Newborn screening for severe T and B cell immunodeficiency in Israel: a pilot study.
BACKGROUND
Enumeration of T cell receptor excision circles (TREC) was recently adopted as a neonatal screening assay for severe combined immunodeficiency (SCID). Enumeration of kappa-deleting recombination excision circle (KREC) copy numbers can be similarly used for early assessment of B cell lymphopenia.


OBJECTIVE
To assess the ability of TREC and KREC counts to identify patients with combined T and B cell immunodeficiency in a pilot study in Israel.


METHODS
We studied seven children born in Israel during the years 2010-2011 and later diagnosed with SCID, and an additional patient with pure B cell immunodeficiency. TREC and KREC in peripheral blood upon diagnosis and in their neonatal Guthrie cards were analyzed using real-time quantitative polymerase chain reaction, as were Guthrie cards with dried blood spots from healthy newborns and from normal and SCID-like controls.


RESULTS
The first features suggestive of SCID presented at age 3.1 +/- 2.4 months in all patients. Yet, the diagnosis was made 4.1 +/- 2.9 months later. Their TREC were undetectable or significantly low at their clinical diagnosis and in their originally stored Guthrie cards, irrespective of the amount of their circulating T cells. KREC were undetectable in six SCID patients who displayed B cell lymphopenia in addition to T cell lymphopenia. KREC were also undetectable in one patient with pure B cell immunodeficiency.


CONCLUSIONS
TREC and KREC quantification are useful screening tests for severe T and B cell immunodeficiency. Implementation of these tests is highly important especially in countries such as Israel where a high frequency of consanguinity is known to exist.
Cancer Research Center, Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel. raz.somech@sheba.health.gov.il
Raz
R
Somech
Atar
A
Lev
Amos J
AJ
Simon
David
D
Korn
Ben Zion
BZ
Garty
Ninette
N
Amariglio
Gideon
G
Rechavi
Shlomo
S
Almashanu
Joel
J
Zlotogora
Amos
A
Etzioni
D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D059788:Dried Blood Spot Testing; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007557:Israel; D015997:Neonatal Screening / Q000379:methods*; D010865:Pilot Projects; D060888:Real-Time Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors
D011948:Receptors, Antigen, T-Cell