The Reliable, Automatic Classification of Neonates in First-Tier MALDI-MS Screening for Sickle Cell Disease.

Previous research has shown that a MALDI-MS technique can be used to screen for sickle cell disease (SCD), and that a system combining automated sample preparation, MALDI-MS analysis and classification software is a relevant approach for first-line, high-throughput SCD screening. In order to achieve a high-throughput "plug and play" approach while detecting "non-standard" profiles that might prompt the misclassification of a sample, we have incorporated various sets of alerts into the decision support software. These included "biological alert" indicators of a newborn's clinical status (e.

A Multicentre Pilot Study of a Two-Tier Newborn Sickle Cell Disease Screening Procedure with a First Tier Based on a Fully Automated MALDI-TOF MS Platform.

The reference methods used for sickle cell disease (SCD) screening usually include two analytical steps: a first tier for differentiating haemoglobin S (HbS) heterozygotes, HbS homozygotes and β-thalassemia from other samples, and a confirmatory second tier. Here, we evaluated a first-tier approach based on a fully automated matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) platform with automated sample processing, a laboratory information management system and NeoSickle software for automatic data interpretation. A total of 6701 samples (with high proportions of phenotypes homozygous (FS) or heterozygous (FAS) for the inherited genes for sickle haemoglobin and samples from premature newborns) were screened.

Newborn screening for sickle cell disease in Europe: recommendations from a Pan-European Consensus Conference.

Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe.

Use of dried blood spots and inductively coupled plasma mass spectrometry for multi-element determination in blood.

The paper describes the development of an inductively coupled plasma mass spectrometry (ICP MS) method for multitrace element determination in dried blood spots (DBSs). The analytical conditions were optimized using Seronorm™ L-3 and L-1 Certified Reference Materials. The best results were obtained by sampling blood drops on a decontaminated PVDF filter membrane.

MALDI-TOF MS profiling as the first-tier screen for sickle cell disease in neonates: matching throughput to objectives.

Purpose: Universal newborn screening for sickle cell diseases (SCDs) is not currently performed in many countries concerned by this public health problem. Owing to the technical and financial limitations of standard profiling methods (IEF coupled to subsequent HPLC), ethnically targeted neonatal screening is often preferred. Here, we demonstrate that MALDI-MS-based SCD newborn screening could be considered as a potential method for a strategy to universal screening because of its high throughput, cost-effectiveness, sensitivity and ability to automatically discriminate sickle haemoglobin.

Potential of the Sebia Capillarys neonat fast automated system for neonatal screening of sickle cell disease.

Background: Most screening programs for sickle cell disease (SCD) utilize isoelectric focusing (IEF) or high performance liquid chromatography (HPLC) to detect haemoglobin (Hb) variants. The first method is not automated and becomes too tedious when many samples have to be investigated. The aim of this work is to explore the capacity of an automated capillary electrophoresis (CE) system, with full traceability, as a tool for newborn screening of SCD.

Combining immunoreactive trypsinogen and pancreatitis-associated protein assays, a method of newborn screening for cystic fibrosis that avoids DNA analysis.

Objectives: To evaluate the performance of a strategy in which, after immunoreactive trypsinogen (IRT) determination, genetic analysis is replaced by a biological test, the pancreatitis-associated protein (PAP) enzyme-linked immunosorbent assay (ELISA).

Study Design: The French newborn screening program includes cystic fibrosis (CF) screening by the IRT/CFTR mutation strategy. PAP was assayed on screening cards, in parallel with IRT, in all newborns from 5 French regions (n = 204,749).

Tumor necrosis factor alpha increases the expression of glycosyltransferases and sulfotransferases responsible for the biosynthesis of sialylated and/or sulfated Lewis x epitopes in the human bronchial mucosa.

There is increasing evidence that inflammation may affect glycosylation and sulfation of various glycoproteins. The present study reports the effect of tumor necrosis factor alpha (TNF-alpha), a proinflammatory cytokine, on the glycosyl- and sulfotransferases of the human bronchial mucosa responsible for the biosynthesis of Lewis x epitope and of its sialylated and/or sulfated derivatives, which are expressed in human bronchial mucins. Fragments of macroscopically normal human bronchial mucosa were exposed to TNF-alpha at a concentration of 20 ng/ml.