Regulatory T cells expressing CD19-targeted chimeric antigen receptor restore homeostasis in Systemic Lupus Erythematosus.

Systemic Lupus Erythematosus (SLE) is a progressive disease leading to immune-mediated tissue damage, associated with an alteration of lymphoid organs. Therapeutic strategies involving regulatory T (Treg) lymphocytes, which physiologically quench autoimmunity and support long-term immune tolerance, are considered, as conventional treatment often fails. We describe here a therapeutic strategy based on Tregs overexpressing FoxP3 and harboring anti-CD19 CAR (Fox19CAR-Tregs). Fox19CAR-Tregs efficiently suppress proliferation and activity of B cells in vitro, which are relevant for SLE pathogenesis. In an humanized mouse model of SLE, a single infusion of Fox19CAR-Tregs restricts autoantibody generation, delay lymphopenia (a key feature of SLE) and restore the human immune system composition in lymphoid organs, without detectable toxicity. Although a short survival, SLE target organs appear to be protected. In summary, Fox19CAR-Tregs can break the vicious cycle leading to autoimmunity and persistent tissue damage, representing an efficacious and safe strategy allowing restoration of homeostasis in SLE.

[Severe forms of chikungunya virus infection in a pediatric intensive care unit on Reunion Island]. / Infections graves a virus chikungunya en réanimation pédiatrique a l'ile de La Réunion.

UNLABELLED: In 2005-2006, an unexpected, massive outbreak of chikungunya occurred on Reunion Island, a French overseas territory in the Indian Ocean. This arboviral infection transmitted by a mosquito of the Aedes genus is usually benign. A surprising feature of the Reunion Island epidemic was the occurrence of rare severe forms involving adults as well as children. OBJECTIVES: The purpose of this report is to describe severe forms of chikungunya observed in children hospitalized in a pediatric intensive care unit. PATIENTS AND METHODS: This retrospective single-center study was conducted from January 1st to April 30th, 2006. Children between 1 month and 15 years admitted to the pediatric intensive care unit with proven chikungunya infection were included. RESULTS: A total of 9 children were included. The main manifestations were extensive skin blisters in 5 cases, neurological symptoms (encephalopathy) in 4, cardiac complications (myocarditis, hemodynamic disorders) in 5 and bleeding in 1. Two children died. The causes of death were circulatory failure associated with coma and massive hemorrhage in one case and post-infectious encephalitis in the other. Three survivors present long-term neurologic or dermatologic sequels. DISCUSSION: Severe cases of chikungunya in children provide a stark reminder of the cardiac and neurological tropism of the virus and its hemorrhagic forms with high potential mortality and morbidity. These cases underline the need for personal protection measures and for research to develop specific antiviral therapy and vaccines to prevent potentially lethal forms of the disease.

[Fryns syndrome. Report on 3 new cases]. / Syndrome de Fryns. Présentation de 3 nouvelles observations.

BACKGROUND: Fryns syndrome is a lethal autosomal recessive syndrome which includes congenital diaphragmatic hernia (CDH), pulmonary hypoplasia, cranio-facial manifestations including a coarse face, a cleft palate / lip and cloudy corneae, distal limb hypoplasia and internal malformations including central nervous system, cardiovascular, gastrointestinal, urogenital and skeletal anomalies. CASES REPORT: We report on 3 patients with Fryns syndrome in the french Indian Ocean islands (La Réunion and Mayotte islands). Pregnancies were complicated by polyhydramnios. All patients had coarse face, cloudy corneae, cleft lip / palate or high-arched palate, hypoplastic nails and brachytelephalangy. They died in the neonatal period. Two had CDH and 1 did not have a diaphragmatic involvement but a severe respiratory distress syndrome with refractory hypoxemia. Cytogenetic studies of blood lymphocytes and skin fibroblasts were normal. CONCLUSIONS: Fryns syndrome is the most common multiple congenital anomaly associated with CDH. The diagnosis is strongly suggested when CHD and brachytelephalangy are associated. Phenotypes with CDH similar to Fryns syndrome have been described with cytogenetic aberrations with G-banded chromosome analysis and submicroscopic chromosome deletions detected by high resolution karyotyping or array comparative genomic hybridization (CGH). Exclusion of chromosome aberrations (including isochromosome 12p in skin fibroblasts) is needed prior to making the diagnosis of Fryns syndrome. In sporadic cases, high resolution karyotyping or array CGH should be performed for correct diagnosis and genetic counselling.

Fryns syndrome without diaphragmatic hernia. Report on a new case and review of the literature.

Fryns syndrome is an autosomal recessive multiple congenital anomaly syndrome characterized by coarse facies, diaphragmatic hernia, distal limb hypoplasia and malformations of the cardiovascular, gastrointestinal, genitourinary and central nervous systems. Diaphragmatic hernia is a leading diagnostic feature in Fryns syndrome, recorded in more than 80% of cases. We report a newborn with clinical features of Fryns syndrome except the diaphragmatic hernia. Cases of Fryns syndrome without diaphragmatic hernia are reviewed. Even in the absence of diaphragmatic hernia, pulmonary anomalies are described in Fryns syndrome, especially pulmonary hypoplasia. Fetal mice, exposed to nitrofen, have a high incidence of congenital diaphragmatic hernia and other malformations similar to that seen in Fryns syndrome. Nitrofen might target molecular mechanisms similar to those involved in Fryns syndrome.

[Bronchopulmonary dysplasia and cytomegalovirus pneumonia]. / Dysplasie bronchopulmonaire et pneumopathie à cytomégalovirus.

Hyaline membrane disease (HMD) of premature newborn can lead to bronchopulmonary dysplasia (BPD). We report the observation of a 33 weeks premature newborn with HMD, treated with exogenous surfactant and mechanical ventilation. The patient developed respiratory distress with oxygen dependency initially related to BPD. Because of worsening of respiratory condition after 2 months, despite corticosteroid therapy, further investigation was performed. Cytomegalovirus (CMV) was found in urine and in the pharynx and CMV-pneumonia was diagnosed. Treatment with gancyclovir allowed a rapid regression of symptoms. Association between BPD and CMV-pneumonia has been previously reported but the causal relationship is controversial. In premature newborn, CMV-pneumonia can appear clinically and radiologically like a BPD. When evolution is atypical, with persistence of respiratory distress despite BPD treatment, CMV-pneumonia must be considered as a specific antiviral therapy may be discussed.

[Neonatal accidental burn by isopropyl alcohol]. / Brûlure néonatale accidentelle à l'isopropanol.

Antiseptic solutions are commonly used for skin care but are not always safe. In preterm infants, application of antiseptic solutions can lead to serious burns. We report the case of a premature newborn who developed severe burns at 35 weeks post-conceptional age, after his mother used disposable antiseptic towels containing isopropyl alcohol for his skin care. Burns outcome led to diffuse skin burn and death of the baby. Several cases of isopropyl alcohol poisoning through skin absorption have been reported in neonate and infants. Because of its neonatal toxicity, isopropyl alcohol has been excluded from composition of antiseptic solutions commonly used in neonatology. However, isopropyl alcohol is still available in many housecleaning and cosmetic products, while its toxic effects in children are not clearly mentioned. A specific mention "toxic for infants and children" should appear on mass consumption products containing isopropyl alcohol. Moreover, health workers may individually inform parents about possible hazards of poisoning through skin absorption.

[Malignant pertussis in the young infant]. / La coqueluche maligne du petit nourrisson.

UNLABELLED: Pertussis remains in France the first cause of bacterial, infectious death in infant aged 10 days to 2 months. It is especially in this age group that malignant pertussis occurs. CASE REPORT: A 40-day-old infant was admitted in the intensive care unit with symptoms of bronchiolitis along with a 200 bpm permanent tachycardia. He presented a marked leukocytosis with lymphocytosis. On the second day, convulsions and coma occurred, followed rapidly by respiratory failure, with a subsequent deterioration due to the development of severe pulmonary hypertension. Circulatory failure caused the infant's death on the beginning of the 5th day. Pertussis was confirmed by PCR on nasopharyngeal swab. Intra-familial contamination was most likely. COMMENTS: Malignant pertussis is characterized by the very young age of patients, permanent tachycardia sine materia, dyspnea with early respiratory failure, frequent neurological symptoms, severe hyperleukocytosis and hyperlymphocytosis, and deep hyponatremia with oliguria and edema. Mortality remains superior to 75% despite the various treatments and life support measures that have been attempted. Adult pertussis, which represents one third of the cases of prolonged cough in this age group, is the main source of contamination of non-immunized young infants. This mode of transmission stresses the importance of the generalization of pertussis vaccine booster in early adolescence, which is recommended in France since 1998. Its extension towards the adult age is under study.