Allergic disease in 8‐year‐old children is preceded by delayed B cell maturation

Strömbeck, Anna; Nordström, Inger; Andersson, Kerstin; Andersson, Helén; Johansen, Susanne; Maglio, Cristina; Rabe, Hardis; Adlerberth, Ingegerd; Wold, Agnes E.; Hesselmar, Bill; Rudin, Anna; Lundell, Anna‐Carin

doi:10.1111/cea.12922

Cited by 9 publications

(16 citation statements)

References 43 publications

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“…Testosterone has been shown to directly inhibit antibody production [ 170 ] and prevent B cell maturation [ 171 , 172 ]. These effects and an early surge in testosterone in males following birth may provide an explanation why young boys display lower proportions of mature B cells [ 173 ], which has also been associated with an increased risk of developing allergic disease and IgE sensitization, compared to pre-puberty girls [ 174 ].…”

Section: Respiratory Allergic Sensitisation: the Mechanisms In Rodmentioning

confidence: 99%

Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females

Leffler

Stumbles

Strickland

2018

IJMS

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IgE sensitisation has increased significantly over the last decades and is a crucial factor in the development of allergic diseases. IgE antibodies are produced by B cells through the process of antigen presentation by dendritic cells, subsequent differentiation of CD4+ Th2 cells, and class switching in B cells. However, many of the factors regulating these processes remain unclear. These processes affect males and females differently, resulting in a significantly higher prevalence of IgE sensitisation in males compared to females from an early age. Before the onset of puberty, this increased prevalence of IgE sensitisation is also associated with a higher prevalence of clinical symptoms in males; however, after puberty, females experience a surge in the incidence of allergic symptoms. This is particularly apparent in allergic asthma, but also in other allergic diseases such as food and contact allergies. This has been partly attributed to the pro- versus anti-allergic effects of female versus male sex hormones; however, it remains unclear how the expression of sex hormones translates IgE sensitisation into clinical symptoms. In this review, we describe the recent epidemiological findings on IgE sensitisation in male and females and discuss recent mechanistic studies casting further light on how the expression of sex hormones may influence the innate and adaptive immune system at mucosal surfaces and how sex hormones may be involved in translating IgE sensitisation into clinical manifestations.

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Section: Respiratory Allergic Sensitisation: the Mechanisms In Rodmentioning

confidence: 99%

Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females

Leffler

Stumbles

Strickland

2018

IJMS

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“…Infant serum EPA levels, in turn, correlated negatively with the risk of being allergic at 3 years of age [ 16 ]. We have also shown in the same cohort that high proportions of circulating FOXP3 + CD25 high CD4 + T cells, suggestedly representing regulatory T cells, at birth are positively associated with being sensitized later in childhood [ 17 ] and that infants with a high proportion of CD5 + B cells at birth and during the first month of life are at increased risk for allergy development [ 18 , 19 ]. CD5 + B cells were mostly found to be so-called “transitional B cells”, i.e., B cells that were recently produced in the bone marrow and that had not yet undergone full maturation to become mature naïve B cells [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Cord Blood Levels of EPA, a Marker of Fish Intake, Correlate with Infants’ T- and B-Lymphocyte Phenotypes and Risk for Allergic Disease

et al. 2020

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Maternal fish intake during pregnancy has been associated with reduced allergy development in the offspring and here, we hypothesized that components of fish stimulate fetal immune maturation. The aim of this study was to investigate how maternal fish intake during pregnancy and levels of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the infant’s cord serum correlated with different subsets of B- and T-cells in cord blood and B-cell activating factor (BAFF) in cord plasma, and with doctor-diagnosed allergy at 3 and 8 years of age in the FARMFLORA birth-cohort consisting of 65 families. Principal component analysis showed that infant allergies at 3 or 8 years of age were negatively associated with the proportions of n-3 LCPUFAs (eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) in infant cord serum, which, in turn correlated positively with maternal fish intake during pregnancy. Both maternal fish intake and cord serum n-3 LCPUFAs correlated negatively to CD5+ B cells and the FOXP3+CD25high of the CD4+ T cell subsets in cord blood, but not to BAFF in cord plasma. Our observational study suggests that fish might contain components that promote maturation of the infant’s immune system in a manner that protects against allergy development.

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“…In conclusion, the present results suggest that DHT in utero might be involved in the mechanism that leads to higher proportions of circulating immature/naïve B cells and higher fractions of Tregs in boys compared to girls. We have previously demonstrated that a high proportion of CD5 + B cells in the first month of life is a risk factor for development of IgE-mediated allergic disease up to 8 years of age 29 , 33 , but it remains to be investigated if sex-related differences concerning steroid hormones and certain immune variables in early life influence development of autoimmune and infectious disease later in life.…”

Section: Discussionmentioning

confidence: 99%

“…In the prospective FARMFLORA study, farming and non-farming families from rural areas in the Skaraborg region in South-West Sweden were enrolled at maternity care clinics. Sixty-five healthy infants born at term (33 boys and 32 girls, median gestational age at delivery: boys 279 days and range 254–297 days, girls 279 days and range 254–298 days) were included in the study and have previously been followed in detail with respect to adaptive immune maturation up to 8 years of age 4 , 7 , 28 , 29 . In the 8-year follow-up study, 48 children participated (23 boys and 25 girls; median age boys: 7.9 years, range 6.8–9.1 and girls: 8.3 years, range 6.4–9.3).…”

Section: Methodsmentioning

confidence: 99%

“…All blood samples were collected in preservative-free heparin tubes. Allergic disease at 8 years of age was clinically evaluated for all children by a pediatrician as previously described in detail 29 and also presented in Table 1 . Immunization data regarding DTP and MMR vaccine-specific antibody plasma titers from children whose parents agreed to take part in this specific part of the study are presented in previous publications 3 , 4 and in Table 1 .…”

Section: Methodsmentioning

confidence: 99%

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Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys

Lundell

Nordström

Andersson

et al. 2017

Sci Rep

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Boys present with higher proportions of immature/naïve CD5+ B cells than girls up to 3 years of age. Boys also have higher fractions of regulatory T cells (Tregs) in early infancy, but the mechanisms for these sex-related differences are unknown. In the prospective FARMFLORA follow-up study of 23 boys and 25 girls, we investigated if these immunological differences remained at 8 years of age. We also examined if testosterone or dihydrotestosterone (DHT) levels at birth and at 8 years of age were associated with immune maturation. Immunological variables and androgen levels were examined and measured in blood samples obtained at birth, 3–5 days and at 8 years of age. Boys had higher proportions of CD5+ and immature/transitional CD24hiCD38hi B cells, whereas girls had higher fractions of B cells with a memory phenotype at 8 years of age. School-aged boys also presented with higher frequencies of Tregs, and a greater capacity to produce T-cell-associated cytokines. Among boys, higher cord blood DHT levels were associated with higher proportions of CD5+ B cells in early infancy and at 8 years of life. These results suggest that DHT actions in utero might be involved in the mechanism for delayed peripheral B-cell maturation in boys.

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Allergic disease in 8‐year‐old children is preceded by delayed B cell maturation

Abstract: High proportions of neonatal naïve B cells remained as a risk factor for allergic disease in school-aged children. Thus, the accelerated B cell maturation observed among farmers' children may be crucial for the allergy-protective effect of a farming environment.

Cited by 9 publications

References 43 publications

Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females

Immunological Processes Driving IgE Sensitisation and Disease Development in Males and Females

Cord Blood Levels of EPA, a Marker of Fish Intake, Correlate with Infants’ T- and B-Lymphocyte Phenotypes and Risk for Allergic Disease

Dihydrotestosterone levels at birth associate positively with higher proportions of circulating immature/naïve CD5+ B cells in boys

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