Basic and clinical immunology
Sex-related differences in immune development and the expression of atopy in early childhood

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Background

Sex and age are known to influence the clinical expression of asthma and allergic diseases.

Objective

We sought to evaluate whether immune response profiles also vary by sex and age.

Methods

We performed a prospective birth cohort study (Childhood Origins of Asthma) designed to evaluate interactions among age, sex, immune responses, and virus infections on the development of asthma and allergic diseases. Two hundred eighty-nine subjects were enrolled at birth, and 275 maintained prospective follow-up for 3 years. Cytokine response profiles at birth, 1, and 3 years of age; rates of wheezing, atopic dermatitis, and viral illnesses; and biomarkers of atopy, including total and specific IgE levels and peripheral eosinophil counts, were evaluated.

Results

PHA-induced IFN-γ responses were higher in boys at 1 year of age (median, 35 vs 19 pg/mL; P < .001) and at 3 years of age (median, 282 vs 181 pg/mL; P = .07). Among children who wheezed during the third year of life, boys had increased IFN-γ, IL-5, and IL-13 responses at age 3 years (P < .001, P = .008, and P = .01, respectively). Boys also demonstrated increased rates of sensitization (P = .05 at year 1), total IgE levels (P = .03 at year 1 and P = .006 at year 3), and peripheral eosinophil counts (2.62 vs 1.85; P = .05 at year 3).

Conclusion

Sex-specific differences in immune responses develop during early childhood; some of these differences developmentally proceed, whereas others occur in parallel to the clinical expression of various atopic phenotypes.

Clinical implications

The differential expression of atopic diseases between boys and girls in early childhood is accompanied by sex-specific differences in immune response profiles.

Section snippets

Study subjects

After obtaining written informed consent, 289 subjects were enrolled at birth in the Childhood Origins of Asthma (COAST) study at a single research site beginning in November 1998 and ending in May 200016; 285 of these were followed prospectively for at least 1 year, and 275 had completed the evaluation at year 3. At least 1 parent was required to have demonstrable aeroallergen sensitization (defined as one or more positive skin test responses), a history of physician-diagnosed asthma, or both

Patient population

Two hundred eighty-nine children were enrolled at birth, with 275 having complete data at year 3. The prevalence of risk factors by sex is presented in Table I. Other than boys being slightly heavier at birth, there were no differences between boys and girls with respect to parental allergy or asthma, presence of furred pets in the home, passive smoke exposure, day-care attendance, or duration of breast-feeding.

Sex and developmental cytokine response patterns

Median PHA-induced IFN-γ responses were 84% higher in boys when compared with those

Discussion

Boys are more likely to have a number of atopic syndromes in early childhood, including atopic dermatitis, allergic sensitization, and wheezing. In addition to confirming these observations in a birth cohort at increased risk for atopic disorders, our results provide novel evidence of distinct patterns of cytokine responses in boys and girls over the first 3 years of life and indicate that the magnitude and direction of these response profiles differ, depending on the outcome measure being

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  • Cited by (0)

    Supported by National Institutes of Health grants 1R01HL61879-01 and 1P01HL70831-01.

    Disclosure of potential conflict of interest: R. F. Lemanske, Jr, has consultant arrangements with GlaxoSmithKline and AstraZeneca and is on the speakers' bureau for AstraZeneca, Aventis, Merck, and GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest.

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