Biallelic mutations in IRF8 impair human NK cell maturation and function

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8–/–, but not Irf8+/–, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense

Migration to western industrialised countries and perinatal health: a systematic review

Influxes of migrant women of childbearing age to receiving countries have made their perinatal health status a key priority for many governments. The international research collaboration Reproductive Outcomes And Migration (ROAM) reviewed published studies to assess whether migrants in western industrialised countries have consistently poorer perinatal health than receiving-country women. A systematic review of literature from Medline, Health Star, Embase and PsychInfo from 1995 to 2008 included studies of migrant women/infants related to pregnancy or birth. Studies were excluded if there was no cross-border movement or comparison group or if the receiving country was not western and industrialised. Studies were assessed for quality, analysed descriptively and meta-analysed when possible. We identified 133 reports (>20,000,000 migrants), only 23 of which could be meta-analysed. Migrants were described primarily by geographic origin; other relevant aspects (e.g., time in country, language fluency) were rarely studied. Migrants' results for preterm birth, low birthweight and health-promoting behaviour were as good or better as those for receiving-country women in >or=50% of all studies. Meta-analyses found that Asian, North African and sub-Saharan African migrants were at greater risk of feto-infant mortality than 'majority' receiving populations, and Asian and sub-Saharan African migrants at greater risk of preterm birth. The migration literature is extensive, but the heterogeneity of the study designs and definitions of migrants limits the conclusions that can be drawn. Research that uses clear, specific migrant definitions, adjusts for relevant risk factors and includes other aspects of migrant experience is needed to confirm and understand these association