User login
Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.
The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).
A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).
Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.
“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.
Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.
Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.
The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).
A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).
Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.
“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.
Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.
Although related by their European origins in neighboring countries and similar cultural lifestyles, the immune profiles and prevalences of asthma and allergic sensitization differ between Amish and Hutterite school children, according to the results of a study published in the New England Journal of Medicine.
The predominant differences between the Amish and Hutterite populations today are region of concentration (Indiana and South Dakota, respectively) and agrarian style (traditional and industrialized farming, respectively). First author Michelle M. Stein of the University of Chicago and her colleagues conducted a study of 30 Amish age- and sex-matched children (aged 7-14 years) living in Indiana and 30 Hutterite children living in South Dakota during the months of November and December, respectively. Immune profile–related variables examined included levels of common allergens and endotoxins detectable in airborne dust, percentages of total peripheral blood leukocytes, cell-surface markers on neutrophils and monocytes, cytokine levels from peripheral-blood leukocytes with or without innate or adaptive stimuli, and gene expression levels from peripheral-blood leukocytes. In additional experiments using a murine model of experimental allergic asthma, house dust from Amish and Hutterite homes was administered intranasally to mice for 4-5 weeks to gauge their immune responses (N Engl J Med. 2016;375:411-21).
A genetic analysis revealed that the two populations shared a closer genetic relationship with each other than with populations from other countries in Europe. The study results also confirmed the known differences between the Amish and Hutterite prevalences of asthma (0% vs. 20%, respectively) and positivity for allergen-specific IgE (17% vs. 30% and 7% vs. 30% using cutoffs of greater than 0.7 and greater than 3.5 kUA/L, respectively). Also, median levels of endotoxins were found to be almost sevenfold greater in Amish homes (4,399 endotoxin units [EU] per square meter vs. 648 EU per square meter, P less than .001).
Compared with results generated using Hutterite peripheral-blood leukocytes, increased proportions of neutrophils, decreased proportions of eosinophils, and similar proportions of monocytes were observed in the Amish. In addition to proportional differences, the phenotypes of the neutrophils from the Amish children also differed by expressing lower levels of the chemokine receptor CXCR4 and the adhesion molecules CD11b and CD11c. The phenotypes of the monocytes differed as well, showing a suppressive phenotype in the Amish children. A specific network of differentially expressed innate immune genes in untreated peripheral-blood leukocytes was found to be associated with the observed differences in the relative amounts of neutrophils, eosinophils, and monocytes, as well as their phenotypes. The median levels of all 23 cytokines detected in peripheral-blood leukocytes following innate stimulation differed between the populations and showed lower levels among the Amish children (P less than .001). Adaptive stimulation, however, did not lead to differences in cytokine levels between the two groups. The results from the murine model indicated that exposure to the Amish conditions was associated with innate immune responses consistent with protective effects against asthma. Collectively, these results strongly suggest that the Amish environment affords protection against asthma via innate immune system signaling.
“A deeper understanding of the relevant stimuli and the innate immune pathways they engage may ultimately pave the way for the development of effective strategies for the prevention of asthma,” wrote Ms. Stein and her colleagues.
Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.
Key clinical point: The innate immune responses and prevalences of asthma and allergic sensitization differ between populations of school children with similar regional and genetic origins and cultures.
Major finding: The two populations were highly genetically similar, but expressed a variety of differences in their immune profiles suggestive of enhanced immunity in the Amish, possibly attributable to differential allergen exposure.
Data sources: Sixty children (30 Amish, 30 Hutterite) were matched for age and sex. A murine model of experimental allergic asthma also was employed.
Disclosures: Funding for this project was provided by the National Institutes of Health, St. Vincent Foundation, and the American Academy of Allergy, Asthma, and Immunology Foundation. Several study authors disclosed grant support from the NIH; one received support from the European Research Council and the German Research Foundation; and several disclosed ties to industry sources.
