Conception and pilot testing of a self-management health application for patients with pollen-related allergic rhinitis and allergic asthma-the APOLLO app.

It has been shown that pollen information services are an important self-management tool for patients with pollen-related allergic rhinitis (AR) and allergic asthma (AA). This study aimed to design an online application for patients with AR and AA, which supports patients to better manage their disease as well as to evaluate the app and present the first results of the pilot study. The pollen data were obtained from the electronic pollen information network of Bavaria, Germany. Participants were asked to fill in their allergy-related complaints in the app over a 60-day period. Subsequently, the app was evaluated. Indices and diagrams visualized the participants' individual complaints as well as the daily pollen concentration in the air. In order to motivate participants to complete the app on a daily basis, we used elements of gamification. Two thirds of the participants (N = 46) reported feeling better informed about pollen counts and their allergy when using the app. The app's simple and comprehensible design was rated positively. More than 80% of the participants would recommend the app to their family and friends. The app can be a tool for patients with AR and AA to better understand their disease.

Increased breath naphthalene in children with asthma and wheeze of the All Age Asthma Cohort (ALLIANCE).

Exhaled breath contains numerous volatile organic compounds (VOCs) known to be related to lung disease like asthma. Its collection is non-invasive, simple to perform and therefore an attractive method for the use even in young children. We analysed breath in children of the multicenter All Age Asthma Cohort (ALLIANCE) to evaluate if 'breathomics' have the potential to phenotype patients with asthma and wheeze, and to identify extrinsic risk factors for underlying disease mechanisms. A breath sample was collected from 142 children (asthma: 51, pre-school wheezers: 55, healthy controls: 36) and analysed using gas chromatography-mass spectrometry (GC/MS). Children were diagnosed according to Global Initiative for Asthma guidelines and comprehensively examined each year over up to seven years. Forty children repeated the breath collection after 24 or 48 months. Most breath VOCs differing between groups reflect the exposome of the children. We observed lower levels of lifestyle-related VOCs and higher levels of the environmental pollutants, especially naphthalene, in children with asthma or wheeze. Naphthalene was also higher in symptomatic patients and in wheezers with recent inhaled corticosteroid use. No relationships with lung function or TH2 inflammation were detected. Increased levels of naphthalene in asthmatics and wheezers and the relationship to disease severity could indicate a role of environmental or indoor air pollution for the development or progress of asthma. Breath VOCs might help to elucidate the role of the exposome for the development of asthma. The study was registered at ClinicalTrials.gov (NCT02496468).

Cytokine levels in children and adults with wheezing and asthma show specific patterns of variability over time.

Levels of cytokines are used for in-depth characterization of patients with asthma; however, the variability over time might be a critical confounder. To analyze the course of serum cytokines in children, adolescents and adults with asthma and in healthy controls and to propose statistical methods to control for seasonal effects. Of 532 screened subjects, 514 (91·5%) were included in the All Age Asthma Cohort (ALLIANCE). The cohort included 279 children with either recurrent wheezing bronchitis (more than two episodes) or doctor-diagnosed asthma, 75 healthy controls, 150 adult asthmatics and 31 adult healthy controls. Blood samples were collected and 25 µl serum was used for analysis with the Bio-Plex Pr human cytokine 27-Plex assay. Mean age, body mass index and gender in the three groups of wheezers, asthmatic children and adult asthmatics were comparable to healthy controls. Wheezers (34·5%), asthmatic children (78·7%) and adult asthmatics (62·8%) were significantly more often sensitized compared to controls (4·5, 22 and 22·6%, respectively). Considering the entire cohort, interleukin (IL)-1ra, IL-4, IL-9, IL-17, macrophage inflammatory protein (MIP)-1- α and tumor necrosis factor (TNF)- α showed seasonal variability, whereas IL-1ß, IL-7, IL-8, IL-13, eotaxin, granulocyte colony-stimulating factor (G-CSF), interferon gamma-induced protein (IP)-10, MIP-1 ß and platelet-derived growth factor (PDGF)-BB did not. Significant differences between wheezers/asthmatics and healthy controls were observed for IL-17 and PDGF-BB, which remained stable after adjustment for the seasonality of IL-17. Seasonality has a significant impact on serum cytokine levels in patients with asthma. Because endotyping has achieved clinical importance to guide individualized patient-tailored therapy, it is important to account for seasonal effects.

Congenital syphilis: A prospective study of 22 cases diagnosed by PCR.

Congenital syphilis (CS) is caused by Treponema pallidum infection in utero. There is a need to develop new tools to diagnose CS: the diagnostic value of PCR is difficult to assess. The aim of this study was to describe the clinical and laboratory characteristics of mothers and infants with CS as diagnosed by PCR tests on various maternal and neonatal samples. PATIENTS AND METHODS: We included all infants epidemiologically linked to a mother diagnosed with syphilis whose samples were referred to the Syphilis Reference Center, and for whom at least one positive PCR result was obtained. RESULTS: Twenty-two mother-infant pairs (8.3%) with assay performed on samples from one to four different anatomic sites were included between February 2011 and April 2018. Seven mothers (31.8%) were born abroad, fifteen (68.2%) presented psychological and/or social problems, eight (36.4%) had not been screened for syphilis prior to delivery, and eleven (50%) were referred from French overseas departments or territories, or from the Paris region. Six infants (27.3%) were stillborn and six were born preterm, while fifteen infants (68.2%) presented clinical features of CS. All infants born preterm were symptomatic. Infant VDRL/RPR titer was no greater than four times that in the mother's serum, except in two cases. DISCUSSION: Lack of antenatal care, social disadvantage and psychological issues were common. There is a need for enhanced surveillance both in the French overseas departments/territories and in the Paris region. A larger study is required to assess the sensitivity and specificity of PCR. The best site for sampling has yet to be established. We recommend the collection of as many samples as possible to avoid underdiagnosis of CS.

Early age exposure to moisture damage and systemic inflammation at the age of 6 years.

Cross-sectional studies have shown that exposure to indoor moisture damage and mold may be associated with subclinical inflammation. Our aim was to determine whether early age exposure to moisture damage or mold is prospectively associated with subclinical systemic inflammation or with immune responsiveness in later childhood. Home inspections were performed in children's homes in the first year of life. At age 6 years, subclinical systemic inflammation was measured by serum C-reactive protein (CRP) and blood leukocytes and immune responsiveness by ex vivo production of interleukin 1-beta (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α) in whole blood cultures without stimulation or after 24 hours stimulation with phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG) in 251-270 children. Moisture damage in child's main living areas in infancy was not significantly associated with elevated levels of CRP or leukocytes at 6 years. In contrast, there was some suggestion for an effect on immune responsiveness, as moisture damage with visible mold was positively associated with LPS-stimulated production of TNF-α and minor moisture damage was inversely associated with PI-stimulated IL-1ß. While early life exposure to mold damage may have some influence on later immune responsiveness, it does not seem to increase subclinical systemic inflammation in later life.

A switch in regulatory T cells through farm exposure during immune maturation in childhood.

BACKGROUND: Farm exposure protects against development of allergies early in life. At 4.5 years, protection against asthma by farm-milk exposure was partially mediated by regulatory T cells (Tregs). The aim of this study was to investigate the critical time window of the 'asthma-protective' farm effect via Tregs during childhood immune maturation. METHODS: Tregs were assessed longitudinally at 4.5 and 6 years in 111 children (56 farm and 55 reference children) from the PASTURE/EFRAIM birth cohort (flow cytometry). Peripheral blood mononuclear cells were cultured unstimulated (U), with phorbol 12-myristate 13-acetate/ionomycin (PI) or lipopolysaccharide (LPS), and stained for Tregs (CD4+ CD25high FOXP3upper20% ). mRNA expression of Treg/Th1/Th2/Th17-associated cell markers was measured ex vivo. Suppressive capacity of Tregs on effector cells and cytokines was assessed. Detailed questionnaires assessing farm exposures and clinical phenotypes from birth until age 6 years were answered by the parents. RESULTS: Treg percentage before and after stimulation and FOXP3mRNA expression ex vivo decreased from age 4.5 to 6 years (P(U,LPS) < 0.001; P(PI) = 0.051; P(FOXP3) < 0.001). High vs low farm-milk and animal-stable exposure was associated with decreased LPS-stimulated Treg percentage at age 6 years (P(LPS) = 0.045). Elevated LPS-stimulated-Treg percentage at age 6 was associated with increased risk of asthma (aOR = 11.29, CI: 0.96-132.28, P = 0.053). Tregs from asthmatics vs nonasthmatics suppressed IFN-γ (P = 0.015) and IL-9 (P = 0.023) less efficiently. mRNA expression of Th1/Th2/Th17-associated cell markers decreased between 4.5 and 6 years (P < 0.001). CONCLUSIONS: Tregs at the age of 6 years were decreased with farm exposure and increased within asthmatics, opposite to age 4.5 years. This immunological switch defines a critical 'time window' for Treg-mediated asthma protection via environmental exposure before age 6 years.

[Assessment of screening for Down syndrome in Martinique from 2011 to 2013: An island location favoured]. / Évaluation du dépistage de la trisomie 21 en Martinique de 2011 à 2013 : une situation insulaire privilégiée.

OBJECTIVES: The aim of this study is to evaluate the screening for trisomy 21 (T21) between 2011 and 2013 on Martinique French West Indies after the decree of 23 June 2009. MATERIALS AND METHODS: Were used the prenatal data provided by accredited laboratories and the data from the Registry of Congenital French West Indies (REMALAN). RESULTS: A total of 85.9 % of patients underwent screening: 60.5 % on a combined calculation of risk (CRC), 14.6 % on a sequential calculation of risk (CRS) and 10.8 % on serum markers 2nd trimester (MST2). Overall 5.4 % of the patients were placed in a risk group. During this period, 47 trisomy 21 were identified by the REMALAN which 38 (80.1 %) were detected prenatally: 24 of CRC, 3 on MST2 and 11 on signs of ultrasound at the 1st and 2nd trimester. The sensitivity of the CRC was 88 % for a false positive rate of 3.87 %. The overall sensitivity of screening (CRC, CRS and MST2) was 87 % for a false positive rate of 5.21 %. CONCLUSION: These data show that the coverage rate in Martinique is satisfactory and the screening fir Down syndrome meet expectations.

Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age.

Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.

Exposure to a farm environment is associated with T helper 1 and regulatory cytokines at age 4.5 years.

BACKGROUND: Farm exposure has been shown to protect from childhood asthma and allergic diseases, but underlying immunological mechanisms are not clear yet. OBJECTIVE: To explore whether farming lifestyle determines cytokine profile of peripheral blood mononuclear cells (PBMCs) of 4.5-year-old children (n = 88) from the Finnish PASTURE birth cohort study. METHODS: We analysed regulatory (IL-10, IL-2), T helper 1 (Th1)-associated (IL-12, IFN-γ), inflammatory (IL-1ß, TNF, CXCL8) and Th2-associated (IL-13) cytokines in unstimulated PBMCs and after a short-term (5 h) stimulation with lipopolysaccharide (LPS). Specific farm exposures (stables, hay barn, farm milk) at age 4 years were assessed from questionnaires. RESULTS: The unstimulated PBMCs of farm children produced more IL-10 (GMR 1.22, P = 0.032), IL-12 (GMR 1.24, P = 0.012) and IFN-γ (GMR 1.24, P = 0.024) than those of non-farm children. Also, specific farm exposures were associated with higher spontaneous production of cytokines. The number of specific farm exposures tended to be dose dependently associated with higher spontaneous production of IFN-γ (test for trends, P = 0.013) and lower LPS-induced production of TNF (test for trends, P = 0.025). CONCLUSION AND CLINICAL RELEVANCE: Farming lifestyle seemed to be associated with increased spontaneous production of Th1 and regulatory cytokines. Decreased TNF responses to short-term LPS stimulation in farm-exposed children may imply tolerogenic immune mechanisms. These novel findings might contribute to the asthma and allergy protection in farm environment.

Moisture damage in home associates with systemic inflammation in children.

This study investigated the association between confirmed moisture damage in homes and systemic subclinical inflammation in children. Home inspections were performed in homes of 291 children at the age of 6 years. Subclinical inflammation at the age of 6 years was assessed by measuring the circulating levels of C-reactive protein (CRP) and leukocytes in peripheral blood and fractional exhaled nitric oxide (FeNO). Proinflammatory cytokines interleukin (IL)-1ß and IL-6 and tumor necrosis factor (TNF)-α were measured in unstimulated, and in phorbol 12-myristate 13-acetate and ionomycin (PI), lipopolysaccharide (LPS), or peptidoglycan (PPG)-stimulated whole blood. Major moisture damage in the child's main living areas (living room, kitchen, or child's bedroom) and moisture damage with mold in the bathroom were associated with increased levels of CRP and stimulated production of several proinflammatory cytokines. There were no significant associations between moisture damage/visible mold and leukocyte or FeNO values. The results suggest that moisture damage or mold in home may be associated with increased systemic subclinical inflammation and proinflammatory cytokine responsiveness.

Farm exposures are associated with lower percentage of circulating myeloid dendritic cell subtype 2 at age 6.

BACKGROUND: Early life farm exposures have been shown to decrease the risk of allergic diseases. Dendritic cells (DCs) may mediate asthma-protective effect of farm exposures as they play an important role in the development of immunity and tolerance. Our aim was to investigate whether the numbers and phenotypes of circulating DCs at age 6 are associated with farming, asthma, and atopy in a selected sample of French and Finnish children from the PASTURE study. METHODS: We studied 82 farm and 86 nonfarm children with and without asthma. Using flow cytometry, BDCA1+ CD11c+ myeloid DC1s (mDC1), BDCA3+(high) mDC2s and BDCA2+ plasmacytoid DCs (pDCs) were identified and expressions of CD86, immunoglobulin-like transcript 3 (ILT3) and ILT4 were analyzed. Questionnaires were used to assess prenatal and lifetime patterns of farm exposures and to define asthma. Atopic sensitization was defined by specific IgE measurements. RESULTS: The percentage of mDC2 cells was lower in farm children (0.033 ± 0.001) than in nonfarm children (0.042 ± 0.001; P = 0.008). Similar associations were found between mDC2 percentage and prenatal (P = 0.02) and lifetime exposure to farm milk (P = 0.03) and stables (P = 0.003), but these associations were not independent from farming. Asthma was positively associated with ILT4 + mDCs (P = 0.04) and negatively with CD86 + pDCs (P = 0.048) but only in nonfarm children. CONCLUSIONS: Inverse association between farm exposure and mDC2 percentage suggest that this DC subset may play a role in farm-related immunoregulation.

IL-37 requires IL-18Rα and SIGIRR/IL-1R8 to diminish allergic airway inflammation in mice.

BACKGROUND: Interleukin (IL) 37 has been described as a negative regulator of innate immunity, as it reduces the activation and cytokine production of different innate immune cells. Recently, results from the CLARA childhood asthma cohort suggested an implication of IL-37 for human asthma pathogenesis. This study aimed to investigate the effects of IL-37 on allergic airway inflammation in a mouse model of experimental asthma. METHODS: Peripheral blood mononuclear cells (PBMCs) of children were cultured for 48 h (anti-CD3/anti-CD28 stimulation or unstimulated), and IL-37 concentrations in supernatants were determined. Wild-type, IL-18Rα-deficient ((-/-) ), and SIGIRR(-/-) C57BL/6 mice were sensitized to ovalbumin (OVA) and challenged with OVA aerosol to induce acute experimental asthma, and IL-37 was applied intranasally prior to each OVA challenge. Airway hyper-responsiveness (AHR), airway inflammation, cytokine levels in broncho-alveolar lavage fluid, and mucus production were determined. RESULTS: IL-37 production of human PBMCs was significantly lower in allergic asthmatics vs healthy children. In wild-type mice, intranasal administration of IL-37 ablated allergic airway inflammation as well as cytokine production and subsequently diminished the hallmarks of experimental asthma including mucus hyperproduction and AHR. In contrast, local application of IL-37 produced none of these effects in mice lacking either IL18Rα or SIGIRR/IL-1R8. CONCLUSIONS: This study demonstrates that IL-37 is able to ablate a TH2 cell-directed allergic inflammatory response and the hallmarks of experimental asthma in mice, suggesting that IL-37 may be critical for asthma pathogenesis. Furthermore, these data suggest a mode of action of IL-37 that involves IL18Rα as well as the orphan receptor SIGIRR/IL-1R8.

Atopic dermatitis, STAT3- and DOCK8-hyper-IgE syndromes differ in IgE-based sensitization pattern.

BACKGROUND: Increased serum IgE levels are characteristic but not specific for allergic diseases. Particularly, severe atopic dermatitis (AD) overlaps with hyper-IgE syndromes (HIES) regarding eczema, eosinophilia, and increased serum IgE levels. HIES are primary immunodeficiencies due to monogenetic defects such as in the genes DOCK8 and STAT3. As it is not known to date why allergic manifestations are not present in all HIES entities, we assessed the specificity of serum IgE of AD and HIES patients in the context of clinical and immunological findings. METHODS: Clinical data, skin prick tests, specific IgE to aero- and food allergens, and T helper (Th) subpopulations were compared in AD and molecularly defined HIES patients. RESULTS: Total serum IgE levels were similarly increased in STAT3-HIES, DOCK8-HIES, and AD patients. The ratio of aeroallergen-specific IgE to total IgE was highest in AD, whereas DOCK8-HIES patients showed the highest specific serum IgE against food allergens. Overall, clinical allergy and skin prick test results complied with the specific IgE results. Th2-cell numbers were significantly increased in DOCK8-HIES and AD patients compared to STAT3-HIES patients and controls. AD patients showed significantly higher nTreg-cell counts compared to STAT3-HIES and control individuals. High Th17-cell counts were associated with asthma. Specific IgE values, skin prick test, and T-cell subsets of STAT3-HIES patients were comparable with those of healthy individuals except decreased Th17-cell counts. CONCLUSION: Hyper-IgE syndromes and atopic dermatitis patients showed different sensitization pattern of serum IgE corresponding to the allergic disease manifestations and Th-cell subset data, suggesting a key role of DOCK8 in the development of food allergy.

STAT6 polymorphisms are associated with neonatal regulatory T cells and cytokines and atopic diseases at 3 years.

BACKGROUND: The transcription factor STAT6 is crucial for activation of the interleukin (IL)-4/IL-13 pathway and has been linked to regulatory T cells (Tregs). Associations of STAT6 polymorphisms with IgE levels were described; however, their impact on neonatal immune responses and early disease development is unknown. METHODS: STAT6 polymorphisms were genotyped in cord blood mononuclear cells by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Gene expression was assessed by real-time polymerase chain reaction (PCR) and cytokines by Multiplex. At age 3 years, atopic diseases were assessed by questionnaires. RESULTS: STAT6 rs324011 but not rs1059513 polymorphism was associated with significant or borderline significant decreased mRNA expression of Treg-associated genes (FOXP3, GITR, LAG3). Heterozygotes and minor allele homozygotes of rs324011 had low levels of tumor necrosis factor alpha (TNF-α) and increased interferon gamma (IFN-γ) (P ≤ 0.04), while heterozygotes and minor allele homozygotes of rs1059513 had increased TNF-α and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (P ≤ 0.05). In minor allele homozygotes of rs324011, expression of Treg-associated genes was strongly inverse correlated with IFN-γ (unstimulated, r = -0.7, P = 0.111; LpA stimulation, r = -0.8, P = 0.011), but not in heterozygotes or major allele homozygotes. Heterozygotes and minor allele homozygotes of rs324011 presented a lower risk of atopic dermatitis and obstructive bronchitis until age 3 years. CONCLUSIONS: Two STAT6 polymorphisms were associated with altered immune responses already at birth. STAT6 rs324011 was associated with lower neonatal Treg and increased Th1 response. Those neonates had a lower risk of atopic dermatitis and obstructive bronchitis until 3 years. Our data suggest a role for STAT6 polymorphisms in early immune regulation and implications on early atopic disease development.

TLR2 polymorphisms influence neonatal regulatory T cells depending on maternal atopy.

BACKGROUND: Toll-like receptor (TLR) polymorphisms have been associated with atopic diseases in children and adults. Development of atopic diseases may be modified by TLR-mediated signals that modulate T-regulatory cells (Tregs) early in life when maternal influences are still present and relevant. The aim of this study was to assess whether genetic TLR variants influence Tregs in neonates. METHODS: Twelve single nucleotide polymorphisms located in TLR1, TLR2, TLR4, TLR6, and TLR10 were genotyped in 200 cord blood samples (72 samples from atopic, 128 from nonatopic mothers). Cord blood mononuclear cells were cultured without or with stimulation [lipid A (LpA), peptidoglycan (Ppg), phytohemagglutinin, house dust mite]. mRNA expression of Treg marker genes [forkhead box protein P3 (FOXP3), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte activation gene 3 (LAG3)], TLR2, Th1/Th2 cytokines, and tumor necrosis factor alpha (TNF-α) was measured. RESULTS: In children with the AA genotype of the TLR2 promoter variant rs4696480, gene expression of FOXP3 and Treg marker genes GITR and LAG3 as well as Th2 cytokines and TNF-α secretion was significantly increased in the presence of maternal atopy and Tregs decreased without maternal atopy. In carriers of the GG genotype for TLR2 rs1898830, gene expression of Treg marker genes was significantly decreased with and increased without maternal atopy. FOXP3 expression was also modified by TLR1 rs4833095 (P ≤ 0.03) and trendwise by TLR10 rs4129009 after LpA and Ppg stimulation. CONCLUSIONS: Genetic variations of TLR2, TLR1, and TLR10 affect Treg marker gene expression in cord blood. Gene-immunological interactions of the TLR pathway influence Tregs early in life, modulated by maternal atopy. This may be relevant for immune maturation in the development of atopic diseases in childhood.

Impairment of T helper and T regulatory cell responses at birth.

BACKGROUND: There is strong evidence that reduced exposures to microbial compounds triggering innate immune responses early in life are critical for the development of allergic illnesses. The underlying mechanisms remain unknown, but will include T-cell responses either along T helper type 1 (Th1)/Th2 pathways or via T regulatory and Th17 cells. Yet, little is known about innate immune responses and the function of T regulatory/Th17 cells at birth. The aim of this study was to investigate T-cell responses to innate (Lipid A/LpA, peptidoglycan/Ppg) and adaptive (phytohemagglutinin) stimuli at birth and to compare these findings with adult immune responses. METHODS: Cord and peripheral blood mononuclear cells including T regulatory and Th17 cells from 25 neonates and 25 adults were examined for proliferation, cytokine secretion, surface, mRNA expression and functional suppression assays. RESULTS: Proliferation and cytokine responses to innate stimuli were less mature at birth than in adulthood. T regulatory and Th17 cells were less expressed in cord than in adult blood (Ppg-induced Foxp3, P = 0.001, LpA-induced CD4(+) CD25(+) high, P = 0.02; Th17 : P < 0.0001). Mitogen-induced suppression of T-regulatory cells on T-effector cell function was less efficient in cord than in adult blood (P = 0.01). At both ages, Th17 cells were correlated with Th1/Th2 cells (P < 0.01), but not with interleukin-10 secretion following innate-stimulation. CONCLUSION: Innate immune responses are immature at birth. Furthermore, the function of T regulatory and Th17 cells is impaired. Th17 cells in association with Th1/Th2 cells may be involved in early immuno-modulation. Potent innate immune stimulation early in life can potentially contribute to protection from allergic diseases.

Dissection of a novel molecular determinant mediating Golgi to trans-Golgi network transition.

Two major functions of the Golgi apparatus (GA) are formation of complex glycans and sorting of proteins destined for various subcellular compartments or secretion. To fulfill these tasks proper localization of the accessory proteins within the different sub-compartments of the GA is crucial. Here we investigate structural determinants mediating transition of the two glycosyltransferases beta-1,4- galactosyltransferase 1 (gal-T1) and the alpha-1,3-fucosyltransferase 6 (fuc-T6) from the trans-Golgi cisterna to the trans-Golgi network (TGN). Upon treatment with the ionophore monensin both glycosyltransferases are found in TGN-derived swollen vesicles, as determined by confocal fluorescence microscopy and density gradient fractionation. Both enzymes carry a signal consisting of the amino acids E(5)P(6) in gal-T1 and D(2)P(3) in fuc-T6 necessary for the transition of these glycosyltransferases from the trans-Golgi cisterna to the TGN, but not for their steady state localization in the trans-Golgi cisterna.

Fetal cord blood: aspects of heightened immune responses.

Neonatal immune responses have been associated with the development of atopy in childhood. We assessed in cord blood mononuclear cells (CBMC) whether increased allergen/mitogen-induced lymphoproliferation (LP) is associated with pro-allergic Th2 cytokine IL-13 or Th1 cytokine IFN-gamma secretion. We determined whether LP to one allergen is related to heightened lymphocyte function to other allergens/mitogen. CBMC from 135 neonates were stimulated with house dust mite (Derf1), cockroach, ovalbumin, or mitogen. LP to one allergen was associated with significantly increased LP to other allergens/mitogen. Increased Derf1-LP was associated with increased Derf1-induced IL-13 secretion (r = 0.21, p = 0.01). After adjusting for neonatal gender, race, and maternal smoking, Derf1-LP remained associated with Derf1-IL-13 (OR 3.08, 95% CI 1.56-6.10). Increased mitogen-induced proliferation was associated with increased mitogen-induced IL-13 secretion (r = 0.37, p < 0.001). For some individuals, a predisposition to a heightened immune response is already evident at birth. Whether this phenotype results in atopy in childhood warrants further investigation.