RESUMEN
Most humans harbor both CD177neg and CD177pos neutrophils but 1-10% of people are CD177null, placing them at risk for formation of anti-neutrophil antibodies that can cause transfusion-related acute lung injury and neonatal alloimmune neutropenia. By deep sequencing the CD177 locus, we catalogued CD177 single nucleotide variants and identified a novel stop codon in CD177null individuals arising from a single base substitution in exon 7. This is not a mutation in CD177 itself, rather the CD177null phenotype arises when exon 7 of CD177 is supplied entirely by the CD177 pseudogene (CD177P1), which appears to have resulted from allelic gene conversion. In CD177 expressing individuals the CD177 locus contains both CD177P1 and CD177 sequences. The proportion of CD177hi neutrophils in the blood is a heritable trait. Abundance of CD177hi neutrophils correlates with homozygosity for CD177 reference allele, while heterozygosity for ectopic CD177P1 gene conversion correlates with increased CD177neg neutrophils, in which both CD177P1 partially incorporated allele and paired intact CD177 allele are transcribed. Human neutrophil heterogeneity for CD177 expression arises by ectopic allelic conversion. Resolution of the genetic basis of CD177null phenotype identifies a method for screening for individuals at risk of CD177 isoimmunisation.
Asunto(s)
Isoantígenos/biosíntesis , Neutropenia/inmunología , Neutrófilos/inmunología , Seudogenes/genética , Receptores de Superficie Celular/biosíntesis , Anticuerpos Anticitoplasma de Neutrófilos/biosíntesis , Anticuerpos Anticitoplasma de Neutrófilos/inmunología , Transfusión de Sangre Autóloga/efectos adversos , Proteínas Ligadas a GPI/biosíntesis , Proteínas Ligadas a GPI/genética , Regulación de la Expresión Génica , Heterogeneidad Genética , Humanos , Isoantígenos/sangre , Isoantígenos/genética , Isoantígenos/inmunología , Neutropenia/patología , Neutrófilos/metabolismo , Polimorfismo de Nucleótido Simple , Seudogenes/inmunología , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/inmunología , Trombocitopenia Neonatal AloinmuneRESUMEN
Health Canada's Radiation Protection Bureau has identified trace quantities of (134)Cs and (137)Cs in commercially available green tea products of Japanese origin. Referenced to March 11, 2011, the activity ratio ((134)Cs/(137)Cs) has been determined to be 1:1, which supports an origin from the Fukushima Dai-ichi Nuclear Power Plant accident. The upper limits of typical tea beverage preparation conditions were applied to the most contaminated of these green tea samples to determine the proportion of radiocesium contamination that would be available for human consumption. The distribution of radiocesium among the components of the extraction experiments (water, residual tea solid, and filter media) was determined by both conventional and Compton-suppressed gamma spectroscopy. The latter aided tremendously in providing a more complete radiocesium distribution profile, particularly for the shorter-lived (134)Cs. Cesium extraction efficiencies of 64 ± 7% and 64 ± 5% were determined based on (134)Cs and (137)Cs, respectively. Annual, effective dose estimates from ingestion of (137)Cs and (134)Cs (1.8-3.7 µSv), arising from the consumption of tea beverages prepared from the most contaminated of these samples, are insignificant relative to both total (â¼ 2.4 mSv) and ingested (â¼ 0.28 mSv) annual effective doses received from naturally occurring radioactive sources. As such, there is no health concern arising from the consumption of green tea beverages contaminated with radiocesium at the levels encountered in this study.