Hyperimmunoglobulinemia E syndrome associated with coronary artery aneurysms: deficiency of central memory CD4+ T cells and expansion of effector memory CD4+ T cells

Young, T; Jerome, D.; Gupta, Sudhir

doi:10.1016/s1081-1206(10)60887-3

Cited by 24 publications

(24 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coronary artery abnormalities (notably aneurysms) have been previously reported in patients with AD-HIES, including a recently studied group of 26 STAT3-deficient subjects. 9,10,12,13 Cerebral vascular events (stroke, retinal occlusion, and internal carotid aneurysm) were first reported in 3 patients with AD-HIES, 1 and 5 other cases with lacunar infarction were subsequently identified. 8 In the present cohort (in which all the patients had genetically confirmed STAT3 deficiency), it is noteworthy that all anatomic areas appear to be potentially affected, with a trend toward more damage in small-and medium-diameter vessels.…”

Section: Chandesris Et Al Vascular Abnormalities In Human Stat3 Deficmentioning

confidence: 99%

Frequent and Widespread Vascular Abnormalities in Human Signal Transducer and Activator of Transcription 3 Deficiency

Chandesris

Azarine

Ong

et al. 2012

Circ Cardiovasc Genet

View full text Add to dashboard Cite

Background-Signal transducer and activator of transcription 3 (STAT3) deficiency is responsible for autosomal dominant hyperimmunoglobulin E syndrome, characterized by recurrent bacterial and fungal infections, connective tissue abnormalities, hyperimmunoglobulin E, and Th17 lymphopenia. Although vascular abnormalities have been reported in some patients, the prevalence, characteristics, and etiology of these features have yet to be described. Methods and Results-We prospectively screened 21 adult STAT3-deficient patients (median age: 26 years; range 17-44 years) for vascular abnormalities. We explored the entire arterial vasculature with whole-body magnetic resonance imaging angiography, coronary multislice computed tomography, and echo-tracking-based imaging specifically for the carotid arteries. We also assayed for serum biomarkers of inflammation and endothelial dysfunction. Finally, we studied murine models of aortic aneurysm in the presence and absence of inhibitors of STAT3-dependent signaling. Ninety-five percent of patients showed brain abnormalities (white matter hyperintensities, lacunar lesions suggestive of ischemic infarcts, and atrophy). We reported peripheral and brain artery abnormalities in 84% of the patients and detected coronary artery abnormalities in 50% of the patients. The most frequent vascular abnormalities were ectasia and aneurysm. The carotid intima-media thickness was markedly decreased, with a substantial increase in circumferential wall stress, indicating the occurrence of hypotrophic arterial remodeling in this STAT3-deficient population. Systemic inflammatory biomarker levels correlated poorly with the vascular phenotype. In vivo inhibition of STAT3 signaling or blockade of IL-17A resulted in a marked increase in aneurysm severity and fatal rupture in mouse models. Conclusions-Vascular abnormalities are highly prevalent in patients with STAT3 deficiency. This feature is consistent with the greater susceptibility to vascular aneurysm observed after inhibition of STAT3-dependent signaling in mouse models. (Circ Cardiovasc Genet. 2012;5:25-34.)

show abstract

Section: Chandesris Et Al Vascular Abnormalities In Human Stat3 Deficmentioning

confidence: 99%

Frequent and Widespread Vascular Abnormalities in Human Signal Transducer and Activator of Transcription 3 Deficiency

Chandesris

Azarine

Ong

et al. 2012

Circ Cardiovasc Genet

View full text Add to dashboard Cite

show abstract

“…Vascular abnormalities are common in HIES (21–23). One man suffered a myocardial infarction due to a large left anterior descending coronary artery aneurysm (22).…”

Section: Clinical Manifestations (Table 1)mentioning

confidence: 99%

“…Leukocytosis and acute phase reactants, such as C-reactive protein during infection, may not be as high as expected. Lymphocyte phenotyping shows decreased memory T cells, and antibody responses are variable (3, 23, 27). …”

Section: Clinical Manifestations (Table 1)mentioning

confidence: 99%

Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes

2009

View full text Add to dashboard Cite

ABSTRACT:Autosomal dominant Hyper-IgE syndrome (AD-HIES) is a rare primary immunodeficiency characterized by eczema, recurrent skin and lung infections, elevated serum IgE, and various connective tissue, skeletal, and vascular abnormalities. Mutations in signal transducer and activator of transcription 3 (STAT3) have recently been found to account for most cases; however, the pathogenesis of the varied features remains poorly defined. A distinct syndrome, known as autosomal recessive HIES (AR-HIES) manifests as severe eczema, recurrent bacterial and viral skin infections, and sinopulmonary infections. As opposed to STAT3 deficient HIES, AR-HIES lacks the connective tissue and skeletal manifestations but has an increase in neurologic abnormalities. In this review, we discuss the clinical presentations, genetic etiologies, and immunologic abnormalities of these two syndromes. In addition, we discuss animal models of STAT3 deficiency that provide insight into the pathogenesis of HIES. Further understanding of how STAT3 results in the diverse manifestations of HIES will allow us to develop more specific therapies for HIES as well as for many of the manifestations, such as scoliosis, recurrent staphylococcal infections, and eczema, which are common in the general population. (Pediatr Res 65: 32R-37R, 2009)

show abstract

“…Minimal trauma fractures occur as well as osteoporosis, although these two findings appear to be independent of each other. Vascular abnormalities, including intracranial aneurysms and coronary artery ectasia, tortuosity, and aneurysms are common [15,16]. Asymptomatic cerebral T2-weighted hyperintensities, increased prevalence of lacunar infarcts, and increased Arnold Chiari 1 malformations are seen on the brain MRIs of many patients [17][18][19].…”

Section: Autosomal Dominant and Sporadic Stat3 Deficiencymentioning

confidence: 99%

Pathogenesis of Hyper IgE Syndrome

Heimall

Freeman

Holland

2009

Clinic Rev Allerg Immunol

View full text Add to dashboard Cite

Hyper IgE syndrome (HIES) is a rare primary immunodeficiency characterized by the triad of elevated IgE and eosinophilia, eczema, and recurrent skin and pulmonary infections. The autosomal dominant (AD) form of HIES results from mutations in STAT3 and is characterized by disordered inflammation, connective tissue, and skeletal abnormalities. Tissue-specific STAT3 deficiency in animals, cytokine and transcriptional array data, and careful clinical phenotyping have explained some of the pathophysiology of the immunologic and non-immunologic abnormalities of AD-HIES. In depth study of the role of STAT3 mutations in specific aspects of HIES may lead to better understanding and new approaches to treatment of conditions intrinsic to HIES that are common in the general population, such as staphylococcal infections, scoliosis, osteoporosis, bronchiectasis, and arterial aneurysms. As the genotypes of STAT3 deficiency are further characterized, genotype-phenotype correlations may emerge that will be informative regarding specific molecular interactions. Autosomal recessive forms of hyper IgE (AR-HIES) have also been reported. A single case of homozygous deficiency of the signal protein Tyk2 has been reported as well as a recessive syndrome with some features overlapping AD-HIES, but for which the genetic etiology is unknown. Better understanding of the pathophysiology and mechanisms of dominant and recessive hyper IgE syndromes will shed light on somatic and immune biology and may improve quality of life and survival for HIES patients.

show abstract

Hyperimmunoglobulinemia E syndrome associated with coronary artery aneurysms: deficiency of central memory CD4+ T cells and expansion of effector memory CD4+ T cells

Cited by 24 publications

References 19 publications

Frequent and Widespread Vascular Abnormalities in Human Signal Transducer and Activator of Transcription 3 Deficiency

Frequent and Widespread Vascular Abnormalities in Human Signal Transducer and Activator of Transcription 3 Deficiency

Clinical Manifestations, Etiology, and Pathogenesis of the Hyper-IgE Syndromes

Pathogenesis of Hyper IgE Syndrome

Contact Info

Product

Resources

About