Probiotic effects in allergic disease

The increasing prevalence of allergic disease has been linked to reduced microbial exposure in early life. Probiotics have recently been advocated for the prevention and treatment of allergic disease. This article summarises recent publications on probiotics in allergic disease, focusing on clinical studies of prevention or treatment of allergic disease. Studies employing the combined administration of pre-natal and post-natal probiotics suggest a role for certain probiotics (alone or with prebiotics) in the prevention of eczema in early childhood, with the pre-natal component of treatment appearing to be important for beneficial effects. On the other hand, current data are insufficient to support the use of probiotics for the treatment of established allergic disease, although recent studies have highlighted new hope in this area. Probiotic bacteria continue to represent the most promising intervention for primary prevention of allergic disease, and well-designed definitive intervention studies should now be a research priority

Reduced neonatal regulatory T cell response to microbial stimuli associates with subsequent eczema in high risk infants

Background: Regulatory T cells (Treg) play an essential role in early immune programming and shaping the immune response towards a pro‐allergic or tolerant state. We evaluated cord blood Treg and cytokine responses to microbial and non‐microbial stimuli in infants at high risk of allergic disease and their associations with development of allergic disease in the first year. Methods: Cord blood mononuclear cells from 72 neonates were cultured with toll‐like receptors (TLR2) ligands: lipoteichoic acid (LTA) and heat‐killed Lactobacillus rhamnosus GG (HKL); TLR4 ligand: lipopolysaccharide (LPS); ovalbumin (OVA); anti‐CD3; or media for 48 h. Treg numbers and Treg cytokines were assessed in relation to allergic disease outcomes during the first year of life (eczema and atopic sensitization). Results: Infants with eczema (n = 24) had reduced percentages of FoxP3hiCD25hi Treg in LTA (p = 0.01, adj p = 0.005) and HKL (p = 0.04, adj p = 0.02) stimulated cultures as well as reduced IL‐10 (p = 0.01) production following HKL stimulation compared to those without eczema (n = 48). No differences in Treg or cytokine responses to LPS, OVA or anti‐CD3 were seen. Infants who developed sensitization had lower percentages of Treg following TLR2 stimulation (but not other stimuli) compared to non‐sensitized infants. Conclusions: High‐risk children who develop allergic disease in the first year of life have deficient Treg responses to microbial stimuli but not allergen from the time of birth, which may contribute to failure of immune tolerance development in infancy

Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study

Objective To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007

Relationship between breast milk sCD14, TGF-β1 and total IgA in the first month and development of eczema during infancy

INTRODUCTION: The overall beneficial effects of breastfeeding for infants have been well documented, but its role in allergy prevention is controversial. OBJECTIVE: We investigated the relationship between breast milk immunomodulatory factors and subsequent development of eczema and atopic sensitization in the first year of life. METHODS: Day 7 and 28 breast milk samples were collected from mothers carrying infants at high risk of allergic disease. Aqueous-phase breast milk samples were assayed for TGF-β1, sCD14 and total IgA. Infants were assessed for the presence of eczema and atopic sensitization at 12 months of age. The levels of breast milk TGF-β1, sCD14 and total IgA were compared in infants who subsequently developed eczema and sensitization in the first year and those who did not. RESULTS: The levels of breast milk sCD14, total IgA, and TGF-β1 at either day 7 or 28 were not associated with subsequent development of eczema or atopic sensitization during the first year of life. CONCLUSION: Levels of breast milk immune parameters were not associated with eczema outcomes or sensitization in infants at 12 months. This suggests that apparent immunological effects on breast milk immunomodulatory factors may not necessarily lead to clinical benefits, and these immune markers may not be critical determinants of allergic disease in infancy

The ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year: a cohort study

As there is limited knowledge regarding the longitudinal development and early ontogeny of naïve and regulatory CD4(+) T-cell subsets during the first postnatal year, we sought to evaluate the changes in proportion of naïve (thymic and central) and regulatory (resting and activated) CD4(+) T-cell populations during the first postnatal year. Blood samples were collected and analyzed at birth, 6 and 12 months of age from a population-derived sample of 130 infants. The proportion of naïve and regulatory CD4(+) T-cell populations was determined by flow cytometry, and the thymic and central naïve populations were sorted and their phenotype confirmed by relative expression of T cell-receptor excision circle DNA (TREC). At birth, the majority (94%) of CD4(+) T cells were naïve (CD45RA(+)), and of these, ~80% had a thymic naïve phenotype (CD31(+) and high TREC), with the remainder already central naïve cells (CD31(-) and low TREC). During the first year of life, the naïve CD4(+) T cells retained an overall thymic phenotype but decreased steadily. From birth to 6 months of age, the proportion of both resting naïve T regulatory cells (rTreg; CD4(+)CD45RA(+)FoxP3(+)) and activated Treg (aTreg, CD4(+)CD45RA(-)FoxP3(high)) increased markedly. The ratio of thymic to central naïve CD4(+) T cells was lower in males throughout the first postnatal year indicating early sexual dimorphism in immune development. This longitudinal study defines proportions of CD4(+) T-cell populations during the first year of postnatal life that provide a better understanding of normal immune development

Study protocol of a multicentre, randomised, controlled trial evaluating the effectiveness of probiotic and peanut oral immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with oral immunotherapy (OIT) alone and with placebo (the PPOIT-003 study)

Introduction: Peanut allergy is the the most common cause of life-threatening food-induced anaphylaxis. There is currently no effective long-term treatment. There is a pressing need for definitive treatments that improve the quality of life and prevent fatalities. Allergen oral immunotherapy (OIT) is a promising approach, which is effective at inducing desensitisation; however, OIT has a limited ability to induce sustained unresponsiveness (SU). We have previously shown that a novel treatment comprising a combination of the probiotic Lactobacillus rhamnosus CGMCC 1.3724 with peanut OIT (Probiotic Peanut Oral ImmunoTherapy (PPOIT)) is highly effective at inducing SU, with benefit persisting to 4 years after treatment cessation in the majority of initial treatment responders. Here we describe the protocol for a Phase IIb multicentre, double-blind, randomised, controlled trial (PPOIT-003) with dual primary objectives to evaluate the effectiveness of PPOIT at inducing SU (assessed at 8 weeks after treatment cessation) compared with placebo treatment and peanut OIT alone, in children with peanut allergy. Methods and analysis: 200 children 1 to 10 years of age with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited from three tertiary paediatric hospitals in Australia. There are three intervention armsâ PPOIT, peanut OIT alone or placebo. Interventions are administered once daily for 18 months. The dual primary outcomes are: (1) the proportion of children who attain 8-week SU in the PPOIT group versus placebo group and (2) the proportion of children who attain 8-week SU in the PPOIT group versus OIT group. Ethics and dissemination: This study has been approved by the Human Research Ethics Committees at the Royal Children's Hospital (HREC 35246) and the Child and Adolescent Health Service (RGS 2543). Results will be published in peer-reviewed journals and disseminated via presentations at international conferences

Emerging Infections and Pertinent Infections Related to Travel for Patients with Primary Immunodeficiencies

Erratum: J Clin Immunol. 2017 Oct;37(7):693-694. doi: 10.1007/s10875-017-0436-0.In today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text.Peer reviewe

Coupling of hydraulic and electrical transport properties in sandstones

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The 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies

Since the 1990s, the International Union of Immunological Societies (IUIS) PID expert committee (EC), now called Inborn Errors of Immunity Committee, has published every other year a classification of the inborn errors of immunity. This complete catalog serves as a reference for immunologists and researchers worldwide. However, it was unadapted for clinicians at the bedside. For those, the IUIS PID EC is now publishing a phenotypical classification since 2013, which proved to be more user-friendly. There are now 320 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. We herein propose the revised 2017 phenotypic classification, based on the accompanying 2017 IUIS Inborn Errors of Immunity Committee classification