ABSTRACT
Severe influenza disease strikes otherwise healthy children and remains unexplained. We report compound heterozygous null mutations in IRF7, which encodes the transcription factor interferon regulatory factor 7, in an otherwise healthy child who suffered life-threatening influenza during primary infection. In response to influenza virus, the patient's leukocytes and plasmacytoid dendritic cells produced very little type I and III interferons (IFNs). Moreover, the patient's dermal fibroblasts and induced pluripotent stem cell (iPSC)-derived pulmonary epithelial cells produced reduced amounts of type I IFN and displayed increased influenza virus replication. These findings suggest that IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans. They also show that severe influenza may result from single-gene inborn errors of immunity.
Subject(s)
Heterozygote , Influenza A Virus, H1N1 Subtype , Influenza, Human/immunology , Interferon Regulatory Factor-7/genetics , Interferon Type I/biosynthesis , Respiratory Distress Syndrome/immunology , Child , Dendritic Cells/immunology , Female , Fibroblasts/immunology , Genes, Recessive , Humans , Induced Pluripotent Stem Cells/immunology , Influenza, Human/complications , Influenza, Human/genetics , Interferon Type I/genetics , Leukocytes/immunology , Lung/immunology , Mutation , Respiratory Distress Syndrome/genetics , Respiratory Distress Syndrome/virology , Respiratory Mucosa/immunologyABSTRACT
PURPOSE: The main treatment for majority of pediatric brain tumors relies on surgery. In postoperative period, patients require monitoring in a pediatric intensive care unit (PICU). In this study, we analyzed the incidence of postoperative neurological complications and the outcome of neurological impairment in individual patients. PATIENTS AND METHODS: Our retrospective single-center study concerned all patients who were admitted to the PICU of the University Hospital of Angers between 2002 and 2008, after brain tumor resection. Population, perioperative data, and outcome through the stay in PICU have been analyzed. RESULTS: We reported 117 neurosurgical procedures. Majority of children (85.3%) were affected by neurological deficit before surgery: cranial nerve palsy and cerebellar syndrome were the most frequent impairment. In the first 2 days, neurological symptoms improved for 27 patients (23.7%), especially in children with preoperative cerebellar syndrome, convulsions, or endocrine disorders. Mean length of stay in PICU was correlated with the severity of neurological impairment (p = 0.006). Five children presented a transient mutism after surgery for infratentorial tumors (n = 5/54, 9.2%). Eight spontaneous cerebral spinal fluid leaks occurred precociously after surgery, and neurological infections complicated half of them. Neurological infections occurred in 12 patients (ten meningitis, one ventriculitis, and one brain abscess). One patient died after surgery. CONCLUSIONS: All these complications and their risk factors have to be systematically searched for in order to decrease postoperative morbidity of brain tumors in children. They justify neurosurgeons and anesthesiologists specialized in these pathologies.
