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Context: Exercise immunology is aimed at understanding how exercise sessions can affect the immune system in athletic subjects of different age groups. The objective of the current study was to discuss in which stage of biological maturation (BM) young athletes may be more vulnerable in relation to the immune system, and whether there is a BM range in which it is safer to perform sports training with strenuous exercise loads., Evidence Acquisition: Evidence from scientific research from several scientific disciplines (eg, immunology, sport immunology, pediatrics, sports medicine, human development) was gathered to holistically examine the main particularities of exercise immunology as applied to pediatric sport., Study Design: Narrative review., Level of Evidence: Level 5., Results: In pediatric patients, lymphoid tissue expands during puberty and involutes after puberty until it returns to pre-expansion values. This suggests that there is a specific period in which the immune system may be stronger, which may provide opportunities for strenuous exercise in pediatric athletes. However, the chronological period when puberty occurs will be determined by BM, which is the rate at which the biological systems of the human body improves. This may affect the period of lymphoid tissue expansion and, consequently, the behavior of the immune system in pediatric subjects of the same age category., Conclusion: During puberty, there is a significant increase in the proinflammatory profile; to compensate for this, there is an expansion of lymphoid tissue that may favor the efficiency of the immune system. The period in which puberty is reached may vary according to the stages of BM. Therefore, in exercise immunology applied to pediatric sports, in addition to external and internal training loads, it is necessary to consider BM and puberty, which have been shown to be safer biomarkers than chronological age for determining immune system behavior in pediatric athletes., Strength-Of-Recommendation Taxonomy (sort): Evidence B level 3., Competing Interests: The authors report no potential conflicts of interest in the development and publication of this article.

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., (© 2021. The Author(s).)

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., Competing Interests: All the authors have nothing to disclose related to this article. The content of the manuscript has not been published or submitted for publication elsewhere.We confirm that this work is original and has not been published elsewhere. All authors have conceived and planned the project, as well as analyzed and interpreted the data. We all have organized and critically reviewed the manuscript’s content and approved the final content.

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.

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; M age  = 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.

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 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.

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., (© 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.)

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.

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.

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.

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.

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.

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.

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 β-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., (© 2011 John Wiley & Sons A/S.)

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.

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., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

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.

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., (Copyright 2008 S. Karger AG, Basel.)

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.

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.

Aims: To investigate the natural history and incidence of autoimmune thyroiditis (AIT) in paediatric patients with type 1 diabetes (T1D)., Methods: Since 1990, annual screening for thyroid disease has been performed in children and adolescents with T1D. Antibodies against thyroperoxidase (anti-TPO) and thyroglobulin (anti-TG) as well as TSH were measured in 659 patients (54.3% boys). In 126 patients, anti-TPO and anti-TG levels were followed at yearly intervals from onset up to five years of T1D. Anti-TPO above 30 U/ml and anti-TG above 20 U/ml were considered positive, values above 100 U/ml as significantly raised and indicative of AIT. L-thyroxine treatment was started if TSH was higher than 4.5 microU/ml and/or thyroid gland enlargement on thyroid ultrasound was present., Results: At initial screening, 15.4% of patients had raised anti-TPO and 14.4% anti-TG. Girls had more frequently raised antibodies than boys. Sixty two patients (9.4%, 61% girls) required treatment with L-thyroxine. The cumulative incidence (SE) of AIT after 10 years of diabetes was 0.14 (0.02), being significantly higher in females (0.18 (0.03)), particularly after the age of 12 years. At T1D onset, positive anti-TPO and anti-TG were present in 21 of 126 patients (16.7%), each. All patients with significantly increased values of anti-TPO (n = 17, 148-5340 U/ml) and anti-TG (n = 11, 140-2000 U/ml) at T1D onset remained positive during the following five years., Conclusions: For early detection of autoimmune thyroiditis in children with T1D, measurement of anti-TPO and TSH at T1D onset and in yearly intervals after the age of 12 years is recommended.

Purpose: We investigated serum antisperm surface antibody (ASA) prevalence at puberty, which is reported to be as high as 38% in the sera of males with cryptorchidism operated on before puberty. Operative technique impact, dartos pouch orchiopexy or testis fixation, was also examined., Materials and Methods: We examined a total of 61 pubertal males (Tanner stage 2 or greater) divided into 3 groups. Group 1 consisted of 24 males with cryptorchidism 10 to 17.9 years old who underwent unilateral dartos pouch orchiopexy before puberty (median age 5.85). All of these cases were known to be negative for ASA preoperatively, and 20 before puberty. Group 2 consisted of 22 males with cryptorchidism 12.1 to 17.7 years old operated on previously (median age 10.35) by testicular fixation among other techniques. Group 3 consisted of 15 healthy males 12.2 to 17.3 years old. Prepubertal ASA status was unknown for groups 2 and 3. Operated testis was compared with counterpart before serum collection in group 1 and during operation in group 2. IgG IgM and IgA ASA were studied by the indirect Immunobead (BioRad, Clinisciences S.A., Montrouge, France) test., Results: All sera tested were found negative in the 3 groups. Dartos pouch operation, testis fixation or even consecutive operations did not induce ASA production. Alterations in size or consistency were observed in operated testes in 10 patients in group 1, and in 8 patients in group 2., Conclusions: Our results suggest that dartos pouch orchiopexy, testicular fixation and/or intrinsic developmental alterations of the cryptorchid testis does not elicit an autoimmune response against sperm surface antigens at puberty.

In areas where Plasmodium falciparum malaria is endemic, parasite density, morbidity, and mortality decrease with increasing age, which supports the view that years of cumulative exposure are necessary for the expression of maximal protective immunity. Developmental changes in the host also have been implicated in the expression of maximal resistance. To further evaluate the contribution of host developmental factors in malaria resistance, we examined the relationship between P. falciparum parasitemia and pubertal development in a cross-sectional sample of 12-18-year-old schoolgirls from an area of intense transmission in western Kenya. Among pubertal girls, dehydroepiandrosterone sulfate (DHEAS) levels were significantly associated with decreased parasite density, even after adjustment for age. DHEAS levels also were related to increased hemoglobin levels, even after accounting for age and other determinants of hemoglobin level. These findings support the hypothesis that host pubertal development, independent of age and, by proxy, cumulative exposure, is necessary for maximal expression of resistance to malarial infection and morbidity, as assessed by hemoglobin level.

In order to assess the effects of age-related changes of serum dehydroepiandrosterone sulphate (DHEAS) and androstenediol (AED) concentrations on BCG vaccination throughout the puberty period, we matched 41 prepubertal (mean age 8.63 +/- 1.36 years, range 8-14 years) and 43 pubertal (mean age 13.8 +/- 1.31 years, range 10-16 years) schoolchildren who were PPD negative and free of disease or medication known to affect immune function. The tuberculin test was performed 8 weeks after vaccination and tuberculin response and hormone levels were compared between prepubertal and pubertal subjects. We found a higher tuberculin response in the pubertal group when compared with the prepubertal ones. The pubertal children had 79.1 per cent tuberculin positivity compared with 46.4 per cent of prepubertal children (p < 0.05). Diameters of induration of the tuberculin test among prepubertal students vs. pubertal students were 9.5 +/- 3.8 mm and 11.9 +/- 3.7 mm, respectively (p < 0.005). Pubertal stage, testis volume, and pubic stage were also found to have significant effects on tuberculin test results. No difference was observed between both sexes with regard to responses of the tuberculin test in either the prepubertal or the pubertal group (p > 0.05). DHEAS and AED levels in the tuberculin-positive subjects were found to be significantly higher than tuberculin-negative ones (p = 0.040 and p = 0.046, respectively). Among both these hormones, only AED levels were correlated with tuberculin test responses. These results suggest that AED may play a role in the immunity to BCG vaccination and further immunological investigations are warranted to provide support for this idea.

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., (Copyright Society for Adolescent Medicine, 2003)

Immunity to Plasmodium falciparum develops slowly in areas of endemicity, and this is often ascribed to poorly immunogenic or highly variant parasite antigens. However, among populations newly exposed to malaria, adults acquire immunity more rapidly than children. We examined the relationship between pubertal development and resistance to P. falciparum. During two transmission seasons in western Kenya, we treated the same cohort of young males to eradicate P. falciparum and then obtained blood smears each week for 4 months. We determined pubertal development by Tanner staging and by levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone in plasma. In multivariate and age-stratified analyses, we examined the effect of pubertal development on resistance to malaria. In both seasons (n = 248 and 144 volunteers, respectively), older males were less susceptible than younger males. Age-related decreases in the frequency and density of parasitemia were greatest during puberty (15- to 20-year-olds). DHEAS and testosterone were significant independent predictors of resistance to P. falciparum parasitemia, even after accounting for the effect of age. Fifteen- to 20-year-old males with high DHEAS levels had a 72% lower mean parasite density (P<0.01) than individuals with low DHEAS levels. Similarly, 21- to 35-year-old males with high DHEAS levels had a 92% lower mean parasite density (P<0.001) and 48% lower frequency of parasitemia (P<0.05) than individuals with low DHEAS levels. These data suggest that the long period needed to attain full immunity could be explained as a consequence of host development rather than as the requirement to recognize variant or poorly immunogenic parasite antigens.

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.

Problem: Antisperm antibodies induced in prepubertal boys with testicular failures were characterized by using four techniques of antibody detection. The reactivity of circulating antisperm antibodies in prepubertal boys and the reactivity of antibodies in sera samples of adult fertile and infertile males were compared against the same sperm antigenic pools (live or fixed spermatozoa, or sperm antigenic extracts)., Method of Study: The incidence of antisperm antibodies in sera samples of 69 prepubertal boys with testicular failures and 21 samples obtained from adult, male individuals was assessed by indirect immunobead binding test (IDIBT), flow cytometry measurement, enzyme-linked immunosorbent assay, and Western blotting. Immunoblot analysis was performed by using sperm extracts of glycosylated and deglycosylated solubilized membrane antigens., Results: Sera samples were studied in a group composed of healthy prepubertal boys (n = 7) and prepubertal boys with testicular failures (n = 69). Applied tests of antibody detection revealed striking differences in a group of boys with testicular pathology. With IDIBT, 7% of the sera samples were found positive, whereas with flow cytometry measurement, 48% of the sera samples were positive. Immunosorbent assay (fixed sperm) indicated 32% positive cases in the same group. The sera samples were found to be positive in 65% of immunoblotting reactions with glycosylated antigens and in 70% of immunoblotting reactions with deglycosylated antigens. All applied detection assays were clearly negative on sera samples from fertile, adult males. Western immunoblotting indicated an immunodominant antigenic determinant of 58 kDa., Conclusions: Tests of antibody detection with the use of live sperm (IDIBT and flow cytometry measurements) presented low sensitivity (8% and 48%, respectively) in a group of prepubertal boys. This observation underlines the difficulties in assigning the prospective prognosis of future fertility status in prepubertal boys with antisperm antibodies.

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.

Objectives: To determine the immunologic response to a brief bout of intense exercise in children and to determine the effects of prolonged activity and maturation level of the subjects on this response., Study Design: We determined counts of leukocytes and their subsets, counts of lymphocytes and their subsets, and natural killer (NK) cell activity and cell number before and 3 and 60 minutes after a Wingate anaerobic test (WAnT) in 16 male swimmers (9 to 17 years of age) and 17 male nonswimmers (9 to 17 years of age). Subjects were also categorized by pubertal status based on Tanner staging and by level of physical activity. The Student t test and analysis of variance were used to determine statistical significance, with values expressed as mean +/- SEM., Results: Three minutes after the WAnT, all children had increases in leukocytes (28%), lymphocytes (43%), and NK cells (395%) (p < 0.01). Swimmers had less baseline NK cell activity (54 +/- 6 cytolytic units) than nonswimmers (87 +/- 10 cytolytic units) after the WAnT (p < 0.01), although both groups showed an increase to similar levels of NK activity 3 minutes after exercise. Pubertal effects on these responses were not significant., Conclusions: Our results demonstrate transient leukocytosis, lymphocytosis, and increases in NK cell number and activity in 8- to 17-year-old boys after a brief bout of intense exercise. Formal athletic training appears to be associated with a lower baseline NK cell activity, and yet such activity is still within the normal range for this age group. Further investigations are necessary to determine the impact of such training on overall health and the ability to fight infection.

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.

We studied the effect of pubertal development on insulin secretion. Intravenous glucose tolerance tests were performed on 47 islet-cell antibody negative siblings of diabetic children and on 16 normal adults. Puberty was staged using Tanner's criteria and subjects were grouped as follows: I, stage 1 (n = 16); II, stages 2 and 3 (n = 15); III, stages 4 and 5 (n = 16); IV, adults (n = 16). Fasting insulin increased with advancing puberty (p = 0.59, P less than 0.001). The stimulated insulin response also rose with increasing pubertal development: for the 0-10 min insulin area, p = 0.46, P less than 0.001 and for the 10-60 min area, p = 0.68, P less than 0.001. There was a low positive correlation between insulin and age to 16 years but multiple regression analysis showed that this could be accounted for by puberty alone. Indeed prepubertal children and adults did not differ. There was no correlation between glucose (fasting and 0-60 min area) and puberty or age. These findings suggest that insulin resistance increases during puberty, and this may contribute to the frequency of presentation or worsening control of insulin dependent diabetes at this time.