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.

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)

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 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.

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.

[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.

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.

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.

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.

Prevalence of antinuclear antibodies in schoolchildren during puberty and possible relationship with musculoskeletal pain: a longitudinal study.

OBJECTIVE: The role of antinuclear antibodies (ANA) in children has still to be elucidated. The aim of our study was to evaluate the prevalence and persistence of ANA in schoolchildren during the puberty switch, and the possible relationship with chronic noninflammatory musculoskeletal pain (MSP). METHODS: Children aged 8-13 years and attending 4 public schools underwent a clinical examination, focusing on pubertal stage and presence of chronic noninflammatory MSP. Laboratory tests to determine the autoantibody-profile were also performed. Subjects with ANA positivity (titer ≥ 1:80) and/or chronic noninflammatory MSP were re-evaluated 3 years later. RESULTS: Two hundred sixty-one subjects enrolled in the study and 12.3% were ANA-positive, equally distributed in terms of sex and pubertal status. Three years later, in the group of patients studied for chronic noninflammatory MSP (n = 67), ANA positivity significantly increased from 13.4% to 44.8%. In the ANA-positive cohort at baseline (n = 28), 92.9% of subjects were confirmed as being ANA-positive with a significantly increased titer. No association between ANA positivity and chronic noninflammatory MSP was found. CONCLUSION: ANA prevalence and titers increase during puberty, especially in females, but have no relationship with chronic noninflammatory MSP. This finding may be related to the complex hormonal changes during the puberty switch period and opens new insights into autoimmunity.

Prenatal immune activation and subsequent peripubertal stress as a new model of schizophrenia.

Epidemiological studies show that maternal viral infection during pregnancy plays a key role in the etiology of neurodevelopmental disorders, such as schizophrenia and autism. Prenatal maternal immune activation and peripubertal psychological stress are key environmental risk factors for neurodevelopmental disorders. Viral mimic polyriboinosinic-polyribocytidylic acid is known to act as a Toll-like receptor-3 agonist. Polyriboinosinic-polyribocytidylic acid has been typically used to establish this rodent model of prenatal immune activation. Recently, Giovanoli et al. reported on a new neurodevelopmental model of schizophrenia based on combined prenatal immune activation and peripubertal stress. In this report, we place these findings into context and discuss their significance.

Comment on "Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice".

Giovanoli et al. (Reports, 1 March 2013, p. 1095) applied an immune challenge to pregnant females, and therefore to all offspring, and subsequently applied stress to offspring on a per cage basis. The data, however, were analyzed as a completely randomized design, which is inappropriate given these restrictions on randomization. This will increase both false positives and false negatives.

Response to comment on "Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice".

Lazic criticizes the statistical analyses used to support the conclusions in our mouse model. His theory-biased criticism is disproportionate in view of the robustness of our findings (even if different statistical methods are applied) and falls short in explaining the postpubertal onset of effects.

Stress in puberty unmasks latent neuropathological consequences of prenatal immune activation in mice.

Prenatal infection and exposure to traumatizing experiences during peripuberty have each been associated with increased risk for neuropsychiatric disorders. Evidence is lacking for the cumulative impact of such prenatal and postnatal environmental challenges on brain functions and vulnerability to psychiatric disease. Here, we show in a translational mouse model that combined exposure to prenatal immune challenge and peripubertal stress induces synergistic pathological effects on adult behavioral functions and neurochemistry. We further demonstrate that the prenatal insult markedly increases the vulnerability of the pubescent offspring to brain immune changes in response to stress. Our findings reveal interactions between two adverse environmental factors that have individually been associated with neuropsychiatric disease and support theories that mental illnesses with delayed onsets involve multiple environmental hits.

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.

[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.

A unifying hypothesis of schizophrenia: abnormal immune system development may help explain roles of prenatal hazards, post-pubertal onset, stress, genes, climate, infections, and brain dysfunction.

We propose a unifying hypothesis of schizophrenia to help reconcile findings from many different disciplines. This hypothesis proposes that schizophrenia often involves pre- or perinatal exposure to adverse factors that produce a latent immune vulnerability. When this vulnerability is manifested, beginning around puberty with changes in immune function and involution of the thymus, individuals become more susceptible to infections and immune dysfunctions that contribute to schizophrenia. Our hypothesis suggests theoretical bridges between different lines of evidence on schizophrenia and offers explanations for many puzzling findings about schizophrenia. For example, the hypothesis helps account for why schizophrenia patients tend to have had increased exposure to neurotropic infections, but most individuals with such exposure do not develop schizophrenia, and why prenatal hardships increase risk for schizophrenia, but the onset of symptoms typically does not occur until after puberty. The hypothesis also explains another paradox: lower socioeconomic status and poor prenatal care increase risk for schizophrenia at the same geographic site, but international comparisons indicate that countries with higher per capita incomes and better prenatal care actually tend to have higher schizophrenia prevalences. As the hypothesis predicts, (1) prenatal adversity, which increases risk for schizophrenia, also impairs post-pubertal immune competence, (2) schizophrenia patients experience elevated morbidity from infectious and auto-immune diseases, (3) genetic and environmental risk factors for schizophrenia increase vulnerability to these diseases, (4) factors that exacerbate schizophrenic symptoms also tend to impair immune function, (5) many anti-psychotic medications combat infection, (6) effects of early infections may not appear until after puberty, when they can produce neurologic and psychiatric symptoms, and (7) immune dysfunctions, such as imbalances of pro- and anti-inflammatory cytokines, may contribute to the onset of psychotic symptoms and the progressive loss of brain tissue in schizophrenia. The disruptive effects of prenatal adversity on the development of the immune system may often combine with adverse effects on prenatal brain development to produce schizophrenia. This paper focuses on the adverse immune system effects, because effects on the brain have been extensively discussed in neurodevelopmental theories of schizophrenia. We propose new tests of scientific predictions. We also point out potential clinical implications of the hypothesis; for example, individuals with schizophrenia may often have underlying infections or immune dysfunctions, such as imbalances in inflammatory cytokines, that contribute to the illness. This possibility could be tested experimentally--e.g., by clinical trials in which patients' exposure to infection is reduced or immune function is normalized.

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.