Increases in plasma IgG4/IgE with trilipid vs paraffin/petrolatum-based emollients for dry skin/eczema.
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SUBMITTER: Sindher S
PROVIDER: S-EPMC8078833 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Introduction:Atopic dermatitis/eczema affects around 20% of children and is characterised by inflamed, dry, itchy skin. Guidelines recommend 'leave-on' emollients that are applied directly to the skin to add or trap moisture and used regularly, they can soothe, enhance the skin barrier and may prevent disease 'flares'. However, the suitability of the many different emollients varies between people and there is little evidence to help prescribers and parents and carers decide which type to try first.Methods and analysis:Design: pragmatic, multicentre, individually randomised, parallel group superiority trial of four types of emollient (lotions, creams, gel or ointments).Setting:general practitioner surgeries in England.Participants:children aged over 6 months and less than 12 years with mild-to-severe eczema and no known sensitivity to study emollients.Interventions:study-approved lotion, cream, gel or ointment as the only leave-on emollient for 16 weeks, with directions to apply twice daily and as required. Other treatments, such as topical corticosteroids, used as standard care.Follow-up:52 weeks.Primary outcome:validated patient-orientated eczema measure measured weekly for 16 weeks.Secondary outcomes:eczema signs (Eczema Area Severity Index) by masked researcher, treatment use, parent satisfaction, adverse events, child and family quality of life (Atopic Dermatitis Quality of Life, Child Health Utility 9D and Dermatitis Family Impact).Sample size:520 participants (130 per group).Analysis:intention-to-treat using linear mixed models for repeated measures.Nested qualitative study: audio-recording of sample of baseline appointments and up to 60 interviews with participants at 4 and 16 weeks, interviews to be transcribed and analysed thematically.Ethics and dissemination:Ethics approval granted by the NHS REC (South West - Central Bristol Research Ethics Committee 17/SW/0089). Findings will be presented at conferences, published in open-access peer-reviewed journals and the study website; and summaries shared with key stakeholders.Trial registration number:ISRCTN84540529.
| S-EPMC6858146 | biostudies-literature
Project description:BackgroundSerum inhibition of allergen-specific IgE has been associated with competing IgG4 and non-specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth-associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low-income countries.MethodsAmong community residents of Ugandan rural Schistosoma mansoni (Sm)-endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non-asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)-specific, Schistosoma egg antigen (SEA)-specific and allergen (house dust mite [HDM] and German cockroach)-specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural-urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.ResultsTotal IgE, total IgG4 and SWA-, SEA- and allergen-specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen-specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma-specific IgG4, allergen-specific IgG4/IgE ratios and total IgE/allergen-specific IgE ratios. Asthmatic schoolchildren, compared with non-asthmatic controls, had significantly higher levels of total and allergen-specific IgE, but lower ratios of allergen-specific IgG4/IgE and total IgE/allergen-specific IgE.Conclusions and clinical relevanceOur immuno-epidemiological data support the hypothesis that the IgG4-IgE balance and the total IgE-allergen-specific IgE balance are more important than absolute total, helminth- or allergen-specific antibody levels in inhibition of allergies in the tropics.
| S-EPMC7610822 | biostudies-literature
Project description:BACKGROUND:Atopic dermatitis (AD) is a common, chronic skin disorder often beginning in infancy. Skin barrier dysfunction early in life serves as a central event in the pathogenesis of AD. In infants at high risk of developing AD, preventative application of lipid-rich emollients may reduce the risk of developing AD. This study aims to measure the effectiveness of this intervention in a population not selected for risk via a pragmatic, randomized, physician-blinded trial in the primary care setting. METHODS:Infant-parent dyads are recruited from a primary care practice participating through one of four practice-based research networks in Oregon, Colorado, Wisconsin, and North Carolina. Eligible dyads are randomized to the intervention (daily use of lipid-rich emollient) or the control (no emollient) group (n =?625 infants in each) and are followed for 24?months. The primary outcome is the cumulative incidence of physician-diagnosed AD and secondary outcomes include caregiver-reported measures of AD and development of other atopic diseases. Data collection occurs via chart review and surveys, with no study visits required. Data will be analyzed utilizing intention-to-treat principles. DISCUSSION:AD is a common skin condition in infants that affects quality of life and is associated with the development of other atopic diseases. If a safe intervention, such as application of lipid-rich emollients, in the general population effectively decreases AD prevalence, this could alter the guidance given by providers regarding routine skin care of infants. Because of the pragmatic design, we anticipate that this trial will yield generalizable results. TRIAL REGISTRATION:ClinicalTrials.gov: NCT03409367. Registered on 11 February 2018.
| S-EPMC7057622 | biostudies-literature
Project description:Immunoepidemiological studies from endemic areas have revealed age-dependent resistance correlation with increased level of IgE and decreased level of IgG4 antibodies in responses to schistosomes' soluble worm antigen. However, there have been limited studies on analyses of major antigens that provoke IgE and IgG4 immune response during chronic stage of schistosomiasis. In this study, for the first time, immunoproteomics approach has been applied to identify S. japonicum worm antigens in liquid fractions that are recognized by IgE and IgG4 antibody using plasma from chronically infected population. ProteomeLabPF 2D fractionated 1-D and 2-D fractions of SWA antigens were screened using pooled high IgE/IgG4 reactive plasma samples by dot-blot technique. In 1-D fractions, IgE isotype was detected by fewer antigenic fractions (43.2%). The most recognized isotype was IgG3 (79.5%) followed by IgG1 (75.0%) and IgG4 (61.4%). Liquid chromatography MS/MS protein sequencing of reactive 2-D fractions revealed 18 proteins that were identified, characterized and gene ontology categories determined. 2-D fractions containing proteins such as zinc finger, RanBP2-type, domain-containing protein were strongly recognized by IgE and moderately by IgG4 whereas fractions containing proteins such as ubiquitin-conjugating enzyme and cytosolic II 5'-nucleotidase strongly recognizing by IgG subclasses (IgG1, IgG3 and IgG4) but not IgE. By this study, a simple and reproducible proteomic method has been established to identify major immunoreactive S. japonicum antigens. It is anticipated that this will stimulate further research on the immunogenicity and protective potential of proteins identified as well as discovery of novel compounds that have therapeutic importance.
| S-EPMC3521053 | biostudies-literature
Project description:IntroductionHealthcare professionals tend to recommend emollients based primarily on patient/consumer preference and cost, with cheaper options assumed to be therapeutically equivalent. The aim of this study was therefore to compare the effects on skin hydration of two emollients prescribed in the UK, Doublebase Dayleve™ gel (DELP) and a cheaper alternative, Zerobase Emollient™ cream (ZBC).MethodsThis was a single-centre, randomised, double-blind, concurrent bi-lateral (within-patient) comparison in 18 females with atopic eczema and dry skin on their lower legs. DELP gel and ZBC cream were each applied to one lower leg twice daily for 4 days and on the morning only on day 5. The efficacy of both products was assessed by hydration measurements using a Corneometer CM825 probe (Courage-Khazaka Electronic). The measurements were made three times daily on days 1 to 5. The primary efficacy variable was the area under the curve (AUC) of the change from baseline corneometer readings over the 5 days.ResultsSkin hydration using DELP gel was significantly higher than using ZBC cream (p < 0.0001). The cumulative increase in skin hydration observed for DELP gel was substantial and long lasting. In contrast, for ZBC cream, there was no significant improvement of the cumulative skin hydration as measured by the AUC (p = 0.22).ConclusionDELP gel achieved substantial, long-lasting and cumulative skin hydration, whilst ZBC cream achieved no measurable improvement in skin hydration compared to before treatment. Healthcare professionals should be aware that different emollients can perform differently.FundingDermal Laboratories Ltd.Trial registrationEudraCT number:2014-001026-16.
| S-EPMC5574740 | biostudies-literature
Project description:Dry and eczema-prone skin conditions such as atopic dermatitis and xerotic eczema primarily indicate an impaired skin barrier function, which leads to chronic pruritus. Here, we investigated the effects of a novel emollient containing H.ECMTM liposome, which contains a soluble proteoglycan in combination with hydrolyzed collagen and hyaluronic acid. A prospective, single-arm study was conducted on 25 participants with mild atopic dermatitis or dry skin to assess the hydration and anti-inflammatory effect of the novel emollient applied daily over four weeks. All efficacy parameters, including itching severity, transepidermal water loss, and skin hydration, improved significantly after four weeks. The in vitro and ex vivo studies confirmed the restoration of the skin's barrier function. The study revealed the clinical and laboratory efficacy of H.ECMTM liposome in reducing itching and improving the skin's barrier integrity. Thus, the use of H.ECMTM liposome can be considered a therapeutic option for dry and eczema-prone skin.
| S-EPMC8508667 | biostudies-literature
Project description:BackgroundIn addition to allergen-specific IgE (sIgE), allergen-specific IgG4 (sIgG4) antibodies are also involved in the immune response resulting from an allergen exposure. The aim of our study was to analyze sIgE and sIgG4 patterns in the most common allergic disorders: bronchial asthma, upper airway disorders and atopic dermatitis.MethodsIn this study a screening analysis of blood serum samples from 673 patients aged from 6 months to 17 years with different allergic entities was performed on microarrays. sIgE and sIgG4 levels to the most common allergens were estimated.ResultssIgE response to most pollen allergens is more strongly associated with respiratory diseases than with atopic dermatitis, while sIgE responses to cat and dog dander are more strongly associated with bronchial asthma than with atopic dermatitis and upper airway disorders such as rhinosinusitis and allergic rhinitis. A lower prevalence of sIgG4 to pollen allergens in cases of atopic dermatitis is observed compared with that in cases of asthma and upper airway disorders. Analyzing all the allergic disorders, one can see that sIgG4 response to inhalant allergens is strongly associated with sensitization to the corresponding allergen.ConclusionAllergen-specific IgE and IgG4 patterns that are relevant to concrete allergic diseases differ by sIgE and sIgG4 prevalences to defined allergens.
| S-EPMC6276220 | biostudies-literature
Project description:BackgroundPatients with peanut allergy have highly stable pathologic antibody repertoires to the immunodominant B-cell epitopes of the major peanut allergens Ara h 1 to 3.ObjectiveWe used a peptide microarray technique to analyze the effect of treatment with peanut oral immunotherapy (OIT) on such repertoires.MethodsMeasurements of total peanut-specific IgE (psIgE) and peanut-specific IgG(4) (psIgG(4)) were made with CAP-FEIA. We analyzed sera from 22 patients with OIT and 6 control subjects and measured serum specific IgE and IgG(4) binding to epitopes of Ara h 1 to 3 using a high-throughput peptide microarray technique. Antibody affinity was measured by using a competitive peptide microarray, as previously described.ResultsAt baseline, psIgE and psIgG(4) diversity was similar between patients and control subjects, and there was broad variation in epitope recognition. After a median of 41 months of OIT, polyclonal psIgG(4) levels increased from a median of 0.3 μg/mL (interquartile range [25% to 75%], 0.1-0.43 μg/mL) at baseline to 10.5 μg/mL (interquartile range [25% to 75%], 3.95-45.48 μg/mL; P < .0001) and included de novo specificities. psIgE levels were reduced from a median baseline of 85.45 kU(A)/L (23.05-101.0 kU(A)/L) to 7.75 kU(A)/L (2.58-30.55 kU(A)/L, P < .0001). Affinity was unaffected. Although the psIgE repertoire contracted in most OIT-treated patients, several subjects generated new IgE specificities, even as the total psIgE level decreased. Global epitope-specific shifts from IgE to IgG(4) binding occurred, including at an informative epitope of Ara h 2.ConclusionOIT differentially alters Ara h 1 to 3 binding patterns. These changes are variable between patients, are not observed in control subjects, and include a progressive polyclonal increase in IgG(4) levels, with concurrent reduction in IgE amount and diversity.
| S-EPMC3529994 | biostudies-literature
Project description:BackgroundOral immunotherapy (OIT) with peanut (Arachis hypogaea) allergen powder-dnfp (PTAH; Aimmune Therapeutics) is an FDA-approved treatment to desensitize peanut allergic participants.ObjectiveHere we assessed shifts in IgE and IgG4 binding to peanut allergens and their epitopes recognized by United States (US) peanut allergic participants (n = 20) enrolled in phase 3 PTAH OIT clinical trials.MethodsPre- and post- trial participant sera were collected approximately 12 months apart and tested for IgE binding to intact peanut proteins via ImmunoCAP ISAC immunoassays. IgE and IgG4 linear epitopes were identified based on binding to synthetic overlapping 15-mer linear peptides of 10 peanut allergens (Ara h 1-11) synthesized on microarray slides.ResultsStatistically significant decreases in IgE binding were identified for intact Ara h 2, 3, and 6, and known and newly identified IgE epitopes were shown to exhibit shifts towards IgG4 binding post-OIT, with most linear peptides having increased IgG4 binding after treatment with PTAH. While PTAH does not seem to alter the actual peptide binding patterns significantly after one year of treatment, the IgE and IgG4 binding ratios and intensity are altered.ConclusionAt a population level, the linear IgE and IgG4 epitopes of 10 peanut allergens overlap and that increase in IgG4 with OIT results in displacement of IgE binding to both conformational and linear epitopes. Furthermore, it appears as though the increase in IgG4 is more important to achieve desensitization at the 12-month timepoint than the decrease in IgE. This type of knowledge can be useful in the identification of IgE and IgG4-binding allergen and peptide biomarkers that may indicate desensitization or sustained unresponsiveness of allergic individuals to peanut.
| S-EPMC10717846 | biostudies-literature
Project description:Immunoglobulin G4 (IgG4)-related disease is characterized by elevated serum IgG4 levels and increased numbers of IgG4-positive cells. However, its pathogenesis is not fully understood. We previously suggested that mast cells may play an important role in IgG4-related disease. In this study, we confirmed the characteristics of mast cells in IgG4-related lymphadenopathy by using immunohistochemistry and dual immunofluorescence. We analyzed 23 cases of IgG4-related lymphadenopathy and compared them with 23 cases of non-specific lymphoid hyperplasia. The majority of patients with IgG4-related lymphadenopathy had cervical lesions with involvement of other organs. Immunohistologically, mast cells with strong cytoplasmic staining for immunoglobulin E and high affinity immunoglobulin E receptor were significantly increased in IgG4-related lymphadenopathy as compared to those in non-specific lymphoid hyperplasia (mean: 3.83?±?3.99 cells per high power field and 7.14?±?8.21 cells per high power field, respectively; P?=?0.007 and P?=?0.011). In addition, dual immunofluorescence assay showed that immunoglobulin E and high affinity immunoglobulin E receptor staining exhibited a cytoplasmic granular pattern in IgG4-related lymphadenopathy, suggesting internalization of the antibodies and receptors. Our findings showed that mast cell activation might be involved in the pathogenesis of IgG4-related disease.
| S-EPMC5854596 | biostudies-literature