PURPOSE: Severe Combined Immunodeficiency (SCID) is considered to be a paediatric emergency and unless identified promptly can be life-threatening. Frequently, infants are not diagnosed with SCID until they have become seriously ill with infection leading to treatment complications and a poorer prognosis. We aimed to test a newly available commercial duplex assay to measure T cell receptor excision circles (TRECs) to establish if this would be suitable for newborn screening for SCID in the UK. METHODS: Over 5000 anonymous retrospective dried blood spots (DBS) were used alongside 18 confirmed SCID positive DBS with a newly available duplex assay to measure TRECs levels and control gene levels. We also included testing of premature babies and babies from neonatal intensive care units (NICU) as these have been shown to have high false positive rates in other TREC screening assays. RESULTS: All 18 SCID DBS samples were successfully identified as SCID positives in the study. The number of presumptive positives detected was dependent on the TREC cut-off threshold settings. When analysed with five different TRECs cut-off values (20, 25, 30, 35 and 40 TREC copies/μl blood) the presumptive positive rate ranged from 0.04 to 1.00 % of samples tested. Premature infants and neonates from NICU did not show high presumed false positive rates in this assay. CONCLUSIONS: The study demonstrated that this duplex assay kit will identify all newborns with SCID as presumptive positives. The data also shows that with suitable TREC cut-off settings the number of presumptive positives from non-SCID newborns will be manageable in the context of a national screening service.
PURPOSE: Severe Combined Immunodeficiency (SCID) is considered to be a paediatric emergency and unless identified promptly can be life-threatening. Frequently, infants are not diagnosed with SCID until they have become seriously ill with infection leading to treatment complications and a poorer prognosis. We aimed to test a newly available commercial duplex assay to measure T cell receptor excision circles (TRECs) to establish if this would be suitable for newborn screening for SCID in the UK. METHODS: Over 5000 anonymous retrospective dried blood spots (DBS) were used alongside 18 confirmed SCID positive DBS with a newly available duplex assay to measure TRECs levels and control gene levels. We also included testing of premature babies and babies from neonatal intensive care units (NICU) as these have been shown to have high false positive rates in other TREC screening assays. RESULTS: All 18 SCIDDBS samples were successfully identified as SCID positives in the study. The number of presumptive positives detected was dependent on the TREC cut-off threshold settings. When analysed with five different TRECs cut-off values (20, 25, 30, 35 and 40 TREC copies/μl blood) the presumptive positive rate ranged from 0.04 to 1.00 % of samples tested. Premature infants and neonates from NICU did not show high presumed false positive rates in this assay. CONCLUSIONS: The study demonstrated that this duplex assay kit will identify all newborns with SCID as presumptive positives. The data also shows that with suitable TREC cut-off settings the number of presumptive positives from non-SCID newborns will be manageable in the context of a national screening service.
Authors: Lucinda Brown; Jinhua Xu-Bayford; Zoe Allwood; Mary Slatter; Andrew Cant; E Graham Davies; Paul Veys; Andrew R Gennery; H Bobby Gaspar Journal: Blood Date: 2011-01-27 Impact factor: 22.113
Authors: Jacalyn L Gerstel-Thompson; Jonathan F Wilkey; Jennifer C Baptiste; Jennifer S Navas; Sung-Yun Pai; Kenneth A Pass; Roger B Eaton; Anne Marie Comeau Journal: Clin Chem Date: 2010-07-21 Impact factor: 8.327
Authors: James W Verbsky; Mei W Baker; William J Grossman; Mary Hintermeyer; Trivikram Dasu; Benedetta Bonacci; Sreelatha Reddy; David Margolis; James Casper; Miranda Gries; Ken Desantes; Gary L Hoffman; Charles D Brokopp; Christine M Seroogy; John M Routes Journal: J Clin Immunol Date: 2011-11-10 Impact factor: 8.317
Authors: Sean A McGhee; E Richard Stiehm; Morton Cowan; Paul Krogstad; Edward R B McCabe Journal: Mol Genet Metab Date: 2005-11-02 Impact factor: 4.797
Authors: Antonia Kwan; Joseph A Church; Morton J Cowan; Rajni Agarwal; Neena Kapoor; Donald B Kohn; David B Lewis; Sean A McGhee; Theodore B Moore; E Richard Stiehm; Matthew Porteus; Constantino P Aznar; Robert Currier; Fred Lorey; Jennifer M Puck Journal: J Allergy Clin Immunol Date: 2013-07 Impact factor: 10.793
Authors: Mei W Baker; William J Grossman; Ronald H Laessig; Gary L Hoffman; Charles D Brokopp; Daniel F Kurtycz; Michael F Cogley; Thomas J Litsheim; Murray L Katcher; John M Routes Journal: J Allergy Clin Immunol Date: 2009-05-31 Impact factor: 10.793
Authors: Waleed Al-Herz; Aziz Bousfiha; Jean-Laurent Casanova; Helen Chapel; Mary Ellen Conley; Charlotte Cunningham-Rundles; Amos Etzioni; Alain Fischer; Jose Luis Franco; Raif S Geha; Lennart Hammarström; Shigeaki Nonoyama; Luigi Daniele Notarangelo; Hans Dieter Ochs; Jennifer M Puck; Chaim M Roifman; Reinhard Seger; Mimi L K Tang Journal: Front Immunol Date: 2011-11-08 Impact factor: 7.561
Authors: Marie A P Audrain; Alexandra J C Léger; Caroline A F Hémont; Sophie M Mirallié; David Cheillan; Marie G M Rimbert; Aurélie M-P Le Thuaut; Véronique A Sébille-Rivain; Aurore Prat; Enora M Q Pinel; Eléonore Divry; Cécile G L Dert; Maxime A G Fournier; Caroline J C Thomas Journal: J Clin Immunol Date: 2018-09-24 Impact factor: 8.317
Authors: Maartje Blom; Rolf H Zetterström; Asbjørg Stray-Pedersen; Kimberly Gilmour; Andrew R Gennery; Jennifer M Puck; Mirjam van der Burg Journal: J Allergy Clin Immunol Date: 2021-09-16 Impact factor: 14.290
Authors: Ashleigh R Pavey; Dale L Bodian; Thierry Vilboux; Alina Khromykh; Natalie S Hauser; Kathi Huddleston; Elisabeth Klein; Aaron Black; Megan S Kane; Ramaswamy K Iyer; John E Niederhuber; Benjamin D Solomon Journal: Genet Med Date: 2017-06-15 Impact factor: 8.822
Authors: Jet van der Spek; Rolf H H Groenwold; Mirjam van der Burg; Joris M van Montfrans Journal: J Clin Immunol Date: 2015-04-17 Impact factor: 8.317