RESUMEN
Pollen from Salsola kali, i.e., saltwort, Russian thistle, is a major allergen source in the coastal regions of southern Europe, in Turkey, Central Asia, and Iran. S. kali-allergic patients mainly suffer from hay-fever (i.e., rhinitis and conjunctivitis), asthma, and allergic skin symptoms. The aim of this study was to investigate the importance of individual S. kali allergen molecules. Sal k 1, Sal k 2, Sal k 3, Sal k 4, Sal k 5, and Sal k 6 were expressed in Escherichia coli as recombinant proteins containing a C-terminal hexahistidine tag and purified by nickel affinity chromatography. The purity of the recombinant allergens was analyzed by SDS-PAGE. Their molecular weight was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and their fold and secondary structure were studied by circular dichroism (CD) spectroscopy. Sera from clinically well-characterized S. kali-allergic patients were used for IgE reactivity and basophil activation experiments. S. kali allergen-specific IgE levels and IgE levels specific for the highly IgE cross-reactive profilin and the calcium-binding allergen from timothy grass pollen, Phl p 12 and Phl p 7, respectively, were measured by ImmunoCAP. The allergenic activity of natural S. kali pollen allergens was studied in basophil activation experiments. Recombinant S. kali allergens were folded when studied by CD analysis. The sum of recombinant allergen-specific IgE levels and allergen-extract-specific IgE levels was highly correlated. Sal k 1 and profilin, reactive with IgE from 64% and 49% of patients, respectively, were the most important allergens, whereas the other S. kali allergens were less frequently recognized. Specific IgE levels were highest for profilin. Of note, 37% of patients who were negative for Sal k 1 showed IgE reactivity to Phl p 12, emphasizing the importance of the ubiquitous cytoskeletal actin-binding protein, profilin, for the diagnosis of IgE sensitization in S. kali-allergic patients. rPhl p 12 and rSal k 4 showed equivalent IgE reactivity, and the clinical importance of profilin was underlined by the fact that profilin-monosensitized patients suffered from symptoms of respiratory allergy to saltwort. Accordingly, profilin should be included in the panel of allergen molecules for diagnosis and in molecular allergy vaccines for the treatment and prevention of S. kali allergy.
Asunto(s)
Alérgenos , Reacciones Cruzadas , Inmunoglobulina E , Polen , Profilinas , Salsola , Humanos , Profilinas/inmunología , Profilinas/química , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Alérgenos/genética , Salsola/inmunología , Femenino , Polen/inmunología , Masculino , Reacciones Cruzadas/inmunología , Adulto , Proteínas Recombinantes/inmunología , Rinitis Alérgica Estacional/inmunología , Persona de Mediana Edad , Basófilos/inmunología , Basófilos/metabolismo , Antígenos de Plantas/inmunología , Antígenos de Plantas/genética , Adulto Joven , Adolescente , Proteínas de Plantas/inmunología , Proteínas de Plantas/genéticaRESUMEN
Preeclampsia, which affects approximately 5% of pregnancies, is a leading cause of maternal and perinatal death. The causes of preeclampsia remain unclear, but there is evidence for inherited susceptibility. Genome-wide association studies (GWAS) have not identified maternal sequence variants of genome-wide significance that replicate in independent data sets. We report the first GWAS of offspring from preeclamptic pregnancies and discovery of the first genome-wide significant susceptibility locus (rs4769613; P = 5.4 × 10-11) in 4,380 cases and 310,238 controls. This locus is near the FLT1 gene encoding Fms-like tyrosine kinase 1, providing biological support, as a placental isoform of this protein (sFlt-1) is implicated in the pathology of preeclampsia. The association was strongest in offspring from pregnancies in which preeclampsia developed during late gestation and offspring birth weights exceeded the tenth centile. An additional nearby variant, rs12050029, associated with preeclampsia independently of rs4769613. The newly discovered locus may enhance understanding of the pathophysiology of preeclampsia and its subtypes.
Asunto(s)
Feto , Predisposición Genética a la Enfermedad , Preeclampsia/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Genoma Humano , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Polimorfismo de Nucleótido Simple , Embarazo , Proteínas Gestacionales/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangreRESUMEN
Pre-eclampsia is a major cause of maternal and fetal mortality in pregnancy. The identification of genetic variants which predispose to pre-eclampsia demands large DNA collections from affected mothers and babies and controls, with reliable supporting phenotypic data. The InterPregGen study has assembled a consortium of researchers from Europe, Central Asia and South America with the aim of elucidating the genetic architecture of pre-eclampsia. The MoBa collection is playing a vital role in this collaborative venture, which has the potential to provide new insights into the causes of pre-eclampsia, and provide a rational basis for novel approaches to prevention and treatment.
