Do gender and puberty influence allergic diseases?

Differences between biological sex, gender identity, and their impact on health may have significant implications for the prevention, screening, diagnosis, and treatment of several diseases, including allergies. Asthma, allergic rhinitis (AR), atopic dermatitis (AD), and allergic conjunctivitis (AC) have different prevalences and different risk factors in infancy. Although boys present allergies more often in childhood, it quickly changes during girls' sexual development, leading to lifelong female predominance of allergic diseases. This can be explained by the influence of sexual hormones, different lifestyles adopted by men and women, microbiota diversity, diet distinctions, professional options, and adherence to treatment, among others. Gender-related aspects should become essential parameters in allergology to diagnostic and therapeutic stratification, associated with molecular, genetic, and epigenetic patterns. Longitudinal studies would be interesting to evaluate possible mechanisms underlying these differences in prevalence. Sex- and gender-specific observations beyond 14 years of age are scarce and further allergic multimorbidity studies in different populations, especially in adults, are necessary.

Pubertal Status and Age are Differentially Associated with Inflammatory Biomarkers in Female and Male Adolescents.

A better understanding of the maturational correlates of inflammatory activity during adolescence is needed to more appropriately study both normal and abnormal development. Inflammation is the immune system's first response to infection, injury, or psychological stress, and it has been shown to be elevated in individuals with both physical and psychological conditions. This study examined unique associations between (1) pubertal status and inflammatory biomarkers, and (2) age and inflammatory biomarkers, and whether these relationships differed by sex in a diverse sample of 155 adolescents (54.2% female, 45.8% male; Mage = 16.22) from a northeastern city in the US. A more advanced pubertal status was uniquely associated with lower levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). Chronological age was uniquely associated with lower IL-8 levels. The association between pubertal status and C-reactive protein (CRP) levels differed by sex: more mature females had higher CRP, whereas pubertal status and CRP were not significantly associated in males. These findings highlight an important relation between pubertal development and inflammatory activity during adolescence.

The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.

BACKGROUND: Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. METHODS: In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. FINDINGS: We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. INTERPRETATION: The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.

[ON THE ISSUE OF AUTOIMMUNE OVARY DAMAGE DURING PUBERTY].

The aim of the study was to ascertain the influence of AІТ on the formation of autoimmune damage to ovaries by determining the connections between the levels of AOAB, ATPO, gonadotropic and sex hormone levels, and the functional state of the ovaries and thyroid gland. 198 girls age 10-18 were studied: 166 with AIT (AIT+ Group), и 32- without AIT (the AIT- Group). A defined difference between TTH. and ATPO, was revealed, which is explained by the presence of thyroid pathology in the AIT+ Group. Prolactin levels and ovarian volume were notably higher, while Progesterone levels were lower in the AIT+ Group. No discernable differences among levels of AOAB, sex hormones, Estrogen, Testosterone or antral follicules were observed. A direct correlation was revealed between AOAB levels and the girls' age both in the AIT+ and AIT- groups. AOAB data was divided into three tertials in order to study links with various hormonal homeostasis. Analysis of data obtained showed numerous correlative links between ATPO, AOAB, gonadotropins, sex hormones, TTH and ovarian volume in all tertials of both the AIT+ and AIT- groups; correlative links were found, too, between AOAB and ATPO in the III tertial groups AIT+ and AIT-. In adolescents with AIT disbalance occurs at all levels of hormonal homeostasis as well as in ovarian structure. Such changes and the presence of ATPO and AOAB may be associated with emerging autoimmune ovary damage.

Prospective evaluation of risk factors for the development of islet autoimmunity and type 1 diabetes during puberty--TEENDIAB: study design.

Type 1 diabetes (T1D) has a peak incidence in childhood and adolescence. The TEENDIAB study investigates the period of puberty and adolescence in the natural course of T1D development. Evidence suggests that the immune phenotype of children developing autoimmunity during puberty and adolescence differs from that in childhood. We hypothesize that these differences reflect heterogeneity in the genetic and environmental factors that influence the development of autoimmunity in puberty versus early infancy. TEENDIAB is an observational cohort study that enrols and follows 1500 children aged 8-12 and who have a first degree relative with T1D to test this hypothesis. Data collection and analyses will focus on determining the phenotype of islet autoimmunity, genotypes of T1D- and type 2 diabetes-associated genes, insulin resistance, and ß-cell function, growth, obesity, and physical exercise. The findings of this study will increase the understanding of pathogenetic mechanisms behind the increasing diabetes incidence in youth and the impact of obesity on diabetes development in this age period.

Heterozygosity of the major histocompatibility complex predicts later self-reported pubertal maturation in men.

Individual variation in the age of pubertal onset is linked to physical and mental health, yet the factors underlying this variation are poorly understood. Life history theory predicts that individuals at higher risk of mortality due to extrinsic causes such as infectious disease should sexually mature and reproduce earlier, whereas those at lower risk can delay puberty and continue to invest resources in somatic growth. We examined relationships between a genetic predictor of infectious disease resistance, heterozygosity of the major histocompatibility complex (MHC), referred to as the human leukocyte antigen (HLA) gene in humans, and self-reported pubertal timing. In a combined sample of men from Canada (n = 137) and the United States (n = 43), MHC heterozygosity predicted later self-reported pubertal development. These findings suggest a genetic trade-off between immunocompetence and sexual maturation in human males.

[Flow cytometry application in the evaluation of antisperm antibodies in sera samples of infertile people and prepubertal boys with gonadal disorders]. / Wykorzystanie cytometrii przeplywowej do oceny wystepowania przeclwcial przeciwplemnikowych w surowicy od nieplodnych osób doroslych i chlopców przed pokwitaniem z wadami w drogachi rozrodczych.

OBJECTIVES: The aim of the following study was to assess antisperm antibodies in sera samples of infertile men and women, as well as from prepubertal boys by means of flow cytometry. MATERIAL AND METHODS: We tested sera samples of infertile and fertile adult populations, prepubertal boys with gonadal disorders and healthy prepubertal boys. The indirect immunobead test and flow cytometry were used to detect antisperm antibodies. RESULTS: The comparison of antisperm antibody levels in sera samples of adult infertile versus healthy controls (men and women) evaluated by means of flow cytometry did not reveal statistically significant differences. The only significant correlation found were results obtained by IDIBT and FCM for IgG antisperm antibodies for infertile adult group (r = 0.507, p = 0.012). The comparison of antisperm antibody levels in sera samples from prepubertal boys revealed statistically significant differences for all tested antibody isotypes. Diagnostic values compared for both assays showed markedly better discriminatory ability of flow cytometry for analyzed groups of prepubertal boys than for adult populations. CONCLUSIONS: Flow cytometry test may be used to verify antisperm antibody levels in prepubertal boys with testicular failures.

Pubertal development and premature ovarian insufficiency in patients with APECED.

OBJECTIVE: To determine the natural course of pubertal development, growth during puberty, and development of POI in females with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), also called autoimmune polyendocrine syndrome type I. DESIGN: Longitudinal follow-up study. METHODS: A national cohort of females with APECED aged ≥12 years were followed during 1965-2018. Attainment of adult height was defined when patients' height increased less than 1 cm per year. Diagnosis of POI was based on delayed puberty or POI symptoms with amenorrhea, and/or FSH ≥40 IU/L. RESULTS: Altogether 40 women with APECED were followed up to the average age of 37.3 (range: 14.6-61.9) years; 16 females (40%) were ≥ 40 years. Pubertal development started spontaneously in 34 patients and 29 had spontaneous menarche. POI developed in 28 patients (70%) at the median age of 16.0 years (range: 11.3-36.5), and in 20 of them (71%) before attaining adult height. In 11 cases puberty was induced or completed by hormonal therapy. Patients with POI were significantly shorter at menarche, but adult heights did not differ from non-POI females. Patients with POI had more often primary adrenocortical insufficiency (93% vs 58%, P = 0.017) and ovarian antibodies (81% vs 30%, P=0.003) compared to those with normal ovarian function (n = 12). CONCLUSIONS: POI developed in the majority of patients with APECED, often before or shortly after menarche. Timely commencement of hormonal replacement therapy is important to ensure optimal pubertal development and growth. The possibility of fertility preservation before development of POI in APECED patients should be further studied.

The changes in the T-lymphocyte subsets in a population of Turkish children with puberty gingivitis.

OBJECTIVE: The aim of the study was to investigate the number of CD4 and CD8 T lymphocytes, analyse subjects with gingivitis and those without, and determine the role of T lymphocytes in the pathobiology of puberty gingivitis. MATERIAL AND METHODS: Fifty individuals with and without puberty gingivitis were recruited for this study. The CD4(+) and CD8(+) T-lymphocyte counts were determined using flow cytometry on the biopsy samples, and the CD4(+)/CD8(+) ratio was calculated. At the same time, periodontal index scores were recorded to assess the periodontal status. Acquired data were analysed statistically using a paired t-test to compare laboratory values obtained before and after the treatment in individuals with puberty gingivitis and disease-free individuals. In addition, Pearson's correlation analysis was performed to investigate the relation between laboratory values and clinical measurements. RESULTS: The CD4(+)/CD8 ratio in gingival tissues obtained from test group was significantly higher (P < 0.05) than that found in the gingival tissue obtained from control group. We found that the CD4(+) and CD8(+) lymphocyte counts continued to increase significantly (P < 0.001) and the CD4(+)/CD8(+) ratio continued to drop significantly (P < 0.05) after treatment in test group. CONCLUSIONS: T lymphocytes could play a significant role in the pathobiology of puberty gingivitis.

Age-associated remodeling of thymopoiesis: role for gonadal hormones and catecholamines.

The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered.

Sex Bias in Asthma Prevalence and Pathogenesis.

Sex-related differences in asthma prevalence are well established and change through the reproductive phases of life. As children, boys have increased prevalence of asthma compared to girls. However, as adults, women have increased prevalence of asthma compared to men. Many factors, including genetics, environment, immunological responses, and sex hormones, affect the sex disparity associated with the development and control of asthma and other allergic diseases. Fluctuations of hormones during puberty, menstruation, pregnancy, and menopause, alter asthma symptoms and severity. In this article, we review clinical and epidemiological studies that examined the sex disparity in asthma and other allergic diseases as well as the role of sex hormones on asthma pathogenesis.

Gender differences in asthma development and progression.

BACKGROUND: Asthma is a chronic inflammatory airway disease that has a higher prevalence in boys than in girls before puberty and a higher prevalence in women than in men in adulthood. Because of the complexity of the disease, no single straightforward mechanism can explain the gender differences found in asthma. OBJECTIVE: This article reviews the effects of sex on the development and outcome of atopy and asthma. METHODS: English-language articles were identified by a PubMed database search from 1980 to 2007 using the terms asthma, gender, sex, hormones, and lung development. RESULTS: It is likely that hormonal changes and genetic susceptibility both contribute to the change in prevalence that occurs about the time of puberty. Severe asthma is also more predominant in females. In adulthood, women are more susceptible to the effects of smoking and more likely to develop asthma. CONCLUSIONS: It is important to determine whether asthma is a social, cultural, hormonal, and/or genetic issue. A number of topics on gender differences in asthma development and progression require additional research. For example, the interaction of fetal lung development and hormonal factors needs to be studied because it has consequences throughout life. Genetic studies of asthma should be stratified by sex, because some polymorphisms are particularly related to asthma in females. Further studies should be conducted on hormone-gene interactions (eg, X-chromosome genes) in relation to asthma and atopy. In addition, cellular hormonal influences in asthma and atopy in relation to innate and acquired immunity in both sexes need to be examined. This would benefit patients not only with asthma but also with many other diseases that show gender differences in prevalence, severity, and treatment response. Animal models investigating observed gender differences in humans should focus on susceptibility to environmental and hormonal factors in relation to lung and immune development. Differences in treatment response in asthma need to be examined as well. Double-blind studies need to be stratified by sex, and treatment responses in females and males should be investigated separately. Furthermore, interaction between gender and behavioral change in relation to asthma development and management should be studied.

Do gender and puberty influence allergic diseases?

Differences between biological sex, gender identity, and their impact on health may have significant implications for the prevention, screening, diagnosis, and treatment of several diseases, including allergies. Asthma, allergic rhinitis (AR), atopic dermatitis (AD), and allergic conjunctivitis (AC) have different prevalences and different risk factors in infancy. Although boys present allergies more often in childhood, it quickly changes during girls’ sexual development, leading to lifelong female predominance of allergic diseases. This can be explained by the influence of sexual hormones, different lifestyles adopted by men and women, microbiota diversity, diet distinctions, professional options, and adherence to treatment, among others. Gender-related aspects should become essential parameters in allergology to diagnostic and therapeutic stratification, associated with molecular, genetic, and epigenetic patterns. Longitudinal studies would be interesting to evaluate possible mechanisms underlying these differences in prevalence. Sex- and gender-specific observations beyond 14 years of age are scarce and further allergic multimorbidity studies in different populations, especially in adults, are necessary (AU)

Breast inflammatory gigantomastia in a context of immune-mediated diseases.

CONTEXT: Localized breast lesions have been described in lupic or diabetic patients. However, the description of breast gigantomastia in women presenting with autoimmune diseases has not been reported. SETTING: The study took place within the Department of Endocrinology and Reproductive Medicine, Necker Hospital, Paris, France. PATIENTS: We describe eight patients with inflammatory gigantomastia, occurring in a context of immune-mediated diseases: myasthenia, chronic arthritis, or thyroiditis. MAIN OUTCOME MEASURES: Together with hormonal, immunological, and breast magnetic resonance imaging (MRI) evaluation, breast histology enabled us to perform immunocytochemical and indirect immunofluorescence studies. Control sera were obtained from patients with (n = 10) and without (n = 7) antinuclear antibodies. RESULTS: Six of the eight patients developed gigantomastia either at puberty or during pregnancy. Neither a hormonal oversecretion nor a specific immunological pattern was observed. All patients except one presented antinuclear antibodies. Histological study revealed a diffuse, stromal hyperplasia and a severe atrophy of the lobules. A rarefaction of adipocytes was also noted, as previously suggested on MRI. There was a perilobular lymphocytic infiltrate made of CD3+ lymphocytes. Study of sera from five of six cases of gigantomastia showed a nuclear immunofluorescence pattern in normal mammary ductal and lobular glandular epithelium, as well as in kidney and intestine epithelial cells. In control sera, a nuclear signal was observed only when antinuclear antibodies were present. CONCLUSIONS: We suggest that breast tissue may be a target tissue in autoimmune diseases, this process being favored by the hormonal milieu. However, the precise mechanism of such association is not individualized. The fact that stromal hyperplasia is the main histological feature justifies the search for the involvement of growth factors in such a process.

Dendritic cells change IL-27 production pattern during childhood.

BACKGROUND: Interleukin-27 (IL-27) has been described to be highly expressed during the very first days after birth, but secretion of IL-27 by dendritic cells during the course of childhood has not been described. FINDINGS: In our present study we enrolled children (n = 55) in the range from 1 day of to 18 years of age and asked for a small whole blood sample. The capacity of dendritic cells to produce IL-27 during childhood was measured after whole blood culture with or without inflammatory stimuli. Results support recent findings of high IL-27 levels after birth and lowest levels in adults. Interestingly, we detected an interim peak production level at early adolescence. CONCLUSION: These data hint to prominent roles of IL-27 at the very start of post-natal life. Furthermore, a link has been given to so far not described immunological events during puberty.

Hypophyseal-pituitary-adrenal axis in autoimmune and rheumatic diseases.

This article discusses the effects of sex steroids and anterior pituitary hormones on the immune system. Data from clinical and experimental studies on the effects of CRH, FSH, LH, and prolactin are reviewed. This is followed by a summary of results from our studies on the effects of FSH, LH, and prolactin on PBMC, CD4+ cells, and CD8+ cells in vitro.

Rheumatoid arthritis: are pets implicated in its etiology?

Rheumatoid arthritis (RA) is thought to be triggered by an environmental agent or agents in immunogenetically predisposed persons. To investigate if animals or animal products might be the disease reservoir for a putative environmental trigger for RA that acts in childhood, a case-control study was undertaken. Included were 122 cases of RA and 114 control subjects of similar age. A specifically trained assistant, blinded to the diagnosis, used a standard interview proforma to gather information on ages of exposure to agents before onset of symptoms. Univariate analysis showed that cases were significantly more likely to have had a close association with a cat in the prepubertal period (65%) than were controls (27%); odds ratio (OR), 4.9 (confidence interval [CI] 2.7 to 9.0). In addition, there was a dose-response relationship between extent of prior exposure to cats and RA. There was a weaker association between recalled prior exposure to birds, budgerigars (parakeets) in particular, and RA. These data suggest that certain pets may be the reservoirs for environmental agents that trigger RA after a period of latency.

Mucosal immunity of the adolescent female genital tract.

This study sought to characterize mucosal immunity of the adolescent genital tract during the cycle and determine if adolescents have more suppressed immunoglobulin levels in the follicular phase than adults. Daily from cycle day 9 until ovulation, then every other day until menses, cervical secretions for IgA, IgG, and cytokines were collected via Weck-Cel sponge and serum for luteinizing hormone (LH), estradiol, and progesterone was obtained from three adolescent girls (mean age 16.8 years). Immunoglobulin and cytokine levels varied during the menstrual cycle, reaching their nadir around ovulation. Compared with 13 adults, adolescents had a greater drop in IgG in the follicular phase (mean beta-953 vs. -269 microg/mL/day, p = .045), but a similar rate of rise in IgG in the luteal phase (mean beta +118 vs. +100 microg/mL/day, p = .252). Rates of change in IgA did not differ between adolescents and adults for either phase. Although limited by the small sample size, these findings suggest that adolescents may be more sensitive to unopposed estrogen and warrant further investigation.

[Local anti-infective protection of the reproductive tract in women of different ages]. / Mestnaia protivoinfektsionnaia zashchita reproduktivnogo trakta zhenshchin razlichnogo vozrasta.

Healthy girls and women of the reproductive age, as well as women immediately before and after menopause, were examined. Neutrophils and immunoglobulins of cervical and vaginal secretions were studied and, as a result, age-dependent differences in the activity of the anti-infectious protection of the reproductive tract of women were found.