Inborn Errors of the Immune System Associated With Atopy

Nelson, Ryan; Geha, Raif S.; McDonald, Douglas R.

doi:10.3389/fimmu.2022.860821

Cited by 12 publications

(23 citation statements)

References 137 publications

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“…These conditions and their known culprit genes include Hyper IgE syndrome (STAT3, DOCK8), CARMIL2 deficiency (CARMIL2), Omenn syndrome (RAG1, RAG2), Netherton syndrome (SPINK5), Wiskott-Aldrich syndrome (WAS), adenosine deaminase severe combined immunodeficiency (ADA-SCID) (ADA), immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome (FOXP3), CARD11-associated atopy with dominant interference of NF-κB signaling (CADINS) disease (CARD11), congenital disorders of glycosylation (PGM3), prolidase deficiency (PEPD), severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome (DSG1, DSP), and growth hormone insensitivity (GHI) syndrome with immunodeficiency (STAT5B). [116][117][118][119][120][121][122][123][124][125][126][127][128][129] Recently, GoF STAT6 variants have been associated with a novel autosomal dominant allergic disorder featuring early-onset allergic immune dysregulation with widespread refractory AD, hypereosinophilia with eosinophilic esophagitis, high serum IgE, food allergies, and brain vascular anomalies. 130 Although rare, these genetic disorders should be considered in the differential diagnosis of AD, especially in patients where the constellation of findings exceeds atopy.…”

Section: Genetic Disorders With Ad-like Lesionsmentioning

confidence: 99%

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Chong¹,

Visitsunthorn²,

Ong³

2022

JAA

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Atopic dermatitis (AD) is one of the most common skin conditions in humans. AD affects up to 20% of children worldwide and results in morbidity for both patients and their caregivers. The basis of AD is an interplay between genetics and the environment characterized by immune dysregulation. A myriad of mutations that compromise the skin barrier and/or immune function have been linked to AD. Of these, filaggrin gene ( FLG ) mutations are the most evidenced. Many other mutations have been implicated in isolated studies that are often unreplicated, creating an archive of genes with potential but unconfirmed relevance to AD. Harnessing big data, polygenic risk scores (PRSs) and genome-wide association studies (GWAS) may provide a more practical strategy for identifying the genetic signatures of AD. Epigenetics may also play a role. Staphylococcus aureus is the most evidenced microbial contributor to AD. Cutaneous dysbiosis may result in over-colonization by pathogenic strains and aberrant skin immunity and inflammation. Aeroallergens, air pollution, and climate are other key environmental contributors to AD. The right climate and/or commensals may improve AD for some patients.

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Section: Genetic Disorders With Ad-like Lesionsmentioning

confidence: 99%

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Chong¹,

Visitsunthorn²,

Ong³

2022

JAA

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“…FLG and DSG1 are marked in italics, as they are not necessarily associated with IEI but are monogenic defects supporting the pathogenic category. We have grouped thymic development disorders and decreased T cell repertoire diversity [4 ▪ ,5,6 ▪ ,26,28–41].…”

Section: Methodsmentioning

confidence: 99%

“…The dates these disorders were reported is shown in Fig. 1, and clinical phenotypes summarized in Table 1, adapted from Lyons et al [5], and Nelson et al [6 ] and IUIS update [4 & ].…”

Section: Methodsmentioning

confidence: 99%

Atopic manifestations of inborn errors of immunity

Sams,

Wijetilleka,

Ponsford

et al. 2023

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Allergy and atopic features are now well recognized manifestations of many inborn errors of immunity (IEI), and indeed may be the hallmark in some, such as DOCK8 deficiency. In this review, we describe the current IEI associated with atopy, using a comprehensive literature search and updates from the IUIS highlighting clinical clues for underlying IEI such as very early onset of atopic disease or treatment resistance to enable early and accurate genetic diagnosis. Recent findings We focus on recently described genes, their categories of pathogenic mechanisms and the expanding range of potential therapies. Summary We highlight in this review that patients with very early onset or treatment resistant atopic disorders should be investigated for an IEI, as targeted and effective therapies exist. Early and accurate genetic diagnosis is crucial in this cohort to reduce the burden of disease and mortality.

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“…The mechanisms underlying the immunological alterations responsible for the atopic features observed in Os are still a matter of debate. Lymphopenia-induced homeostatic proliferation, poor thymic control of autoreactive lymphocytes, defective Treg and Th2 skewed response have been reported ( 100 ).…”

Section: Other Genesmentioning

confidence: 99%

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

et al. 2023

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Inborn errors of immunity associated with atopy (IEIs-A) are a group of inherited monogenic disorders that occur with immune dysregulation and frequent skin involvement. Several pathways are involved in the pathogenesis of these conditions, including immune system defects, alterations of skin barrier and metabolism perturbations. Current technological improvements and the higher accessibility to genetic testing, recently allowed the identification of novel molecular pathways involved in IEIs-A, also informing on potential tailored therapeutic strategies. Compared to other systemic therapy for skin diseases, biologics have the less toxic and the best tolerated profile in the setting of immune dysregulation. Here, we review IEIs-A with skin involvement focusing on the tailored therapeutic approach according to their pathogenetic mechanism.

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Inborn Errors of the Immune System Associated With Atopy

Cited by 12 publications

References 137 publications

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Genetic/Environmental Contributions and Immune Dysregulation in Children with Atopic Dermatitis

Atopic manifestations of inborn errors of immunity

Tailored treatments in inborn errors of immunity associated with atopy (IEIs-A) with skin involvement

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