Proteome analysis of human neutrophil granulocytes from patients with monogenic disease using data-independent acquisition

Neutrophil granulocytes are critical mediators of innate immunity and tissue regeneration. Rare diseases of neutrophil granulocytes may affect their differentiation and/or functions. However, there are very few validated diagnostic tests assessing the functions of neutrophil granulocytes in these diseases. Here, we set out to probe omics analysis as a novel diagnostic platform for patients with defective differentiation and function of neutrophil granulocytes. We analyzed highly purified neutrophil granulocytes from 68 healthy individuals and 16 patients with rare monogenic diseases. Cells were isolated from fresh venous blood (purity >99%) and used to create a spectral library covering almost 8000 proteins using strong cation exchange fractionation. Patient neutrophil samples were then analyzed by data-independent acquisition proteomics, quantifying 4154 proteins in each sample. Neutrophils with mutations in the neutrophil elastase gene ELANE showed large proteome changes that suggest these mutations may affect maturation of neutrophil granulocytes and initiate misfolded protein response and cellular stress mechanisms. In contrast, only few proteins changed in patients with leukocyte adhesion deficiency (LAD) and chronic granulomatous disease (CGD). Strikingly, neutrophil transcriptome analysis showed no correlation with its proteome. In case of two patients with undetermined genetic causes, proteome analysis guided the targeted genetic diagnostics and uncovered the underlying genomic mutations. Data-independent acquisition proteomics may help to define novel pathomechanisms in neutrophil diseases and provide a clinically useful diagnostic dimension

Kedi tırmığı hastalığı

La multinacional IMPRESOR, es una compañía dedicada a la fabricación de impresoras y cartuchos de tinta, manejando la modalidad de comodato para la mayoria de sus clientes. Con la crisis de los los EEUU en 2007, IMPRESOR se vio obligada a tomar acciones para reducir costos de produccion, inicialmente la fabricación de los consumibles (cartuchos), y de las impresoras se realizaba en Canada, con estandares altos de calidad y costos de producción razonables. Para sobrellevar la crisis y generar ganancias que sostuvieran la operación Impresor decide abrir una nueva planta en Panama ya que este País ofrecia excelentes condiciones tributarias, ademas del bajo costo de la mano de obra. La nueva planta recibia continuas visitas de un ente regulador para poder contar un un sello de calidad. En una de las visitas se evidenciaron fallas en los procesos de producción, generando una no conformidad, por tal razon se solicito una revisión detallada de todos los procesos y se generaron planes de acción para corregirlos. Este hecho fue acompañado de unas directrices del ente regulador que obligaba a Impresor a buscar a cada uno de sus clientes y entregarles un documento en el cual se explicaban las fallas que se podian presentar con sus productos, Esta situación genero deconfianza en la mayoria de los cliente

Growth retardation in children with IgA deficiency

We evaluated the clinical and immunological manifestations of 14 children with IgA deficiency. Four of the patients were asymptomatic, and ten were symptomatic, with recurrent sino-pulmonary infections, allergic disease, recurrent intestinal giardiasis or celiac disease. Growth retardation was the second important feature in our patients. One of the seven patients with growth retardation had partial growth hormone deficiency. The levels of serum IgG and IgM were high in five and three patients, respectively. Cellular immunity was normal