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Prospective neonatal screening for severe T‐ and B‐lymphocyte deficiencies in Seville
Author(s) -
Felipe Beatriz,
Olbrich Peter,
Lucenas José Manuel,
DelgadoPecellin Carmen,
PavonDelgado Antonio,
Marquez Josefina,
Salamanca Carmen,
SolerPalacin Pere,
GonzalezGranado Luis Ignacio,
Antolin Laura Ferreras,
Borte Stephan,
Neth Olaf
Publication year - 2016
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12501
Subject(s) - medicine , severe combined immunodeficiency , newborn screening , immunodeficiency , pediatrics , prospective cohort study , gastroenterology , immunology , immune system , gene , biochemistry , chemistry
Abstract Background Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency ( SCID ) and X‐linked agammaglobulinemia ( XLA ) improves outcome of affected children. T‐cell‐receptor‐excision circles ( TREC s) and kappa‐deleting‐recombination‐excision circles ( KREC s) determination from dried blood spots ( DBS ) identify neonates with severe T‐ and/or B‐lymphopenia. No prospective data exist of the impact of gestational age ( GA ) and birth weight ( BW ) on TREC s and KREC s values. Methods TREC s and KREC s determination using triplex RT ‐ PCR ( TRECS ‐ KRECS ‐β‐actin‐Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut‐off levels were TREC s < 6/punch, KREC s < 4/punch and ‐β‐actin>700/punch. Internal ( SCID , XLA , ataxia telangiectasia) and external controls ( NBS quality assurance program, CDC ) were included. Results A total of 5160 DBS were tested. Re‐punch was needed in 77 samples (1.5%) due to insufficient β‐actin (<700 copies/punch). Pre‐term neonates ( GA <37 weeks) and neonates with a BW <2500 g showed significantly lower TREC s and KREC s levels (p < 0.001). Due to repeat positive results five neonates were re‐called (<0.1%): Fatal chromosomopathy (n = 1; TREC s 1/ KREC s 4); extreme pre‐maturity (n = 2; TREC s 0/ KREC s 0 and TREC s 1/ KREC s 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TREC s 92/ KREC s 1 and TREC s 154/ KREC s 3 copies/punch). All internal and external controls were correctly identified. Conclusions TRECS ‐ KRECS –β‐actin‐Assay correctly identifies T‐ and B‐cell lymphopenias. Pre‐maturity and low BW is associated with lower TREC and KREC levels. Extreme pre‐maturity and maternal immune suppressive therapy may be a cause for false positive results of TREC s and KREC s values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved.