Effect of weekly vitamin D supplementation on the severity of atopic dermatitis and type 2 immunity biomarkers in children: A randomized controlled trial.

BACKGROUND: Vitamin D (VD) deficiency is common among patients with atopic dermatitis (AD) and often associated with severity. However, randomized trials of VD supplementation in AD have had equivocal results, and there is little information regarding the effect of VD supplementation on type 2 immunity in AD patients. OBJECTIVES: To investigate the efficacy of VD supplementation to decrease severity of AD and to alter type 2 immunity biomarkers. METHODS: We performed a randomized, double-blind, placebo-controlled trial. We randomly assigned 101 children with AD to weekly oral vitamin D3 (VD3) or placebo for 6 weeks. The primary outcome was the change in the Severity Scoring of AD (SCORAD). RESULTS: Mean age of subjects was 6.3 ± 4.0 years, and baseline SCORAD was 32 ± 29. At baseline, 57% of children were VD deficient, with no difference between groups. Change in 25(OH)D was significantly greater with VD3 than placebo (+43.4 ± 34.5 nmol/L vs. +2.3 ± 21.2 nmol/L, p < 0.001). SCORAD change at 6 weeks was not different between VD and placebo (-5.3 ± 11.6 vs. -5.5 ± 9.9, p = 0.91). There were no significant between-group differences in change of eosinophil counts, total IgE, Staphylococcal enterotoxin specific IgE, CCL17, CCL22, CCL27, LL-37 or Staphylococcus aureus lesional skin colonization. Vitamin D receptor (VDR) gene single nucleotide polymorphisms FokI, ApaI and TaqI did not modify subjects' response to VD supplementation. CONCLUSIONS: Among children with AD, weekly VD supplementation improved VD status but did not modify AD severity or type 2 immunity biomarkers compared to placebo (ClinicalTrials.gov NCT01996423).

High prevalence of lupin allergy among patients with peanut allergy: Identification of γ-conglutin as major allergen.

BACKGROUND: Lupin is a protein-rich legume with a growing presence in the food market worldwide. With increased consumption, lupin allergy (LA) reports are also rising. Uncertainties exist on the cross-reactivity between peanut and lupin, the allergenic potential of different lupin species, and sensitization patterns among different populations. OBJECTIVE: To evaluate the molecular basis of LA and to determine lupin allergens from 3 different species that may be involved in peanut allergy (PA) cross-reactivity. METHODS: A total of 43 subjects with PA, those with LA, or controls without food allergy were evaluated with skin prick tests (SPTs) and specific IgEs (sIgEs). Lupin-sensitized subjects were offered a lupin oral food challenge (OFC). Immunoblots and enzyme-linked immunosorbent assays were performed on sera from lupin-sensitized subjects. RESULTS: In this study, 44% of the PA subjects were confirmed to have LA by OFC. Anaphylaxis was the most frequent manifestation after lupin consumption, with a minimal eliciting dosage of 1 g lupin flour. There was no difference in lupin sIgE or SPT wheal size between lupin-sensitized and confirmed LA subjects or in the severity of symptoms among confirmed LA subjects. Sera from lupin-sensitized subjects uniformly reacted to all 3 different lupin species. Immunoblotting and enzyme-linked immunosorbent assays revealed immunoglobulin E binding to α- and γ-conglutin in all analyzed sera, whereas α- and ß-conglutin recognition was variable. CONCLUSION: Our findings reveal a high prevalence of LA among PA subjects, emphasizing lupin must be labeled as an allergen in foods. Owing to high variability in lupin-sIgE and lupin-SPT results, LA diagnosis may require OFC. In our population, γ-conglutin is the major allergen of lupin.

Association between obesity and atopic dermatitis in children: A case-control study in a high obesity prevalence population.

BACKGROUND/OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Research suggests an association between obesity and AD, although evidence is lacking from Latin American populations. This study evaluated the association of obesity with AD in children from Chile, a country with high obesity prevalence. METHODS: A case-control study was performed in children with active AD (cases) and healthy controls (HCs) from Santiago, Chile. Body mass index was evaluated by z-score (z-BMI), with overweight defined as z-BMI ≥+1 and <+2, and obesity as z-BMI ≥+2. Abdominal obesity was defined by a waist circumference-to-height ratio (WHR) ≥0.5. AD severity was evaluated by Scoring AD (SCORAD) index. RESULTS: A total of 174 children with AD and 101 controls were included. AD patients had similar overweight (27% vs. 28%) and obesity (21% vs. 26%) rates as HCs (p = .65). Abdominal obesity rates were also comparable (64% vs. 62%, p = .81). In sex-specific analyses, girls with AD had higher abdominal obesity rates than HCs (71% vs. 53%, p < .05) while boys with AD had lower abdominal obesity rates than HCs (53% vs. 75%, p = .03). Among children with AD, higher z-BMI or WHR did not correlate with higher SCORAD, eosinophil counts or total IgE. CONCLUSION: In our study, Chilean children with AD had high but similar rates of obesity as HCs, but showed sex-specific associations of abdominal obesity and AD. Further research is needed to evaluate these associations and the roles that weight excess and weight loss could play in the pathogenesis and treatment of AD.

A cluster randomized trial of interferon ß-1a for the reduction of transmission of SARS-Cov-2: protocol for the Containing Coronavirus Disease 19 trial (ConCorD-19).

BACKGROUND: SARS-CoV-2 infection rapidly spreads in populations due to the high rates of community transmission. Interrupting the shedding of SARS-CoV-2 may reduce the incidence of Coronavirus Disease 19 (COVID-19). Herein we provide a protocol for a cluster randomized trial that will examine the effectiveness of treatment with interferon (IFN) ß-1a compared to standard of care in limiting the transmission of SARS-CoV-2. Co-primary objectives are to determine whether IFN therapy reduces (a) the proportion of infected cases shedding SARS-CoV-2 at day 11 post randomization and (b) the incidence of transmission of SARS-CoV-2 infection from index cases to treatment-eligible household post-exposure contacts at day 11 after randomization. Secondary objectives include assessing the impact of IFN treatment on duration of viral clearance, hospitalizations and fatalities, and evaluating the safety of IFN treatment. METHODS: Three hundred and ten households, each including an index case with a recent COVID-19 diagnosis and at least one asymptomatic treatment-eligible household contact, will be randomized to receive 3 doses of 125 µg IFN ß-1a by subcutaneous administration (days 1, 6, and 11), or standard of care. All participants will be followed until day 29. DISCUSSION: The results from this trial will identify whether IFN ß treatment of mild or moderate COVID-19 cases accelerates viral clearance and prevents disease progression and whether IFN ß treatment of post-exposure contacts of COVID-19 cases reduces transmission of infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov NCT04552379; date of registration September 17, 2020.

Early origins of allergy and asthma (ARIES): study protocol for a prospective prenatal birth cohort in Chile.

BACKGROUND: Growing evidence shows that atopic dermatitis (AD), food allergy (FA), allergic rhinitis, and asthma are largely determined during the first 1000 days (time elapsed from conception to the 2nd birthday). The ARIES birth cohort aims to determine prenatal and perinatal conditions, as well as genetic and epigenetic factors, that participate in the early setting of immune responses, and the role of these in the later determination of the risk of allergic diseases and asthma in the offspring. METHODS: We have designed a birth cohort of 250 families with prenatal recruitment (~ 14 weeks). We will genotype relevant allergy/asthma-associated variants in trios and will perform immunophenotyping and evaluation of allergy biomarkers in cord blood. At 1 and 2 years of age we will assess if infants have developed allergic sensitization, AD, FA, as well as biomarkers of asthma including the asthma predictive index. We will also evaluate how maternal conditions modify immune programming through epigenetic modifications and will then depict newborn epigenetic cues of allergy/asthma risk. Next, we will assess composition/diversity of maternal gut, placenta, breastmilk and infant gut microbiome and their association with immunophenotype and biomarkers at birth, and clinical outcomes at age 1 and 2. Finally, we plan to assess how environmental exposures (perinatal outdoor and indoor pollution, allergens and endotoxin) affect the incidence of allergic sensitization, AD, FA, and risk of asthma. DISCUSSION: The in-depth study of the ARIES birth cohort shall provide crucial information to understand the rising incidence of allergies and asthma in developing countries, and hopefully provide cues on how to prevent and treat these diseases. TRIAL REGISTRATION: clinicaltrials.gov NCT04186949, retrospectively registered on December 5, 2019.

Vitamin D modulates the allergic phenotype of dendritic cells in children with atopic dermatitis.

Vitamin D (VD) deficiency has been associated with increased incidence and severity of atopic dermatitis (AD), but the mechanisms through which VD may ameliorate AD are unclear. We compared the phenotypic characteristics of circulating myeloid and plasmacytoid dendritic cells (mDCs and pDCs, respectively) of children with AD vs healthy controls (HC) and evaluated if VD can modulate the allergic phenotype of circulating DCs in AD patients. Although there was no difference in frequency of circulating DCs between groups, among children with AD there was an inverse correlation between SCORAD and circulating total DCs and mDCs. In AD, serum IgE concentration correlated with FcεRI and surface-bound IgE expression on mDCs and pDCs; pDCs expressing FcεRI and IgE were significantly increased compared to HC. Ex vivo, 1,25(OH)2 D3 significantly decreased FcεRI expression on mDCs and surface-bound IgE on mDCs and pDCs. Oral VD supplementation reduced expression of surface-bound IgE on pDCs in children with AD. In summary, VD decreases the allergic phenotype of circulating DCs in children with AD, a potential mechanism for how VD supplementation may improve AD severity. Future studies are needed to further assess the role of VD supplementation as an immunomodulatory therapy for AD.

[Diagnostic validity of fecal occult blood test in infants with food protein-induced allergic proctocolitis]. / Estudio de validez diagnóstica de la prueba de hemorragia oculta fecal en lactantes con proctocolitis alérgica inducida por proteína alimentaria.

INTRODUCTION: Food protein-induced allergic proctocolitis (FPIAP) is the most frequent presenta tion of non-IgE mediated food allergy (FA). The diagnosis is made by oral food challenge, however, non-invasive diagnostic tests are not available. In Chile, the fecal occult blood test (FOBT) is fre quently used to confirm FPIAP, however, there are no studies that support this practice. OBJECTIVE: To establish the diagnostic validity of FOBT in the evaluation of infants with FPIAP. PATIENTS AND METHOD: Case-control study with prospective recruitment of infants with rectal bleeding and suspicion of FPIAP, and controls were healthy infants, in whom the FOBT was conducted. All cases underwent an elimination diet, after which the diagnosis of FPIAP was confirmed by oral food cha llenge. RESULTS: 25 cases and 29 controls were included without significant differences in age, gen der, type of delivery, feeding, and maternal age. The cases had higher rates of allergic comorbidities, medication use, and family history of allergy. The FOBT was positive in 84% of cases and in 34% of controls (p < 0.001). The sensitivity of the FOBT for the diagnosis of FPIAP was 84%, specificity was 66%, positive predictive value 68%, and the negative predictive value 83%. The area under the ROC curve was 0.75 (CI 95% 0.61-0.88). CONCLUSIONS: Although the FOBT has an adequate sensitivity to diagnose FPIAP in infants with rectal bleeding, this test had abnormal results in more than a third of healthy infants. Therefore, the routine use of FOBT is not recommended for the diagnosis of FPIAP.

Long-term remission of infantile Takayasu arteritis associated with germline CBL syndrome after allogeneic hematopoietic stem cell transplantation: A case report and literature review.

Takayasu arteritis (TA) is a large-vessel vasculitis that rarely presents in infancy. Casitas B-lineage lymphoma (CBL) syndrome is a rare genetic disorder due to heterozygous CBL gene germline pathogenic variants that is characterized by a predisposition to develop juvenile myelomonocytic leukemia (JMML). Vasculitis, including TA, has been reported in several patients. Herein, we describe a patient with CBL syndrome, JMML, and TA, developing long-term remission of this vasculitis after allogeneic hematopoietic stem cell transplant (HSCT), and perform a literature review of CBL syndrome with vasculitis or vasculopathy. We report a female patient with growth delay, developmental issues, and congenital heart disease who was admitted at 14 months of age with massive splenomegaly, lymphadenopathy, fever, and hypertension. Body imaging studies revealed arterial stenosis and wall inflammation of the aorta and multiple thoracic and abdominal branches. Whole exome sequencing revealed a pathogenic variant in CBL with loss of heterozygosity in blood cells, diagnosing CBL syndrome, complicated by JMML and TA. Allogeneic HSCT induced remission of JMML and TA, permitting discontinuation of immunosuppression after 12 months. Six years later, her TA is in complete remission off therapy. A literature review identified 18 additional cases of CBL syndrome with vasculitis or vasculopathy. The pathogenesis of vasculitis in CBL syndrome appears to involve dysregulated T cell function and possibly increased angiogenesis. This case advances the understanding of vascular involvement in CBL syndrome and of the genetic, immune, and vascular interplay in TA, offering insights for treating CBL syndrome and broader TA.

Oral vitamin D modulates the epidermal expression of the vitamin D receptor and cathelicidin in children with atopic dermatitis.

Although vitamin D (VD) is known to have multiple effects on the skin and immunity, its effects on atopic dermatitis (AD) severity remain unclear. We investigated whether oral cholecalciferol (VD3) supplementation changes stratum corneum expression of the vitamin D receptor (vdr), and the epidermal alarmins Cathelicidin Antimicrobial Peptide (camp/LL-37) and Thymic Stromal Lymphopoietin (tslp) in children with AD. We conducted an open-label supplementation study with weekly oral VD3 for six weeks in children with AD. Serum 25-hydroxyvitamin D (25OHD), lesional Staphylococcus aureus colonization, and AD severity evaluated by SCORAD index were evaluated before and after supplementation. Tape stripping (TS) was performed on non-lesional and lesional skin to measure mRNA expression of vdr, camp, and tslp through RT-qPCR and LL-37 peptide by ELISA. Twenty-two children with moderate-severe AD received weekly oral VD3 for six weeks. Total serum 25OHD increased from 45.1 ± 23 to 93.5 ± 24.3 nmoL/L (p < 0.0001), while SCORAD decreased from 41.4 ± 13.5 to 31.5 ± 15.8 (p < 0.0001). After treatment, epidermal gene expression of camp increased significantly in non-lesional (p = 0.014) and lesional (p = 0.0007) tape stripping samples, while vdr only increased in lesional skin samples (p < 0.0001). LL-37 peptide increased significantly only in lesional skin samples (p = 0.008). Gene expression of tslp did not change after oral VD3 treatment. In children with AD, oral VD3 supplementation was associated with improved VD status and AD severity, as well as increased VDR and Cathelicidin expression in lesional skin, which provide mechanistic clues on its effects.

Safety, Tolerability, Bioavailability, and Biological Activity of Inhaled Interferon-α2b in Healthy Adults: The IN2COVID Phase I Randomized Trial.

BACKGROUND AND OBJECTIVES: Interferons have been identified as a potential treatment alternative for coronavirus disease 2019. This study assessed the safety, tolerability, bioavailability, and biological activity of inhaled interferon-α2b (IFN)-α2b in healthy adults. METHODS: A double-blind, randomized, phase I clinical trial was conducted with two cohorts of healthy subjects aged 18-50 years. The first cohort received 2.5 MIU of inhaled IFN-α2b twice daily for 10 days (n = 6) or placebo (n = 3); the second cohort received 5.0 MIU of inhaled IFN-α2b in a similar scheme (n = 6) or placebo (n = 3). The first two doses were administered in an emergency department, then participants completed their treatment at home. Safety was measured through vital signs, new symptoms, and laboratory tests. Tolerability was measured as participants' treatment acceptability. Bioavailability and biological activity were measured from serum IFNα concentrations and real-time quantitative polymerase chain reaction of interferon-induced genes in blood before and after treatments. RESULTS: Exposure to inhaled IFN-α2b at 2.5-MIU or 5-MIU doses did not produce statistically significant changes in participant vital signs, or elicit new symptoms, and standard hematological and biochemical blood measurements were comparable to those recorded in individuals who received placebo. A total of 58 adverse events were observed. All were mild or moderate and did not require medical care. All participants reported very high tolerability towards a twice-daily nebulized treatment for 10 days (98.0, 97.0, and 97.0 in the placebo, 2.5-MIU, and 5-MIU groups, respectively, on a 0- to 100-mm visual analog scale). A dose-dependent mild increase in serum IFN-α concentrations and an increase in serum RNA expression of IFN-induced genes were observed 11 days after treatment (p < 0.05 for all between-group comparisons). CONCLUSIONS: Inhaled IFN-α2b was preliminarily safe and well tolerated, and induced systemic biological activity in healthy subjects. CLINICAL TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT04988217), 3 August, 2021.

Interferon ß-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial.

Background: Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. Methods: A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNß-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 µg subcutaneous pegylated IFNß-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. Findings: 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNß-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNß-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNß-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Interpretation: Based upon the primary analyses, IFNß-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Funding: Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.

Prevalence of filaggrin loss-of-function variants in Chilean population with and without atopic dermatitis.

BACKGROUND: Filaggrin (FLG) loss-of-function variants are major genetic risk factors for atopic dermatitis (AD), but these have not been studied in Latin American populations with and without AD. METHODS: FLG variants R501X and 2282del4 were genotyped in 275 Chilean adults with and without AD from the "Early origins of allergy and asthma" (ARIES) cohort and in 227 patients from an AD cohort based in Santiago, Chile. RESULTS: Among adults in the ARIES cohort, 3.3% were carriers of R501X and 2.9% of 2282del4 variants, all heterozygotes. In this cohort, 6.2% were FLG variant carriers: 11.1% of subjects reporting AD were carriers of FLG variants vs. 5.2% in those without AD (P = 0.13). In this first cohort, FLG variants were not significantly associated with asthma, allergic rhinitis, or food allergy. In the AD cohort, the prevalence of FLG variants was 7% for R501X, 2.2% for the 2282del4 variant, and 9.3% for the combined genotype. In this cohort, FLG variants were present in 15.5% of severe AD vs. 7.1% of mild-to-moderate AD subjects (P = 0.056). Evaluation of Chilean population from both cohorts combined (n = 502) revealed that FLG variants were not significantly associated with AD (OR = 1.92 [95% CI 0.95-3.9], P = 0.067) but were associated with asthma (OR = 2.16 [95% CI 1.02-4.56], P = 0.039). CONCLUSIONS: This is the first study to evaluate FLG loss-of-function variants R501X and 2282del4 in Latin American population, revealing a similar prevalence of these FLG variant carriers to that of European populations. Among Chileans, FLG variants were significantly associated with asthma but not AD.

Vitamin D status and supplementation in Antarctica: a systematic review and meta- analysis.

Living at high latitudes is associated with vitamin D (VD) deficiency. An ideal setting to study this is the Antarctic continent, which has temporary inhabitants, but the magnitude of the effect of living in Antarctica and the effects of VD supplementation on this population remain unclear. We performed a systematic review and meta-analysis to assess the effect of temporary residence in Antarctica and impact of VD supplementation on VD status of this population. Random-effects meta-analyses were performed to assess serum 25-hydroxyvitamin D (25(OH)D) concentration changes after Antarctic residence (13 studies, 294 subjects) and after VD supplementation (5 studies, 213 subjects). Serum 25(OH)D mean difference after temporary residence in Antarctica was -15.0 nmol/L (95%CI: -25.9, -4.2; I²=92%). Subgroup meta-analyses of studies evaluating Antarctic summer and winter stays showed 25(OH)D only decreases when overwintering (winter 25(OH)D change -17.0 nmol/L [95%CI: -24.1, -9.8; I²=83%] vs. summer 25(OH)D change 1.3 nmol/L [95%CI: -14.6, 17.1; I²=86%]). The meta-analysis of VD supplementation studies in Antarctica showed a mean 25(OH)D increase after supplementation of 10.8 nmol/L (95%CI: 3.3, 18.3; I²=88%). In conclusion, VD status significantly worsens after inhabiting Antarctica, particularly when over-wintering. VD supplementation can prevent worsening of VD status and should be considered in this population.

Sleep quality in children with atopic dermatitis during flares and after treatment.

BACKGROUND: Little is known on sleep quality of children with atopic dermtitis (AD) during flares and how treatment impacts their sleep. The purpose of this study is to evaluate variations in sleep quality of children with AD during flares and its response to intensified treatment. MATERIAL AND METHODS: Prospective case-crossover study in 10 children with moderate-severe AD. At baseline, AD severity was assessed using SCORAD and patients were prescribed intensified AD therapy. All subjects were monitored by actigraphy during 14 days and returned for SCORAD assessment. RESULTS: Subjects' age was 5.6 ± 5.3 years; 50% were female. Sleep duration was decreased in all subjects and awakenings were increased in 90%. Parental perception of sleep significantly differed from actigraphy results: parents estimated less sleep duration and less awakenings. Nocturnal sleep efficiency at baseline was reduced in 50%. After intensified treatment, median SCORAD decreased from 58.5 to 31.3 (p=0.005), with significant improvement in sleep loss and pruritus visual analogue scales. Despite improvement of SCORAD and parental perception of sleep loss and pruritus, objective sleep duration and efficiency measured by actigraphy did not vary significantly after intensified treatment. Change in SCORAD, sleep loss and pruritus scales did not correlate significantly with change in sleep duration, efficiency or other actigraphic sleep quality measurements. CONCLUSIONS: Children with moderate-severe AD have sleep quality abnormalities, with decreased sleep duration, low sleep efficiency and increased awakenings. Improvement in AD severity upon intensified AD treatment was associated with improved parental perception of sleep loss, but not of objective sleep quality assessed by actigraphy.

Is there an association between indoor allergens and the severity of atopic dermatitis?

BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with frequent hypersensitivity to allergens. However, the role of exposure to indoor allergens on AD severity is unclear. METHODS: Children aged 0-17 years with active AD from central Chile were recruited; disease severity was evaluated with SCORAD and POEM scores. A home environment survey was applied to parents. Bedroom dust samples were collected for all subjects and analyzed by multiplex assay to quantify dust mite (Der p1, Der f1), dog (Can f1), cat (Fel d1), and alternaria alternata (Alt a1) allergens. RESULTS: Twenty-five children aged 3.9 ± 3.8 years were included. Fifty-two percent were female. Mean SCORAD was 29 ± 14 (range 11-61), and mean POEM was 10.7 ± 6.2. No direct association was found between tobacco exposure, pet ownership, aerosol use, visible dust, or home carpets/rugs with SCORAD (all P > 0.05). Dust samples from all homes had Can f1 and Fel d1 allergens, regardless of pet ownership. Homes that had indoor dogs or cats had significantly higher amounts of these allergens (P < 0.001). Forty percent of homes had dust mite allergens, and none had alternaria alternata. Children with AD living in homes with elevated dust mite and animal dander allergen concentrations had higher SCORAD than those from homes with low allergen concentrations (40 ± 13 vs. 26 ± 13, P = 0.025). CONCLUSIONS: High concentrations of indoor allergens may influence AD severity in children. Further studies assessing indoor allergens and allergen sensitization are warranted to fully evaluate the role of indoor allergens on AD.

Helicobacter pylori pediatric infection changes FcεRI expression in dendritic cells and Treg profile in vivo and in vitro.

H. pylori infection shows an inverse relationship with allergies. Dendritic cells regulate mucosal immune responses including the induction of T regulatory cells which are fundamental in Helicobacter pylori-induced dampening of allergies. In this respect expression of high-affinity IgE receptor (FcεRI) has been associated with a regulatory dendritic cell profile. Therefore we aimed to evaluate possible mechanisms by which H. pylori infection might modify atopy in pediatric patients. Here we show that H. pylori-infected children exhibited both increased expression of FcεRI on peripheral myeloid and plasmacytoid dendritic cells and higher levels of Foxp3 and Latency Associated Peptide on T regulatory cells. Moreover, exposure to H. pylori drove increased FcεRI expression and IL-10 secretion by both pediatric H. pylori-exposed monocyte derived dendritic cells and T cells. Finally, we show a positive correlation between expression of FcεRI in circulating myeloid DCs and total Treg cells, suggesting that in children, H. pylori infection may have a modulating role in atopy, mediated by both altered surface expression of FcεRI on children's DC and an increased T regulatory cell profile.

Humoral and Cellular Autoreactivity to Epidermal Proteins in Atopic Dermatitis.

Atopic dermatitis (AD), a chronic relapsing inflammatory disease of the skin, is an important public health concern affecting 10-20 % of children worldwide. The etiology and pathogenesis of AD involve the interplay of genetic and environmental factors, including abnormalities in skin integrity and a skewed immune system usually driven by a Th2 phenotype in childhood with a switch to Th1 in the chronic phase of disease. Children and adults with AD commonly have elevated IgE levels directed to multiple different antigens, including aeroallergens, food allergens, and microbial proteins. IgE targeting self-antigens from epidermal proteins have been detected in up to 91 % of patients, particularly in severe persistent AD. It has been suggested that the occurrence of autoreactivity develops in early childhood. However, it is not clear yet if autoreactive IgEs in patients with AD are pathogenic or just an epiphenomenon. The fact that these autoantibodies are associated with severity and are not present in other allergic or skin diseases favors the pathogenicity of IgE-mediated autoreactivity in AD. In this review, we evaluate the pathogenesis of AD and the emerging role of autoreactivity to various keratinocyte antigens involving both the humoral and cellular components of the immune system.