Cytokine secretion and NK cell activity in human ADAM17 deficiency.

Genetic deficiencies provide insights into gene function in humans. Here we describe a patient with a very rare genetic deficiency of ADAM17. We show that the patient's PBMCs had impaired cytokine secretion in response to LPS stimulation, correlating with the clinical picture of severe bacteremia from which the patient suffered. ADAM17 was shown to cleave CD16, a major NK killer receptor. Functional analysis of patient's NK cells demonstrated that his NK cells express normal levels of activating receptors and maintain high surface levels of CD16 following mAb stimulation. Activation of individual NK cell receptors showed that the patient's NK cells are more potent when activated directly by CD16, albeit no difference was observed in Antibody Depedent Cytotoxicity (ADCC) assays. Our data suggest that ADAM17 inhibitors currently considered for clinical use to boost CD16 activity should be cautiously applied, as they might have severe side effects resulting from impaired cytokine secretion.

Hospitalization of children with down syndrome.

INTRODUCTION: Children with Down syndrome present with multiple medical problems in a higher prevalence compared with the general population, which may lead to hospitalizations. METHODS: Analysis of 560 hospitalizations of 162 children aged 0-16 years with Down syndrome at Hadassah Medical Center during the years 1988-2007 compared with data on children in the general population, hospitalized at the same period. Data was collected from patient files and statistical data from the Ministry of Health. RESULTS: Respiratory infections were the leading cause for hospitalization of children with Down syndrome. The number of hospitalizations of children with Down syndrome compared to the number of all children, who were hospitalized was surprisingly similar to their proportion in the general population. Eleven children died during their hospitalization (five heart failure, three sepsis, one respiratory tract infection, and one due to complication after surgery). Nine of the 11 had a congenital heart anomaly. CONCLUSION: Children with Down syndrome can present with complex medical issues and we support the concept of a multidisciplinary team that has experience and knowledge to serve as a "one stop shop" for these individuals and their families, with timely visits in which a comprehensive evaluation is performed, problems attended to and prevention plans applied. In this way, we may prevent morbidity, hospitalizations, and mortality.

Morbidity and hospitalizations of adults with Down syndrome.

Over the last decade a significant increase in the life expectancy of people with Down syndrome (DS) has been observed, which has caused a higher incidence of morbidity as they age. However, there is a lack of literature regarding morbidity and hospitalization of adults with DS. Analysis of 297 hospitalizations of 120 adults with DS aged 18-73 years hospitalized at Hadassah Medical Centers during the years 1988-2007 compared with data of the general population, hospitalized at the same period. At the age range 18-66 years, mean number of hospitalizations was significantly higher than the general population (P = 0.000001) with hospitalization also significantly longer (P = 0.0009). Exceptionally long hospitalizations were seen at the departments of internal medicine, dermatology and intensive care units. There was no significant difference in mortality between DS and the general population (P = 0.221). More than a fourth of the hospitalizations were caused by infectious diseases, mostly respiratory infections. Hypothyroidism was more prevalent compared with the estimated number reported by the literature (30.8% vs. 15%). Convulsive disorder was prevalent as well (15.8%). However, the prevalence of congenital heart disease, dementia, osteoporosis and obesity was found less than expected. Adults with DS are hospitalized more than the general population and for longer duration. The results of this study emphasize the need for preventive community-based medicine, awareness of co-morbidities and possible deterioration and to prepare the medical staff for a complex course of illness, expecting longer hospitalizations, arising from the complexity of this population.