C. Thumerelle

Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

Whole-exome sequencing reveals activating STAT1 mutations in some patients with autosomal dominant chronic mucocutaneous candidiasis disease.

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

Background —STAT3 deficiency is responsible for autosomal dominant hyper-IgE syndrome characterized by recurrent bacterial and fungal infections, connective tissue abnormalities, hyper-IgE 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) for vascular abnormalities. They were explored with whole-body magnetic resonance imaging angiography, coronary multislice computed tomography and echo-tracking-based imaging of the carotid arteries. We also assayed for serum biomarkers of inflammation and endothelial dysfunction. Finally, murine models of aortic aneurysm were studied in the presence and absence of inhibitors of STAT3-dependent signaling. Brain abnormalities (white matter hyperintensities, lacunar lesions suggestive of ischemic infarcts, atrophy) were found in 95% of patients. Peripheral and brain artery abnormalities were reported in 84% of patients, whereas coronary artery abnormalities were detected in 50%. 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 STAT3-deficient patients. This feature is consistent with the greater susceptibility to vascular aneurysm observed after inhibition of STAT3-dependent signaling in mouse models.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 patients with STAT3 deficiency (median age, 26 years; range, 17 to 44) for vascular abnormalities. We explored the carotid arteries with whole-body magnetic resonance imaging angiography, coronary multislice computed tomography, and echo-tracking–based imaging. 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.

Asthma control assessment in a pediatric population: comparison between GINA/NAEPP guidelines, Childhood Asthma Control Test (C‐ACT), and physician's rating

Guidelines recommend regular assessment of asthma control. The Childhood Asthma Control Test (C‐ACT) is a clinically validated tool.

The lung is involved in juvenile dermatomyositis.

Juvenile dermatomyositis (JDM) is the main cause of chronic idiopathic inflammatory myopathy of autoimmune origin in children. The aim of this multicenter prospective study was to describe respiratory status and treatment of children followed for JDM.