Primary atopic disorders

Lyons, Jonathan J.; Milner, Joshua D.

doi:10.1084/jem.20172306

Cited by 77 publications

(89 citation statements)

References 177 publications

(217 reference statements)

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“…IgE was first isolated in 1966 [19, 20, 55, 56], in the same year as Job’s syndrome was first described. The existence of IgE was actually suspected 45 years before its physical discovery [57].…”

Section: Ige and Its Productionmentioning

confidence: 99%

“…Conversely, the discovery of genetic causes of HIES, or perhaps eventually of isolated IgE deficiency, may shed light on the mechanisms controlling human IgE production. A very elegant review on inborn errors of atopic disorders and their relationship to abnormal IgE production was recently published [55]. …”

Section: Ige and Its Productionmentioning

confidence: 99%

“…HIES patients with PGM3 deficiency probably have a T-cell disorder with Th2 bias, similar to that in DOCK8-deficient patients. It has been shown that the paucity of Th cells is often accompanied, by default, by a Th2 phenotype [55, 180]. Another clinical feature common to patients from HIES and SCID/CID cohorts was neutropenia, which probably contributes to the wide spectrum of infections found in these patients [7-9, 170].…”

Section: Pgm3 Deficiencymentioning

confidence: 99%

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Human hyper-IgE syndrome: singular or plural?

et al. 2018

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Spectacular progress has been made in the characterization of human hyper-IgE syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency defined as an association of atopy in a context of very high serum IgE levels, characteristic bacterial and fungal diseases, low-level clinical and biological inflammation, and various non-hematopoietic developmental manifestations. Somewhat arbitrarily, three disorders were successively put forward as the underlying cause of HIES: autosomal dominant (AD) STAT3 deficiency, the only disorder corresponding to the original definition of HIES, and autosomal recessive (AR) DOCK8 and PGM3 deficiencies, in which atopy and high serum IgE levels occur in a context of manifestations not seen in patients with typical HIES. Indeed, these three disorders disrupt different molecular pathways, affect different cell types, and underlie different clinical phenotypes. Surprisingly, several other inherited inborn errors of immunity in which serum IgE levels are high, sometimes almost as high as those in HIES patients, are not considered to belong to the HIES group of diseases. Studies of HIES have been further complicated by the lack of a high serum IgE phenotype in all mouse models of the disease other than two Stat3 mutant strains. The study of infections in mutant mice has helped elucidate only some forms of HIES and infection. Mouse models of these conditions have also been used to study non-hematopoietic phenotypes for STAT3 deficiency, tissue-specific immunity for DOCK8 deficiency, and cell lineage maturation for PGM3 deficiency. We review here the history of the field of HIES since the first clinical description of this condition in 1966, together with the three disorders commonly referred to as HIES, focusing, in particular, on their mouse models. We propose the restriction of the term "HIES" to patients with an AD STAT3-deficiency phenotype, including the most recently described AR ZNF341 deficiency, thus excluding AR DOCK8 and PGM3 deficiencies from the definition of this disease.

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Section: Ige and Its Productionmentioning

confidence: 99%

Section: Ige and Its Productionmentioning

confidence: 99%

Section: Pgm3 Deficiencymentioning

confidence: 99%

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Human hyper-IgE syndrome: singular or plural?

et al. 2018

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“…The study of atopy and the observed changes in adaptive and effector immunologic mechanisms associated with allergic disease in humans are extraordinarily complex . The orchestrated response that has gone awry requires multiple steps involving innate and adaptive immune cells, myriad pathways, molecules, biochemicals, and cellular and physical processes.…”

Section: Introductionmentioning

confidence: 99%

“…The study of atopy and the observed changes in adaptive and effector immunologic mechanisms associated with allergic disease in humans are extraordinarily complex. [1][2][3][4] The orchestrated response that has gone awry requires multiple steps involving innate and adaptive immune cells, myriad pathways, molecules, biochemicals, and cellular and physical processes. Moreover, many of these entities may be substantially modified by environmental exposures or processes such that atopy, which describes the inborn propensity to develop allergies, may not always manifest as clinical allergic disease.…”

Section: Introductionmentioning

confidence: 99%

The clinical and mechanistic intersection of primary atopic disorders and inborn errors of growth and metabolism

Lyons

Milner

2018

Immunological Reviews

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Summary Dynamic changes in metabolism have long been understood as critical for both the initiation and maintenance of innate and adaptive immune responses. A number of recent advances have clarified details of how metabolic pathways can specifically affect cellular function in immune cells. Critical to this understanding is ongoing study of the congenital disorders of glycosylation and other genetic disorders of metabolism that lead to altered immune function in humans. While there are a number of immune phenotypes associated with metabolic derangements caused by single gene disorders, several genetic mutations have begun to link discrete alterations in metabolism and growth specifically with allergic disease. This subset of primary atopic disorders is of particular interest as they illuminate how hypomorphic mutations which allow for some residual function of mutated protein products permit the “abnormal” allergic response. This review will highlight how mutations altering sugar metabolism and mTOR activation place similar constraints on T lymphocyte metabolism to engender atopy, and how alterations in JAK/STAT signaling can impair growth and cellular metabolism while concomitantly promoting allergic diseases and reactions in humans.

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Antigens and Allergens

Klimov

2022

Textbook of Allergen Tolerance

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Primary atopic disorders

Abstract: Important insights from monogenic disorders into the immunopathogenesis of allergic diseases and reactions are discussed.

Cited by 77 publications

References 177 publications

Human hyper-IgE syndrome: singular or plural?

Human hyper-IgE syndrome: singular or plural?

The clinical and mechanistic intersection of primary atopic disorders and inborn errors of growth and metabolism

Antigens and Allergens

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