Delayed development of a de novo contralateral middle cerebral artery aneurysm in a patient with hyperimmunoglobulin E syndrome: A case report

Nussbaum, Eric S.; Torok, Collin M.; Carroll, Jason J; Gunderman, Allicia M

doi:10.1177/1591019919828657

Cited by 4 publications

(6 citation statements)

References 25 publications

(42 reference statements)

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“…The TNF-α-induced STAT3 phosphorylation was prevented by the IL-6R antagonist, indicating that the effect is mediated by an autocrine signaling loop through TNF-α-induced secretion of IL-6 (Supplemental Figure 2A). Indeed, measurement of IL-6 in cell culture medium confirmed that both control and AD-HIES skin fibroblasts increased IL-6 secretion in response patients live long enough for nonimmune complications to become a major cause of death (10,16,17). In the current study, we investigate mechanisms underlying nonimmune abnormalities of AD-HIES in order to better understand the disease pathophysiology and find a promising target or targets for pharmacological therapy.…”

Section: Introductionmentioning

confidence: 87%

Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome

Dmitrieva

Walts

Nguyen

et al. 2020

Journal of Clinical Investigation

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Section: Introductionmentioning

confidence: 87%

Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome

Dmitrieva

Walts

Nguyen

et al. 2020

Journal of Clinical Investigation

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“…Cerebrovascular aneurysms may be silent or present symptomatically with rupture, causing significant mortality [ 91 ]. Management of asymptomatic aneurysms poses a dilemma, as intervention confers significant risk.…”

Section: Clinical Spectrum Of Stat3-hiesmentioning

confidence: 99%

STAT3 Hyper-IgE Syndrome—an Update and Unanswered Questions

2021

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The hyper-IgE syndromes (HIES) are a heterogeneous group of inborn errors of immunity sharing manifestations including increased infection susceptibility, eczema, and raised serum IgE. Since the prototypical HIES description 55 years ago, areas of significant progress have included description of key disease-causing genes and differentiation into clinically distinct entities. The first two patients reported had what is now understood to be HIES from dominant-negative mutations in signal transduction and activator of transcription 3 (STAT3-HIES), conferring a broad immune defect across both innate and acquired arms, as well as defects in skeletal, connective tissue, and vascular function, causing a clinical phenotype including eczema, staphylococcal and fungal skin and pulmonary infection, scoliosis and minimal trauma fractures, and vascular tortuosity and aneurysm. Due to the constitutionally expressed nature of STAT3, initial reports at treatment with allogeneic stem cell transplantation were not positive and treatment has hinged on aggressive antimicrobial prophylaxis and treatment to prevent the development of end-organ disease such as pneumatocele. Research into the pathophysiology of STAT3-HIES has driven understanding of the interface of several signaling pathways, including the JAK-STAT pathways, interleukins 6 and 17, and the role of Th17 lymphocytes, and has been expanded by identification of phenocopies such as mutations in IL6ST and ZNF341. In this review we summarize the published literature on STAT3-HIES, present the diverse clinical manifestations of this syndrome with current management strategies, and update on the uncertain role of stem cell transplantation for this disease. We outline key unanswered questions for further study.

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“…Medium size arterial abnormalities are most common, particularly affecting coronary and intracranial vasculature 95 . Cerebrovascular aneurysms can be silent or present symptomatically with rupture causing significant mortality 96 . The etiology of vasculopathy in HIES is not well understood and how vascular disease may be prevented in this patient population remains unknown.…”

Section: Stat3‐related Diseasementioning

confidence: 99%

“…Optimizing bone health and modifiable risk factors for coronary arterial disease, such as hypertension and hyperlipidemia are also recommended. Patients should undergo surveillance for arterial aneurysms every 3–5 years 96 . The role of HSCT for AD HIES remains uncertain.…”

Section: Stat3‐related Diseasementioning

confidence: 99%

“…95 Cerebrovascular aneurysms can be silent or present symptomatically with rupture causing significant mortality. 96 The etiology of vasculopathy in HIES is not well understood and how vascular disease may be prevented in this patient population remains unknown. Brain imaging reveals Chiari 1 malformation in approximately 20% of individuals and focal hyperintensities approximately 70% of individuals.…”

Section: Stat3 Loss Of Functionmentioning

confidence: 99%

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JAK/STAT defects and immune dysregulation, and guiding therapeutic choices

Chaimowitz,

Smith,

Forbes Satter

2024

Immunological Reviews

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SummaryInborn errors of immunity (IEIs) encompass a diverse spectrum of genetic disorders that disrupt the intricate mechanisms of the immune system, leading to a variety of clinical manifestations. Traditionally associated with an increased susceptibility to recurrent infections, IEIs have unveiled a broader clinical landscape, encompassing immune dysregulation disorders characterized by autoimmunity, severe allergy, lymphoproliferation, and even malignancy. This review delves into the intricate interplay between IEIs and the JAK–STAT signaling pathway, a critical regulator of immune homeostasis. Mutations within this pathway can lead to a wide array of clinical presentations, even within the same gene. This heterogeneity poses a significant challenge, necessitating individually tailored therapeutic approaches to effectively manage the diverse manifestations of these disorders. Additionally, JAK–STAT pathway defects can lead to simultaneous susceptibility to both infection and immune dysregulation. JAK inhibitors, with their ability to suppress JAK–STAT signaling, have emerged as powerful tools in controlling immune dysregulation. However, questions remain regarding the optimal selection and dosing regimens for each specific condition. Hematopoietic stem cell transplantation (HSCT) holds promise as a curative therapy for many JAK–STAT pathway disorders, but this procedure carries significant risks. The use of JAK inhibitors as a bridge to HSCT has been proposed as a potential strategy to mitigate these risks.

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Delayed development of a de novo contralateral middle cerebral artery aneurysm in a patient with hyperimmunoglobulin E syndrome: A case report

Cited by 4 publications

References 25 publications

Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome

Impaired angiogenesis and extracellular matrix metabolism in autosomal-dominant hyper-IgE syndrome

STAT3 Hyper-IgE Syndrome—an Update and Unanswered Questions

JAK/STAT defects and immune dysregulation, and guiding therapeutic choices

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