scholarly journals Study Design for an Evaluation of Newborn Screening for SCID in the UK

2022 ◽  
Vol 8 (1) ◽  
pp. 4
Author(s):  
David Elliman
Keyword(s):  
False Positive ◽  
Screening Programme ◽  
Severe Combined Immunodeficiency ◽  
Cost Effective ◽  
Cell Receptor ◽  
Premature Babies ◽  
Separate Pathway ◽  
Excision Circles ◽  
Newborn Bloodspot Screening ◽  
The Uk

Severe combined immunodeficiency is a rare inherited disorder, which, if untreated, invariably proves fatal in late infancy or early childhood. With treatment, the prognosis is much improved. Early treatment of the siblings of cases, before they become symptomatic, has shown considerable improvements in outcomes. Based on this and the development of a test that can be used on the whole population of neonates (measurement of T-cell receptor excision circles—TRECs), many countries have added it to their routine newborn bloodspot screening programmes. The UK National Screening Committee (UKNSC) has considered whether SCID should be added to the UK screening programme and concluded that it was likely to be cost effective, but that there were a number of uncertainties that should be resolved before a national roll-out could be recommended. These include some aspects of the test, such as: cost; the use of different assays and cut-off levels to reduce false positive rates, while maintaining sensitivity; the overall benefits of screening for disease outcome in patients with SCID and other identified disorders; the need for a separate pathway for premature babies; the acceptability of the screening programme to parents of babies who have normal and abnormal (both true and false positive) screening results. To achieve this, screening of two thirds of babies born in England over a two-year period has been planned, beginning in September 2021. The outcomes and costs of care of babies identified by the screening will be compared with those of babies identified with SCID in the rest of the UK. The effect of the screening programme on parents will form part of a separate research project.

Immunodeficiency and Immunomonitoring

2015 ◽  
Vol 38 (1) ◽  
Author(s):  
Harald Renz
Keyword(s):  
Reference Values ◽  
Inflammatory Diseases ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Chronic Inflammatory Disease ◽  
Age Related ◽  
First Results ◽  
The Usa ◽  
Developing Area ◽  
Excision Circles

AbstractImmunological diagnostics is a rapidly developing area in laboratory medicine. Most recently, major developments in the area of immunodeficiency and the monitoring of chronic inflammatory diseases have been observed. Regarding immuno-monitoring, recently a consensus panel for basic flow cytometry has been published together with age-related reference values. In the USA, the search for severe inherited immunodeficiency diseases (such as severe combined immunodeficiency disease, SCID) is part of neonatal screening procedures. Recently, several US states published first results which are based on the measurement of T-cell receptor excision circles (TRECs). Furthermore, age-dependent reference values for the measurement of IgG subclasses and subclass-specific vaccination antibodies have been published. Monitoring of chronic inflammatory disease focuses on asthma. A novel classification based on the cellular distribution of neutrophils versus eosinophils in induced sputum has been developed. Furthermore, novel biomarkers, such as periostin, are currently under evaluation. Such novel approaches of phenotyping are now the basis of individualized therapeutic approaches in patients with (severe) asthma, who respond to certain biologicals.

scholarly journals A Cost-Effectiveness Analysis of Newborn Screening for Severe Combined Immunodeficiency in the UK

2019 ◽  
Vol 5 (3) ◽  
pp. 28 ◽  
Author(s):  
Alice Bessey ◽  
James Chilcott ◽  
Joanna Leaviss ◽  
Carmen de la Cruz ◽  
Ruth Wong
Keyword(s):  
Cost Effectiveness ◽  
Severe Combined Immunodeficiency ◽  
Cost Effective ◽  
Sensitivity Analyses ◽  
Combined Immunodeficiency ◽  
Tree Model ◽  
Life Years ◽  
The Uk ◽  
The Cost ◽  
The Impact

Severe combined immunodeficiency (SCID) can be detected through newborn bloodspot screening. In the UK, the National Screening Committee (NSC) requires screening programmes to be cost-effective at standard UK thresholds. To assess the cost-effectiveness of SCID screening for the NSC, a decision-tree model with lifetable estimates of outcomes was built. Model structure and parameterisation were informed by systematic review and expert clinical judgment. A public service perspective was used and lifetime costs and quality-adjusted life years (QALYs) were discounted at 3.5%. Probabilistic, one-way sensitivity analyses and an exploratory disbenefit analysis for the identification of non-SCID patients were conducted. Screening for SCID was estimated to result in an incremental cost-effectiveness ratio (ICER) of £18,222 with a reduction in SCID mortality from 8.1 (5–12) to 1.7 (0.6–4.0) cases per year of screening. Results were sensitive to a number of parameters, including the cost of the screening test, the incidence of SCID and the disbenefit to the healthy at birth and false-positive cases. Screening for SCID is likely to be cost-effective at £20,000 per QALY, key uncertainties relate to the impact on false positives and the impact on the identification of children with non-SCID T Cell lymphopenia.

scholarly journals Neonatal screening for severe primary immunodeficiency diseases using high-throughput triplex real-time PCR

Blood ◽  
2012 ◽  
Vol 119 (11) ◽  
pp. 2552-2555 ◽  
Author(s):  
Stephan Borte ◽  
Ulrika von Döbeln ◽  
Anders Fasth ◽  
Ning Wang ◽  
Magdalena Janzi ◽  
...  
Keyword(s):  
Newborn Screening ◽  
Ataxia Telangiectasia ◽  
Neonatal Screening ◽  
Severe Combined Immunodeficiency ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Nijmegen Breakage Syndrome ◽  
Inborn Errors ◽  
Guthrie Card ◽  
Excision Circles

Abstract Severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) are inborn errors of immune function that require prompt diagnosis and treatment to prevent life-threatening infections. The lack of functional T or B lymphocytes in these diseases serves as a diagnostic criterion and can be applied to neonatal screening. A robust triplex PCR method for quantitation of T-cell receptor excision circles (TRECs) and κ-deleting recombination excision circles (KRECs), using a single Guthrie card punch, was developed and validated in a cohort of 2560 anonymized newborn screening cards and in 49 original stored Guthrie cards from patients diagnosed with SCID, XLA, ataxia-telangiectasia, Nijmegen-breakage-syndrome, common variable immunodeficiency, immunoglobulin A deficiency, or X-linked hyper-IgMsyndrome. Simultaneous measurement of TREC and KREC copy numbers in Guthrie card samples readily identified patients with SCID, XLA, ataxia-telangiectasia and Nijmegen-breakage-syndrome and thus facilitates effective newborn screening for severe immunodeficiency syndromes characterized by the absence of T or B cells.

scholarly journals Toward the Analysis of Lymphocyte Development in Space: PCR-Based Amplification of T-Cell Receptor Excision Circles (TRECs) Aboard the International Space Station

2021 ◽  
Vol 9 (1) ◽  
pp. 159-163
Author(s):  
Elizabeth Reizis ◽  
Diana Cai ◽  
Lee Serpas ◽  
Emily J. Gleason ◽  
Kathryn Martin ◽  
...  
Keyword(s):  
T Cell ◽  
International Space Station ◽  
Space Station ◽  
Cost Effective ◽  
Cell Receptor ◽  
International Space ◽  
Immunodeficient Mice ◽  
Excision Circles ◽  
Human Exploration ◽  
Cancerous Cells

Abstract Spaceflight offers vast possibilities for expanding human exploration, whereas it also bears unique health risks. One of these risks is immune dysfunction, which can result in the reactivation of latent pathogens and increased susceptibility to infections. The ability to monitor the function of the immune system is critical for planning successful long-term space travel. T lymphocytes are immune cells that develop in the thymus and circulate in the blood. They can detect foreign, infected, or cancerous cells through T cell receptors (TCRs). The assembly of TCR gene segments, to produce functional TCR genes, can be monitored by measuring the presence of TCR excision circles (TRECs), circular fragments of DNA that are by-products of this assembly process mediated by the V(D)J recombination machinery. In this study, we used polymerase chain reaction (PCR) on the International Space Station (ISS) to detect TRECs in murine peripheral blood. We were able to detect TRECs in the blood of normal healthy mice of different ages, with an efficiency comparable to that achieved in ground controls. As expected, we were unable to detect TRECs in the blood of immunodeficient mice. These results are the first step in optimizing a specific, rapid, safe, and cost-effective PCR-based assay to measure the integrity of mammalian immune systems during spaceflight.

scholarly journals The Cost-Effectiveness of Expanding the UK Newborn Bloodspot Screening Programme to Include Five Additional Inborn Errors of Metabolism

2020 ◽  
Vol 6 (4) ◽  
pp. 93
Author(s):  
Alice Bessey ◽  
James Chilcott ◽  
Abdullah Pandor ◽  
Suzy Paisley
Keyword(s):  
Cost Effectiveness ◽  
Social Services ◽  
Inborn Errors Of Metabolism ◽  
Screening Programme ◽  
Tree Model ◽  
Inborn Errors ◽  
Life Years ◽  
Newborn Bloodspot Screening ◽  
The Uk ◽  
The Cost

Glutaric aciduria type 1, homocystinuria, isovaleric acidaemia, long-chain hydroxyacyl CoA dehydrogenase deficiency and maple syrup urine disease are all inborn errors of metabolism that can be detected through newborn bloodspot screening. This evaluation was undertaken in 2013 to provide evidence to the UK National Screening Committee for the cost-effectiveness of including these five conditions in the UK Newborn Bloodspot Screening Programme. A decision-tree model with lifetable estimates of outcomes was built with the model structure and parameterisation informed by a systematic review and expert clinical judgment. A National Health Service/Personal Social Services perspective was used, and lifetime costs and quality-adjusted life years (QALYs) were discounted at 1.5%. Uncertainty in the results was explored using expected value of perfect information analysis methods together with a sensitivity analysis using the screened incidence rate in the UK from 2014 to 2018. The model estimates that screening for all the conditions is more effective and cost saving when compared to not screening for each of the conditions, and the results were robust to the updated incidence rates. The key uncertainties included the sensitivity and specificity of the screening test and the estimated costs and QALYs.

scholarly journals Abnormal TREC-Based Newborn Screening Test in a Premature Neonate with Massive Perivillous Fibrin Deposition of the Placenta

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Stefan Kostadinov ◽  
Karen A. Robbins ◽  
Anthony Hayward
Keyword(s):  
Newborn Screening ◽  
B Lymphocyte ◽  
Severe Combined Immunodeficiency ◽  
Male Infant ◽  
Cell Receptor ◽  
Premature Neonate ◽  
Fibrin Deposition ◽  
Thymic Involution ◽  
Real Time Quantitative Pcr ◽  
Excision Circles

Severe combined immunodeficiency (SCID), a primary immunodeficiency arising from variable defects in lymphocyte development and survival, is characterized by significant deficiency of thymus derived (T-) lymphocytes and variable defects in the B-lymphocyte population. Newborn screening for SCID is based on detection of low numbers of T-cell receptor excision circles (TRECs) by real time quantitative PCR (RT-qPCR). This screening allows for early identification of individuals with SCID and other disorders characterized by T-lymphopenia. Higher rates of abnormal screens are commonly seen in premature and critically ill neonates, often representing false positives. It is possible that many abnormal screens seen in these populations are result of conditions that are characterized by systemic inflammation or stress, possibly in the context of stress-induced thymic involution. We present a case of a male infant delivered at 27 weeks, 6 days of gestation, with severe intrauterine growth restriction who had an abnormal TREC screen and amassive perivillous fibrin deposition(MPFD) of the placenta. This association has not been reported previously. We are raising the awareness to the fact that conditions, such as MPFD, that can create adverse intrauterine environment are capable of causing severe stress-induced thymic involution of the fetus which can present with abnormal TREC results on newborn screening.

Sign in / Sign up

Export Citation Format

Share Document