ORCID Profile
0000-0001-7896-2697
Current Organisations
Perth Children's Hospital
,
Royal Australasian College of Physicians
,
Royal College of Pathologists of Australasia
,
Fiona Stanley Hospital
,
Telethon Kids Institute
,
University of Western Australia
,
American Board of Medical Laboratory Immunology
,
PathWest Laboratory Medicine Western Australia
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Publications
Tricho-hepatic-enteric syndrome (THES) without intractable diarrhoea
Publisher: Elsevier BV
Date: 05-2019
The Implications of DNA Methylation on Food Allergy
Publisher: S. Karger AG
Date: 2017
DOI: 10.1159/000479513
Abstract: Food allergy is a major clinical and public health concern worldwide. The risk factors are well defined, however, the mechanisms by which they affect immune development remain largely unknown, and unfortunately the effective treatment or prevention of food allergy is still being researched. Recent studies show that the genes that are critical for the development of food allergy are regulated through DNA methylation. Environmental factors can affect host DNA methylation status and subsequently predispose people to food allergy. DNA methylation is therefore an important mediator of gene-environment interactions in food allergy and key to understanding the mechanisms underlying the allergic development. Indeed, the modification and identification of the methylation levels of specific genetic loci have gained increasing attention for therapeutic and diagnostic application in combating food allergy. In this review, we summarize and discuss the recent developments of DNA methylation in food allergy, including the pathogenesis, therapy, and diagnosis. This review will also summarize and discuss the environmental factors that affect DNA methylation levels in food allergy.
Differences between total IgG and sum of the IgG subclasses in clinical samples
Publisher: Elsevier BV
Date: 12-2013
Acute management of anaphylaxis in pregnancy
Publisher: The Royal Australian College of General Practitioners
Date: 06-2022
Effects of an Amino Acid-Based Formula Supplemented with Two Human Milk Oligosaccharides on Growth, Tolerability, Safety, and Gut Microbiome in Infants with Cow’s Milk Protein Allergy
Publisher: MDPI AG
Date: 30-05-2022
DOI: 10.3390/NU14112297
Abstract: This open-label, non-randomized, multicenter trial (Registration: NCT 03661736) aimed to assess if an amino acid-based formula (AAF) supplemented with two human milk oligosaccharides (HMO) supports normal growth and is well tolerated in infants with a cow’s milk protein allergy (CMPA). Term infants aged 1–8 months with moderate-to-severe CMPA were enrolled. The study formula was an AAF supplemented with 2′-fucosyllactose (2′-FL) and lacto-N-neotetraose (LNnT). Infants were fed the study formula for 4 months and were offered to remain on the formula until 12 months of age. Tolerance and safety were assessed throughout the trial. Out of 32 infants (mean age 18.6 weeks 20 (62.5%) male), 29 completed the trial. During the 4-month principal study period, the mean weight-for-age Z score (WAZ) increased from −0.31 at the baseline to +0.28 at the 4-months’ follow-up. Linear and head growth also progressed along the WHO child growth reference, with a similar small upward trend. The formula was well tolerated and had an excellent safety profile. When comparing the microbiome at the baseline to the subsequent visits, there was a significant on-treatment enrichment in HMO-utilizing bifidobacteria, which was associated with a significant increase in fecal short-chain fatty acids. In addition, we observed a significant reduction in the abundance of fecal Proteobacteria, suggesting that the HMO-supplemented study formula partially corrected the gut microbial dysbiosis in infants with CMPA.
PrEggNut Study: protocol for a randomised controlled trial investigating the effect of a maternal diet rich in eggs and peanuts from <23 weeks’ gestation during pregnancy to 4 months’ lactation on
Publisher: BMJ
Date: 06-2022
DOI: 10.1136/BMJOPEN-2021-056925
Abstract: Clinical studies supported by immunological data indicate early life intervention strategies to be promising in reducing the growing global burden of food allergies. The events that predispose to food allergy, including the induction of allergen-specific immune responses, appear to be initiated early in development. Early exposure to food allergens in utero and via breast milk is likely to be important in initiating oral tolerance. We aim to determine the effectiveness of higher maternal food allergen consumption during pregnancy and lactation on infant food allergy outcomes. This is a multisite, parallel, two-arm (1:1 allocation), single-blinded (outcome assessors, statistical analyst and investigators), randomised controlled trial. Pregnant women ( weeks’ gestation) whose (unborn) infants have at least two biological family members (mother, father or siblings) with medically diagnosed allergic disease are eligible to participate. After obtaining written informed consent, pregnant women are randomised to either a high egg and peanut diet (at least 6 eggs and 60 peanuts per week) or standard (low) egg and peanut diet (no more than 3 eggs and 30 peanuts per week). The women are asked to follow their allocated diet from weeks’ gestation to 4 months’ lactation. The primary outcome is food challenge proven IgE-mediated egg and/or peanut allergy in the infants at 12 months of age. Key secondary outcomes include infant sensitisation to egg and/or peanut and infant eczema. Our target s le size is 2136 women. Analyses will be performed on an intention-to-treat basis according to a pre-specified statistical analysis plan. Ethical approval has been granted from the Women’s and Children’s Health Network Human Research Ethics Committee (approval number HREC/18/WCHN/42). Trial results will be presented at scientific conferences and published in peer-reviewed journals. Australian New Zealand Clinical Trials Registry ACTRN12618000937213.
Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome
Publisher: Elsevier BV
Date: 04-2023
DOI: 10.1016/J.JACI.2022.09.002
Abstract: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%) increased frequencies of double-negative (CD4-CD8-) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.
Germline-activating mutations in PIK3CD compromise B cell development and function
Publisher: Rockefeller University Press
Date: 17-07-2018
DOI: 10.1084/JEM.20180010
Abstract: Gain-of-function (GOF) mutations in PIK3CD, encoding the p110δ subunit of phosphatidylinositide 3-kinase (PI3K), cause a primary immunodeficiency. Affected in iduals display impaired humoral immune responses following infection or immunization. To establish mechanisms underlying these immune defects, we studied a large cohort of patients with PIK3CD GOF mutations and established a novel mouse model using CRISPR/Cas9-mediated gene editing to introduce a common pathogenic mutation in Pik3cd. In both species, hyperactive PI3K severely affected B cell development and differentiation in the bone marrow and the periphery. Furthermore, PI3K GOF B cells exhibited intrinsic defects in class-switch recombination (CSR) due to impaired induction of activation-induced cytidine deaminase (AID) and failure to acquire a plasmablast gene signature and phenotype. Importantly, defects in CSR, AID expression, and Ig secretion were restored by leniolisib, a specific p110δ inhibitor. Our findings reveal key roles for balanced PI3K signaling in B cell development and long-lived humoral immunity and memory and establish the validity of treating affected in iduals with p110δ inhibitors.
Four-hour access targets for emergency departments: Potential negative implications for the work practices and clinical training of junior doctors
Publisher: Wiley
Date: 12-2011
Outcome of mixed nut biscuit challenges in low‐risk patients who are on tree nut exclusion diet
Publisher: Wiley
Date: 11-09-2015
DOI: 10.1111/PAI.12437
Critique on the quantitative nature of IgE antibody measurements
Publisher: Elsevier BV
Date: 11-2015
Dysfunctional gut microbiome networks in childhood ige‐mediated food allergy
Publisher: MDPI AG
Date: 19-02-2021
DOI: 10.3390/IJMS22042079
Abstract: The development of food allergy has been reported to be related with the changes in the gut microbiome, however the specific microbe associated with the pathogenesis of food allergy remains elusive. This study aimed to comprehensively characterize the gut microbiome and identify in idual or group gut microbes relating to food-allergy using 16S rRNA gene sequencing with network analysis. Faecal s les were collected from children with IgE-mediated food allergies (n = 33) and without food allergy (n = 27). Gut microbiome was profiled by 16S rRNA gene sequencing. OTUs obtained from 16S rRNA gene sequencing were then used to construct a co-abundance network using Weighted Gene Co-expression Network Analysis (WGCNA) and mapped onto Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We identified a co-abundance network module to be positively correlated with IgE-mediated food allergy and this module was characterized by a hub taxon, namely Ruminococcaceae UCG-002 (phylum Firmicutes). Functional pathway analysis of all the gut microbiome showed enrichment of methane metabolism and glycerolipid metabolism in the gut microbiome of food-allergic children and enrichment of ubiquinone and other terpenoid-quinone biosynthesis in the gut microbiome of non-food allergic children. We concluded that Ruminococcaceae UCG-002 may play determinant roles in gut microbial community structure and function leading to the development of IgE-mediated food allergy.
Management of adverse events related to new cancer immunotherapy (immune checkpoint inhibitors)
Publisher: AMPCo
Date: 11-2016
DOI: 10.5694/MJA16.00586
Abstract: New immunotherapies have significantly improved survival in certain advanced cancers in recent years, particularly metastatic melanoma and lung cancer. The most effective of these therapies are the immune checkpoint inhibitors (ICIs) such as ipilimumab, nivolumab and pembrolizumab. The use of ICIs will continue to increase in the coming years as evidence of their benefit in a range of other cancers builds. ICIs are associated with novel immune-related adverse events (irAEs), which can involve a wide range of organs. The most common irAEs involve the skin (rash, pruritus), gastrointestinal tract (diarrhoea, colitis) and endocrine system (thyroid, pituitary). While severity is generally mild, life-threatening complications can occur if not recognised and treated promptly. Due to the erse manifestations of irAEs, patients may present to doctors who are not familiar with these drugs, which creates the potential for delays in management. Management of irAEs depends on severity and the organ affected. Systemic steroids are often required and ICI therapy may be withheld or discontinued. Additional immunosuppressive medications may be necessary in steroid-refractory cases. This review provides an overview of the potential toxicities and their management for general clinicians. Broader awareness of these issues among medical professionals will hopefully reduce unnecessary delays in diagnosis and treatment. Patient and carer education regarding irAEs is extremely important patients and carers should be advised to seek urgent medical attention if required.
Cosensitization to orange seed and cashew nut
Publisher: Elsevier BV
Date: 09-2011
Long-term, open-label extension study of the efficacy and safety of epicutaneous immunotherapy for peanut allergy in children: PEOPLE 3-year results
Publisher: Elsevier BV
Date: 10-2020
Activating PIK3CD mutations impair human cytotoxic lymphocyte differentiation and function and EBV immunity
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JACI.2018.04.030
Abstract: Germline gain-of function (GOF) mutations in PIK3CD, encoding the catalytic p110δ subunit of phosphoinositide 3-kinase (PI3K), result in hyperactivation of the PI3K-AKT-mechanistic target of rapamycin pathway and underlie a novel inborn error of immunity. Affected subjects exhibit perturbed humoral and cellular immunity, manifesting as recurrent infections, autoimmunity, hepatosplenomegaly, uncontrolled EBV and/or cytomegalovirus infection, and increased incidence of B-cell lymphoproliferation, lymphoma, or both. Mechanisms underlying disease pathogenesis remain unknown. Understanding the cellular and molecular mechanisms underpinning inefficient surveillance of EBV-infected B cells is required to understand disease in patients with PIK3CD GOF mutations, identify key molecules required for cell-mediated immunity against EBV, and develop immunotherapeutic interventions for the treatment of this and other EBV-opathies. We studied the consequences of PIK3CD GOF mutations on the generation, differentiation, and function of CD8 PIK3CD GOF total and EBV-specific CD8 PIK3CD GOF mutations aberrantly induce exhaustion, senescence, or both and impair cytotoxicity of CD8
Children with nut allergies have impaired gene expression of Toll‐like receptors pathway
Publisher: Wiley
Date: 08-04-2020
DOI: 10.1111/PAI.13246
Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial
Publisher: Elsevier BV
Date: 03-2022
SmartStartAllergy: a novel tool for monitoring food allergen introduction in infants.
Publisher: AMPCo
Date: 04-2020
DOI: 10.5694/MJA2.50484
A Novel Targeted Amplicon Next-Generation Sequencing Gene Panel for the Diagnosis of Common Variable Immunodeficiency Has a High Diagnostic Yield
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.JMOLDX.2022.02.007
Abstract: With the advent of next-generation sequencing (NGS), monogenic forms of common variable immunodeficiency (CVID) have been increasingly described. Our study aimed to identify disease-causing variants in a Western Australian CVID cohort using a novel targeted NGS panel. Targeted licon NGS was performed on 22 unrelated subjects who met the formal European Society for Immunodeficiencies-Pan-American Group for Immunodeficiency diagnostic criteria for CVID and had at least one of the following additional criteria: disease onset at age <18 years, autoimmunity, low memory B lymphocytes, family history, and/or history of lymphoproliferation. Candidate variants were assessed by in silico predictions of deleteriousness, comparison to the literature, and classified according to the American College of Medical Genetics and Genomics-Association for Molecular Pathology criteria. All detected genetic variants were verified independently by an external laboratory, and additional functional studies were performed if required. Pathogenic or likely pathogenic variants were detected in 6 of 22 (27%) patients. Monoallelic variants of uncertain significance were also identified in a further 4 of 22 patients (18%). Pathogenic variants, likely pathogenic variants, or variants of uncertain significance were found in TNFRSF13B, TNFRSF13C, ICOS, AICDA, IL21R, NFKB2, and CD40LG, including novel variants and variants with unexpected inheritance pattern. Targeted licon NGS is an effective tool to identify monogenic disease-causing variants in CVID, and is comparable or superior to other NGS methods. Moreover, targeted licon NGS identified patients who may benefit from targeted therapeutic strategies and had important implications for family members.
Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy
Publisher: Elsevier BV
Date: 02-2022
The 10 warning signs
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 12-2012
P33: EARLY PEANUT IMMUNOTHERAPY IN CHILDREN (EPIC) – A PRAGMATIC PEANUT ORAL IMMUNOTHERAPY PROTOCOL FOR CHILDREN UNDER 5 YEARS OF AGE
Publisher: Wiley
Date: 10-2022
DOI: 10.1111/IMJ.32_15894
Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy
Publisher: Massachusetts Medical Society
Date: 11-05-2023
Anticytokine Autoantibodies: Association with Infection and Immune Dysregulation
Publisher: MDPI AG
Date: 15-01-2016
DOI: 10.3390/ANTIB5010003
Activated PI3Kδ breaches multiple B cell tolerance checkpoints and causes autoantibody production
Publisher: Rockefeller University Press
Date: 16-12-2019
DOI: 10.1084/JEM.20191336
Abstract: Antibody-mediated autoimmune diseases are a major health burden. However, our understanding of how self-reactive B cells escape self-tolerance checkpoints to secrete pathogenic autoantibodies remains incomplete. Here, we demonstrate that patients with monogenic immune dysregulation caused by gain-of-function mutations in PIK3CD, encoding the p110δ catalytic subunit of phosphoinositide 3-kinase (PI3K), have highly penetrant secretion of autoreactive IgM antibodies. In mice with the corresponding heterozygous Pik3cd activating mutation, self-reactive B cells exhibit a cell-autonomous subversion of their response to self-antigen: instead of becoming tolerized and repressed from secreting autoantibody, Pik3cd gain-of-function B cells are activated by self-antigen to form plasmablasts that secrete high titers of germline-encoded IgM autoantibody and hypermutating germinal center B cells. However, within the germinal center, peripheral tolerance was still enforced, and there was selection against B cells with high affinity for self-antigen. These data show that the strength of PI3K signaling is a key regulator of pregerminal center B cell self-tolerance and thus represents a druggable pathway to treat antibody-mediated autoimmunity.
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
Publisher: BMJ
Date: 09-2020
DOI: 10.1136/BMJOPEN-2019-035871
Abstract: 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. 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 arms—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. 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. ACTRN12616000322437.
Etoposide phosphate hypersensitivity overcome using a desensitisation programme enabling optimal therapy for relapsed Hodgkin lymphoma
Publisher: Springer Science and Business Media LLC
Date: 31-10-2016
DOI: 10.1038/BMT.2016.288
A paediatric case of exercise-augmented anaphylaxis following bee pollen ingestion in Western Australia
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2022
P43: SMARTSTARTALLERGY – A NOVEL TOOL FOR MONITORING PARENT‐REPORTED IGE FOOD ALLERGY IN INFANTS
Publisher: Wiley
Date: 10-2022
DOI: 10.1111/IMJ.42_15894
Successful treatment of ACE inhibitor‐induced angioedema with icatibant, a bradykinin B2 receptor antagonist
Publisher: Wiley
Date: 06-2015
DOI: 10.5694/MJA15.01015
Related Organisations
American Board Of Medical Laboratory Immunology
Location: United States of America
Related Funding Activities
No related grants have been discovered for Michael O'Sullivan.