportions of cord blood nTreg. Also, larger household size had the most consistent association among the evaluated microbial factors with increased proportion of nTreg in cord blood at birth and with higher proportions of nTreg and aTreg during the first postnatal year.
Overall, the researchers concluded that there was an association between larger household size and higher nTreg proportions at birth and with higher nTreg and aTreg proportions through the first postnatal year.
However, these higher nTreg proportions at birth but not at 6 or 12 months predicted allergic outcomes by age 12 months, indicating that inadequate prenatal immune priming is important in allergic disease development.
Noting several features indicating possible causality, the researchers called for additional research should evaluate the immune priming role of previous pregnancies in the mother as well as the effects of the duration of labor.
Epigenetic studies should be included in studies of the prenatal programming of Treg cells as well, along with the influence of the maternal and infant gut microbiomes on the infant immune profile, the researchers added.
Perspective
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These findings are in line with previous observations that lower numbers of Tregs in the perinatal period are associated with an increased risk for allergic disease or allergic sensitization. What this study adds is household size as a potential correlate of Treg numbers in the perinatal period. Previous correlates of Treg numbers included birth into a farming environment, dog ownership and exposure to unpasteurized farm milk.
Many of the factors that correlate with reduced Treg numbers such as smaller family size and life in urban or suburban environments off the farm have been trends that have been prevalent across the industrial world over the last decades. These decades have seen a huge rise in the prevalence of allergic disease.
These differences seem to hold up when you compare society as a whole to more pre-industrial agrarian communities such as the Amish. On a day-to-day basis, I can’t say that I am able to see big differences in allergic disease correlating with family size, but I only see patients with allergic disease, not those who are unaffected.
Although it appears that Tregs may play an important role in preventing development of allergic disease, we know little beyond the correlations discussed above. I would be very reluctant to strongly recommend interventions, particularly something burdensome for a family such as taking on a new pet, moving to rural environment or exclusively breastfeeding for the first year based on correlation alone.
I will counsel families on what we know and save any strong recommendations for after we have evidence of the benefit of an intervention. For instance, although there has been some data that breastfeeding (and possibly exclusive or primary breastfeeding) may reduce the risk for allergic disease, the data are mixed, and it seems to be at most mildly protective. In contrast, there is very good evidence that early introduction of commonly allergenic foods is protective.
The next steps in this research first should be to confirm these studies in larger, more diverse populations (95% of the population in this study was of European descent), and other geographic locations. If the correlates hold up, investigators will need to design interventions to see if they affect allergic outcomes. This will be particularly challenging for factors such as household size.
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