scholarly journals Establishing Newborn Screening for SCID in the USA; Experience in California

2021 ◽  
Vol 7 (4) ◽  
pp. 72
Author(s):  
Jennifer M. Puck ◽  
Andrew R. Gennery
Keyword(s):  
Newborn Screening ◽  
Screening Program ◽  
Receptor Gene ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Dried Blood Spots ◽  
Infectious Complications ◽  
Serious Infections ◽  
The Usa ◽  
Excision Circles

Newborn screening for severe combined immunodeficiency (SCID) has developed from the realization that infants affected with SCID require prompt diagnosis and treatment to avoid fatal infectious complications. Screening DNA from infant dried blood spots for T-cell receptor excision circles (TRECs), byproducts of normal antigen-receptor gene rearrangement, has proven to be a reliable method to identify infants with SCID and other serious T lymphocyte defects before the onset of serious infections. The experience of the SCID newborn screening program in California after screening over 3 million infants demonstrates the effectiveness of this measure.

scholarly journals First Year of TREC-Based National SCID Screening in Sweden

2021 ◽  
Vol 7 (3) ◽  
pp. 59
Author(s):  
Christina Göngrich ◽  
Olov Ekwall ◽  
Mikael Sundin ◽  
Nicholas Brodszki ◽  
Anders Fasth ◽  
...  
Keyword(s):  
T Cell ◽  
Predictive Value ◽  
Screening Program ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Dried Blood Spots ◽  
First Year ◽  
Swedish Population ◽  
T Cell Lymphopenia ◽  
Excision Circles

Screening for severe combined immunodeficiency (SCID) was introduced into the Swedish newborn screening program in August 2019 and here we report the results of the first year. T cell receptor excision circles (TRECs), kappa-deleting element excision circles (KRECs), and actin beta (ACTB) levels were quantitated by multiplex qPCR from dried blood spots (DBS) of 115,786 newborns and children up to two years of age, as an approximation of the number of recently formed T and B cells and sample quality, respectively. Based on low TREC levels, 73 children were referred for clinical assessment which led to the diagnosis of T cell lymphopenia in 21 children. Of these, three were diagnosed with SCID. The screening performance for SCID as the outcome was sensitivity 100%, specificity 99.94%, positive predictive value (PPV) 4.11%, and negative predictive value (NPV) 100%. For the outcome T cell lymphopenia, PPV was 28.77%, and specificity was 99.95%. Based on the first year of screening, the incidence of SCID in the Swedish population was estimated to be 1:38,500 newborns.

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 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.

Newborn Screening through TREC, TREC/KREC system for Primary Immunodeficiency with limitation of TREC/KREC. Comprehensive review

2020 ◽  
Vol 19 ◽  
Author(s):  
Khyber Shinwari ◽  
Mikhail Bolkov ◽  
Irina A. Tuzankina ◽  
Valery Alexandrovich CHERESHNEV
Keyword(s):  
T Cell ◽  
Newborn Screening ◽  
T Cell Receptor ◽  
Case Series ◽  
Cell Receptor ◽  
The United States ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Different Types ◽  
Excision Circles

Introduction: Newborn screening (NBS) by quantifying T cell receptor excision circles (TRECs) and Kappa re-ceptor excision circles in neonatal dried blood spots (DBS) enables early diagnosis of different types of primary immune deficiencies. Global newborn screening for PID, using an assay to detect T-cell receptor excision circles (TREC) in dried blood spots (DBS), is now being performed in all states in the United States. In this review, we discuss the development and outcomes of TREC, TREC/KREC combines screening, and continued challenges to implementation. Objective: To review the diagnostic performance of published articles for TREC and TREC/ KREC based NBS for PID and its different types. Methods: Different research resources were used to get an approach for the published data of TREС and KREC based NBS for PID like PubMed, Scopus, Google Scholar, Research gate EMBASE. We extracted TREC and KREC screening Publisher with years of publication, content and cut-off values, and a number of retests, repeat DBS, and referrals from the different published pilot, pilot cohort, Case series, and cohort studies. Results: We included the results of TREC, combine TREC/KREC system based NBS screening from different research articles,and divided these results between the Pilot studies, case series, and cohort. For each of these studies, different parameter data are excluded from different articles. Thirteen studies were included, re-confirming 89 known SCID cases in case series and reporting 53 new SCID cases in 3.15 million newborns. Individual TREC contents in all SCID patients were <25 TRECs/μl (except in those evaluated with the New York State assay). Conclusion: TREC and KREC sensitivity for typical SCID and other types of PID was100 %. It shows its importance and anticipating the significance of implementation in different undeveloped and developed countries in the NBS program in upcoming years. Data adapting the screening algorithm for pre-term/ill infants reduce the amount of false-positive test re-sults.

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.

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