T-cell receptor and K-deleting recombination excision circles in newborn screening of T- and B-cell defects : review of the literature and future challenges

Since its introduction as a public health programme in the United
States in the early 1960s, newborn blood screening (NBS) has evolved
from the detection of phenylalanine levels on filter paper to the application
of DNA-based technologies to identify T-cell lymphopenia in
infants with severe combined immunodeficiency. This latter use of
NBS has required the development of an assay for T-cell lymphopenia
based on the quantification of T-cell receptor excision circles (TRECs)
that could be performed on dried blood spots routinely collected from
newborn infants. The TREC-based NBS was developed six years ago,
and there have already been 7 successful pilot studies since then.
Similarly, efforts are now being made to establish a screen for B-cell
defects, in particular agammaglobulinaemia, taking advantage of the
introduction of the method for the quantification of K-deleting recombination
excision circles (KRECs). A further achievement of NBS
could be the simultaneous recognition of T- and B-cell defects using
the combined quantification of TRECs and KRECs from Guthrie card
blood spots. This approach may help the early identification of infants
with T- and B-cell deficiencies so that they can then be referred to specialised
paediatric centres, where a precise diagnosis of severe combined
immunodeficiency and agammaglobulinaemia can be performed,
and where then they can immediately receive specific therapy.
Simultaneous TREC and KREC quantification should also allow classification
of patients into subgroups and help identify children with less
serious primary immunodeficiencies. This would help avoid the opportunistic
infections and frequent hospitalisations that result from a late
or lack of diagnosis.